Oil composition containing caproic acid residues, unsaturated fatty acid residues and saturated fatty acid residues

Abstract

The oil composition contains 1% to 20% by weight of caproic acid residues (C6:0), at least 55% by weight of C 16 -C 18 Unsaturated fatty acid residues and less than 40% by weight of C8-C 24 The percentage of fatty acid residues refers to fatty acids attached as acyl groups to glycerides in the oil composition, including saturated fatty acid residues, and includes saturated and unsaturated C4-C acyl fatty acid residues present in the oil composition. 24 At least 50% of the caproic acid residues present in the oil composition, based on the total weight of fatty acid residues, are present in triglycerides comprising at least one caproic acid residue and at least one fatty acid residue containing from 16 to 18 carbon atoms.

Description

[Technical Field]

[0001] The present invention relates to an oil composition and a nutritional product comprising said composition. The present invention also relates to a method for supplementing an individual's diet with said nutritional product and oil composition. [Background technology]

[0002] Short-chain fatty acids (SCFAs) are known to be desirable components of mammalian diets. Short-chain fatty acids are typically fatty acid molecules containing six or fewer carbon atoms. Examples of SCFAs include acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and caproic acid. SCFAs have been reported to be associated with various health and well-being benefits. For example, SCFAs have been associated with healthy gastrointestinal function and absorption, a healthy immune system, reduced chronic inflammation, and improved metabolism. Circulating SCFAs may also be associated with improved weight and appetite control, suggesting their potential use in obesity prevention. Blood SCFA levels have also been reported to be associated with blood glucose regulation and the prevention of insulin resistance, implying that SCFAs could potentially be used to prevent or ameliorate the onset of type 2 diabetes. Blaak et al., "Short-chain fatty acids in human gut and metabolic health," Beneficial Microbes, 2020; 11(5): 411-455, discloses that acetate, butyrate, and propionate may be involved in the pathophysiology of gastrointestinal health, obesity, and type 2 diabetes. Canfora et al., "Short-chain fatty acids in control of body weight and insulin sensitivity," Endocrinology, Volume 11, October 2015, also discusses the association of acetate, butyrate, and propionate with obesity and type 2 diabetes.

[0003] While SCFAs are generally known to be associated with the positive effects described above, the prior art has focused primarily on butyrate (C4:0), propionate (C3:0), and acetate (C2:0), with a primary focus on the in vivo effects of butyrate (C4:0). For example, Steliou et al., Butyrate Histone Deacetylase Inhibitors, BioResearch Open Access, Volume 1, Number 4, August 2012, discusses how butyrate acts as a histone deacetylase that could potentially be used to treat diet-induced obesity and prevent insulin resistance. Ivanov et al., The role of prenatal melatonin in the regulation of childhood obesity, Biology, 2020, 9, 72, discloses that butyrate can suppress obesity by its activity at the μ-opioid receptor. Lin et al., "Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms," Plos One, April 2012, Volume 7, Issue 4, e35240, discusses how butyrate and propionate protect against diet-induced obesity and insulin resistance, and that these SCFAs may have a significant impact on the treatment of type II diabetes and obesity. While the art has explored the potential and mechanisms of action of butyrate (and to a lesser extent propionate and acetate) as supplements to promote the health benefits mentioned above, caproic acid (C6:0) has not been the focus of previous research.

[0004] It is known in the art that when butyric acid is provided as an oral dietary supplement, it is undesirable to provide fatty acid in the form of free fatty acid, because butyric acid is degraded in the stomach and does not reach the systemic circulation that can promote the health benefits mentioned above.In addition, it is also undesirable to provide butyric acid in the form of salt, such as sodium butyrate, because it has an unpleasant taste, which means that it is not well accepted by consumers when taken orally.

[0005] To alleviate these problems, several attempts have been made to provide butyric acid in the form of plant-derived triglyceride oils. However, it has been found that providing butyric acid-containing triglyceride oils with sufficient organoleptic properties for oral consumption requires subjecting the plant-derived triglycerides to a deodorization process step to remove odorous compounds that impart an unpleasant odor, color, or taste to the triglycerides. Deodorization is a common process step in the refining of plant-derived triglyceride oils immediately after extraction from the plant source. The deodorization step typically involves subjecting the triglyceride oil to elevated temperatures of 100°C to 260°C under vacuum.

[0006] The inventors of the present invention have recognized that when deodorization of butyric acid-containing triglyceride oils (and even acetic acid-containing or propionic acid-containing triglyceride oils) is performed, a large amount of the triglyceride oil is lost during the deodorization step. During deodorization, the oil is typically heated to high temperatures. This heating process can cause triglycerides to evaporate, reducing the yield of the triglyceride oil deodorization process. This is undesirable when producing oils on a large scale, as the reduced yield negatively impacts the economics of the production process.

[0007] Thus, the inventors recognize that there remains a continuing need in the art for nutritional products for oral consumption that include triglyceride oil compositions that provide SCFAs to the systemic circulation and address the problems discussed above. [Prior art documents] [Non-patent literature]

[0008] [Non-Patent Document 1] Blaak et al., Short chain fatty acids in human gut and metabolic health, Beneficial Microbes, 2020; 11(5): 411-455 [Non-patent document 2] Canfora et al., Short-chain fatty acids in control of body weight and insulin sensitivity, Endocrinology, Volume 11, October 2015 [Non-patent document 3] Steliou et al., Butyrate Histone Deacetylase Inhibitors, BioResearch Open Access, Volume 1, Number 4, August 2012 [Non-patent document 4] Ivanov et al., The role of prenatal melatonin in the regulation of childhood obesity, Biology, 2020, 9, 72 [Non-Patent Document 5] Lin et al., Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms, Plos One, April 2012, Volume 7, Issue 4, e35240 Summary of the Invention [Means for solving the problem]

[0009] The present invention is based on the surprising discovery that certain triglyceride oil compositions address or alleviate the above-mentioned problems. Surprisingly, it has been found that certain triglyceride oil compositions containing caproic acid, after a deodorization step, have a higher yield than similar triglyceride compositions containing butyric acid instead of caproic acid. Without wishing to be bound by theory, this is believed to be due to the higher average molecular weight of the triglycerides containing caproic acid instead of the shorter-chain butyric acid. The higher average molecular weight of the triglycerides is believed to mean that the triglycerides are less likely to volatilize or be lost during the deodorization process step, which is important to ensure that the triglyceride oil has acceptable sensory properties. This allows certain oil compositions to be produced and deodorized in higher yields, resulting in improved economics for the manufacturing process. When caproic acid (C6:0) is delivered to the systemic circulation, it can also provide the same or similar health and well-being benefits as shorter-chain SCFCs such as butyric acid.

[0010] According to an embodiment of the present invention, 1% to 20% by weight of caproic acid residues (C6:0), at least 55% by weight of C 16 -C 18 Unsaturated fatty acid residues and less than 40% by weight of C8-C 24 an oil composition comprising saturated fatty acid residues, wherein the percentage of fatty acid residues refers to fatty acids attached as acyl groups to glycerides in the oil composition, and includes saturated and unsaturated C4-C acyl groups present in the oil composition; 24 An oil composition is provided wherein at least 50% of the caproic acid residues present in the oil composition, based on the total weight of fatty acid residues, are present in triglycerides comprising at least one caproic acid residue and at least one fatty acid containing from 16 to 18 carbon atoms.

[0011] The oil composition is a triglyceride oil composition. Typically, at least 50% of the fatty acid moieties present in the oil composition are present in triglyceride molecules. Preferably, at least 70%, more preferably at least 80%, even more preferably at least 90%, and most preferably at least 95% of the fatty acid moieties present in the oil composition are present in triglyceride molecules.

[0012] As used herein, the terms "fat" and "oil" are used interchangeably and refer to glyceride fats and oils containing fatty acyl groups and do not imply any particular melting point.

[0013] As used herein, the term "fatty acid" refers to a linear, saturated or unsaturated (including monounsaturated and polyunsaturated) carboxylic acid having 4 to 24 carbon atoms. A fatty acid having x carbon atoms and y double bonds may be represented as Cx:y. For example, palmitic acid may be represented as C16:0, and oleic acid may be represented as C18:1. The percentage of fatty acids in a composition referred to herein includes the acyl groups of triglycerides, diglycerides, and monoglycerides present in the glyceride, and includes C4-C 24 The fatty acid profile (i.e., composition) can be determined by fatty acid methyl ester analysis (FAME), for example, using gas chromatography according to ISO 16958.

[0014] As used herein, the terms "hexanoic acid" and "caproic acid" are used interchangeably to refer to a compound having the structural formula CH3CH2CH2CH2CH2(CO)OH. The oil composition preferably comprises caproic acid (C6:0) in an amount of 1% to 15% by weight, more preferably 1% to 10% by weight, and even more preferably 2% to 15% by weight. Most preferably, the oil composition comprises caproic acid (C6:0) in an amount of 2% to 10% by weight.

[0015] In some examples, the oil composition comprises 4% to 20% by weight, e.g., 4% to 15% by weight, of caproic acid. For example, the oil composition may comprise 4% to 10% by weight of caproic acid. In other examples, the oil composition comprises 5% to 20% by weight, e.g., 5% to 15% by weight of caproic acid. For example, the oil composition may comprise 5% to 10% by weight of caproic acid.

[0016] Typically, the oil composition comprises 2% to 30% by weight of butyric acid residues (C4:0). Preferably, the oil composition comprises butyric acid (C4:0) in an amount of 2% to 25% by weight, more preferably 2% to 20% by weight, and most preferably 2% to 15% by weight.

[0017] In another preferred embodiment, the oil composition comprises butyric acid (C4:0) residues in an amount of 7.5% to 30% by weight, preferably 7.5% to 25% by weight, more preferably 7.5% to 20% by weight, and most preferably 7.5% to 15% by weight.

[0018] In certain preferred examples, the oil composition comprises 4% to 20% by weight of caproic acid residues and 7.5% to 30% by weight of butyric acid residues, such as 4% to 10% by weight of caproic acid residues and 7.5% to 15% by weight of butyric acid residues.

[0019] Typically, at least 50% of the butyric acid residues present in the oil composition are present in triglycerides comprising at least one butyric acid residue and at least one fatty acid residue containing from 16 to 18 carbon atoms.

[0020] The advantage of including butyric acid in the composition along with caproic acid is that the composition can mimic and contain the same fatty acids present in animal-based dairy fats that are high in both caproic and butyric acid. Thus, the oil composition of the present invention can be used as a dairy fat replacement composition. Because the oil composition of the present invention is typically derived from a non-animal source, the composition can advantageously serve as a non-animal dairy fat substitute. Advantageously, the oil composition of the present invention contains a higher amount of unsaturated fatty acids and a lower amount of saturated fatty acids than dairy fats. Typically, the oil composition of the present invention also contains a lower amount of palmitic acid than dairy fats. This is advantageous in view of the negative health effects associated with consuming excessive amounts of saturated fat or excessive amounts of palmitic acid, which may adversely affect blood cholesterol levels.

[0021] Another advantage of including butyric acid residues in addition to caproic acid residues in the oil compositions of the present invention is that, as shown in the examples below, a surprising synergistic increase in the expression of the anti-inflammatory biomarker IL-10 was observed. It was found that the combination of caproic acid (C6:0) and butyric acid (C4:0) synergistically increased the expression levels of IL-10, which is associated with the amelioration and prevention of chronic inflammation and obesity.

[0022] Typically, the oil composition has a weight ratio of butyric acid residues (C4:0) to caproic acid residues (C6:0) of from 1:1 to 6:1, preferably from 1:1 to 4:1, more preferably from 1:1 to 2.5:1, and most preferably from 1:1 to 2:1.

[0023] In the oil composition, at least 50% of the caproic acid residues present in the oil composition are present in triglycerides comprising at least one caproic acid residue and at least one fatty acid residue containing 16 to 18 carbon atoms. A further advantage of the present invention is that it has surprisingly been found that including caproic acid residues in triglyceride molecules along with longer chain fatty acids having 16 to 18 carbon atoms advantageously delays cleavage of the caproic acid moiety from the triglyceride by lipases in the gastrointestinal tract until the triglyceride molecule is in the small intestine. It is also surprising that the inventors have found that triglycerides containing three SCFCs, such as three caproic acid residues, or mixtures of caproic and butyric acid residues, are degraded in the stomach by gastric lipase after oral ingestion. Cleavage of caproic acid from triglyceride molecules in the stomach is undesirable because, if this occurs, caproic acid will not reach the systemic circulation and instead be absorbed and metabolized by stomach cells that utilize caproic acid as an energy source. In this scenario, caproic acid will not reach the systemic circulation and will not be able to promote the beneficial health effects described above. In contrast, if cleavage of caproic acid from triglycerides is delayed until the small intestine, as in the compositions of the present invention, the free caproic acid residues are available for absorption in the small intestine and then enter the systemic circulation. The presence of fatty acid residues containing 16 to 18 carbon atoms in the triglyceride molecule along with the caproic acid residue is believed to inhibit the action of gastric lipase, which would otherwise cleave caproic acid from the triglyceride.

[0024] In the oil compositions of the present invention, it is particularly preferred that caproic and butyric acid residues, if present, are present in triglycerides containing two fatty acids containing 16 to 18 carbon atoms. It is believed that cleavage of caproic / butyric acid from the glycerol backbone of a triglyceride by gastric lipase is even more inhibited when the triglyceride contains two fatty acids containing 16 to 18 carbon atoms than when the triglyceride contains only one fatty acid residue containing 16 to 18 carbon atoms. The inclusion of such triglycerides in the composition may thus result in higher gastrointestinal absorption (and thus blood plasma concentrations) of short-chain fatty acids. This effect was observed in the Examples described below, where a composition containing a large amount of a triglyceride containing one caproic acid residue and two fatty acids having 16 to 18 carbon atoms increases postprandial caproic acid plasma concentrations more than a composition containing a small amount of the triglyceride overall, even though the composition contains a small amount of the triglyceride containing a large amount of caproic acid residues.

[0025] Typically, at least 60%, preferably at least 70%, more preferably at least 75% of the caproic acid residues present in the oil composition, and at least 60%, preferably at least 70%, more preferably at least 75% of the butyric acid residues present in the oil composition, are present in triglycerides comprising at least one butyric or caproic acid residue and at least one fatty acid containing from 16 to 18 carbon atoms.

[0026] Preferably, at least 80% of the caproic acid residues present in the oil composition and at least 80% of the butyric acid residues present in the oil composition are present in triglycerides comprising at least one butyric or caproic acid residue and at least one fatty acid containing from 16 to 18 carbon atoms.

[0027] Typically, at least 20%, preferably at least 25%, more preferably at least 30% of the caproic acid residues present in the oil composition, and at least 20%, preferably at least 25%, more preferably at least 30% of the butyric acid residues present in the oil composition, are present in triglycerides comprising a butyric or caproic acid residue and two fatty acid residues containing 16 to 18 carbon atoms.

[0028] In highly preferred examples, at least 25% of the caproic acid residues present in the oil composition and at least 25% of the butyric acid residues present in the oil composition are present in triglycerides comprising a butyric acid residue or a caproic acid residue and two fatty acid residues containing 16 to 18 carbon atoms. Even more preferably, at least 30% of the caproic acid residues present in the oil composition and at least 30% of the butyric acid residues present in the oil composition are present in triglycerides comprising a butyric acid residue or a caproic acid residue and two fatty acid residues containing 16 to 18 carbon atoms. In these particular examples, preferably, at least 70% of the caproic acid residues present in the oil composition and at least 70% of the butyric acid residues present in the oil composition are present in triglycerides comprising at least one butyric acid residue or a caproic acid residue and at least one fatty acid residue containing 16 to 18 carbon atoms.

[0029] In some examples, at least 50%, e.g., at least 60%, at least 70%, or at least 80% of the caproic acid residues present in the oil composition, and at least 50%, e.g., at least 60%, at least 70%, or at least 80% of the butyric acid residues present in the oil composition, are present in triglycerides comprising butyric or caproic acid residues and two fatty acid residues containing 16 to 18 carbon atoms.

[0030] In the oil compositions of the present invention, the percentage of caproic and / or butyric acid residues present in the oil composition is present in triglycerides containing one or two fatty acid residues having 16 to 18 carbon atoms and a butyric or caproic acid residue, as determined according to ISO 17383, modified to include triglycerides containing short chain fatty acids, using the following triglyceride standards for response factors: C12 (tributyrin), C18 (tricaproin), C24 (tricaprylin), C30 (tricaprin), C36 (trilaurin), C42 (trimyristin), C48 (tripalmitin), and C54 (tristearin).

[0031] Typically, the oil composition contains fatty acid residues having 16 to 18 carbon atoms in an amount of 60% to 95% by weight, preferably 65% ​​to 90% by weight, and more preferably 70% to 85% by weight. As mentioned above, it is important that the oil composition contains sufficient amounts of caproic and butyric acid residues, if present, so that most of these fatty acids are present in triglycerides containing at least one fatty acid moiety having 16 to 18 carbon atoms, such that cleavage of the caproic / butyric acid moiety by gastric lipase is inhibited. Typically, the oil composition has a weight ratio of fatty acid residues having 16 to 18 carbon atoms to butyric acid residues (C4:0) and caproic acid residues (C6:0) of 1:1 to 20:1, preferably 1.5:1 to 10:1, more preferably 2:1 to 7:1, and most preferably 2:1 to 6:1.

[0032] Typically, the majority of the fatty acid moieties having 16 to 18 carbon atoms present in the oil composition are unsaturated fatty acid moieties. This is advantageous because unsaturated fatty acids are generally considered healthier than saturated fatty acids. A diet excessively high in saturated fatty acids is associated with the development of heart disease and unhealthy cholesterol levels. An advantage of the oil composition of the present invention over dairy fat is that it contains much lower levels of saturated fatty acids and much higher levels of unsaturated fatty acids. A further advantage of containing more unsaturated fatty acids is that the oil composition of the present invention tends to have a lower melting point than compositions with a higher saturated fatty acid content. This can mean that the oil composition of the present invention is easier to incorporate into liquid dietary supplements (e.g., dietary supplement beverages) and is more palatable and organoleptically acceptable to consumers. Thus, typically, the oil composition contains C 16 -C 18 It contains unsaturated fatty acid residues in an amount of at least 60% by weight, preferably 65 to 92% by weight, more preferably 70 to 85% by weight, and most preferably 75 to 85% by weight.

[0033] Typically, the oil composition contains a total of 10% to 40% by weight of saturated fatty acid residues, preferably a total of 15% to 40% by weight of saturated fatty acid residues, more preferably a total of 15% to 30% by weight of saturated fatty acid residues.

[0034] As previously mentioned, the oil composition contains less than 40% by weight of C8-C 24 Preferably, the oil composition contains less than 35 wt. % C8-C9 saturated fatty acid residues, more preferably less than 30 wt. % C8-C9 saturated fatty acid residues, and most preferably less than 20 wt. % C8-C9 saturated fatty acid residues. 24 Contains saturated fatty acid residues.

[0035] Typically, the oil composition contains no more than 10% by weight of palmitic acid (C16:0), preferably no more than 8% by weight, more preferably no more than 6% by weight, and most preferably no more than 4% by weight. Like saturated fatty acids, palmitic acid (C16:0) is considered to be more harmful to health than other saturated fatty acids, such as stearic acid (C18:0). Therefore, it is desirable that the oil composition not contain excessive amounts of palmitic acid. Palmitic acid is also a major component of palm oil, and palm oil-derived products often have a high palmitic acid content. Due to public awareness of the environmental impact of palm oil production, it is preferred that the oil composition of the present invention is not derived from palm oil.

[0036] Of the fatty acid residues containing 16 to 18 carbon atoms present in the oil composition, it is preferred that most of these fatty acids are fatty acids with 18 carbon atoms. Fatty acids with 18 carbon atoms are believed to inhibit the cleavage of caproic acid and butyric acid from triglycerides by gastric lipase more effectively than fatty acids with 16 or 17 carbon atoms. In addition, because fatty acids with 17 carbon atoms are generally not readily produced in plant-derived triglyceride oils, if the oil composition is derived from a plant-derived oil, such as a vegetable oil, the oil composition will typically have a very low content of fatty acids with 17 carbon atoms. Therefore, the oil composition typically contains a total of 10 wt. % or less, preferably 7 wt. % or less, and more preferably 5 wt. % or less, of fatty acid residues containing 16 or 17 carbon atoms.

[0037] Therefore, the oil composition has a very high content of fatty acids with 18 carbon atoms, more preferably unsaturated C 18A very high fatty acid content is preferred. Typically, the oil composition contains 50% to 90% by weight of oleic acid (C18:1) residues, preferably 56% to 85% by weight, and more preferably 56% to 76% by weight of oleic acid (C18:1) residues. Typically, the oil composition contains 1% to 25% by weight of linoleic acid (C18:2) residues, preferably 1% to 10% by weight, more preferably 2% to 9% by weight, and most preferably 4% to 9% by weight of linoleic acid (C18:2) residues. However, the oil composition preferably has a low content of saturated fatty acid residues, and therefore typically contains 10% by weight or less, preferably 8% by weight or less, more preferably 6% by weight or less, and most preferably 4% by weight or less of stearic acid (C18:0) residues.

[0038] Because oleic acid is more oxidatively stable than more unsaturated fatty acids, the oil composition contains more oleic acid (C18:1) than more unsaturated fatty acids such as linoleic acid (C18:2). It is preferable.

[0039] The oil composition is preferably a non-hydrogenated oil composition, more preferably a non-hydrogenated non-animal-derived oil composition such as a plant-derived composition or a microbial-derived composition. The oil composition has not been subjected to hydrogenation, and preferably none of the fatty acid moieties present in the oil composition have been subjected to hydrogenation, since the hydrogenation process increases the amount of trans-unsaturated fatty acids present. Trans-unsaturated fatty acids are associated with negative health effects in consumers. Therefore, preferably, the oil composition contains less than 5% by weight of trans-unsaturated fatty acids, more preferably less than 3% by weight of trans-unsaturated fatty acids, and most preferably less than 1% by weight of trans-unsaturated fatty acids.

[0040] Preferably, the oil composition is non-animal or at least partially non-animal derived.

[0041] Typically, at least 50% of the fatty acid residues present in the oil composition are of non-animal origin, such as plant and / or microbial origin, preferably at least 70%, more preferably at least 90% of the fatty acid residues present in the oil composition are of non-animal origin, such as plant and / or microbial origin, and most preferably, all of the fatty acid residues present in the oil composition are of non-animal origin, such as plant and / or microbial origin.

[0042] When the fatty acid residues present in an oil composition are both microbial and plant-derived, certain fatty acids may originate from plant sources and certain fatty acids may originate from microbial sources, and esterification of these fatty acids with glycerol can then form an oil composition in which all fatty acids present are plant-derived or microbial-derived.

[0043] Thus, the terms "plant-derived" or "microbial-derived" as used herein in the context of fatty acid residues present in an oil composition are used to refer to the origin of the fatty acids present as part of the triglycerides in the oil composition. For example, for an oil composition produced by chemical esterification, if all of the fatty acids present in the oil composition originate from vegetable oils, then all of the fatty acids present in the oil composition are encompassed by the term plant-derived, even if the final oil composition is prepared by a chemical reaction.

[0044] Typically, at least 50% of the glycerol backbones of the triglycerides present in the oil composition are of non-animal origin, such as plant and / or microbial origin, preferably at least 70%, more preferably at least 90% of the glycerol backbones of the triglycerides present in the oil composition are of non-animal origin, such as plant and / or microbial origin, and most preferably, all of the glycerol backbones of the triglycerides present in the oil composition are of non-animal origin, such as plant and / or microbial origin.

[0045] The oil compositions of the present invention can be prepared by any suitable method known in the art. For example, the oil compositions or components thereof may be prepared by interesterification, transesterification, or esterification using process conditions suitable for these reactions known in the art.

[0046] In the case of esterification, oil compositions can be produced directly by reacting glycerol with appropriate free fatty acids in the desired ratios to produce the desired oil composition. For example, glycerol may be reacted with unsaturated fatty acids such as caproic acid, butyric acid, oleic acid, and any other fatty acids desired to be included in the oil composition. In a similar reaction, glycerol may be reacted with a mixture of esters. For example, glycerol may be reacted with an ester containing oleic acid and an ester containing caproic acid. Suitable reaction conditions required to obtain the desired product should be apparent to those skilled in the art having the benefit of this disclosure. For example, temperatures ranging from 30°C to 80°C are typically used when an enzymatic process is used, and higher temperatures are used when no enzyme is used. Suitable catalysts include enzymatic catalysts such as lipases or chemical catalysts.

[0047] In the case of transesterification, triglycerides, such as triglycerides containing oleic acid, may be transesterified with a mixture of free fatty acids, including caproic acid and butyric acid, if desired. Alternatively, triglycerides containing caproic acid and, optionally, butyric acid may be transesterified with free fatty acids, including, for example, oleic acid. Transesterification also includes the reaction of triglycerides with non-glyceride esters, such as the reaction of an oleic acid-containing ester with a caproic acid-containing triglyceride, or the reaction of a caproic acid-containing ester with an oleic acid-containing triglyceride. After the transesterification reaction is performed, any free fatty acid by-products can be separated from the triglyceride component by distillation. Suitable reaction conditions required to obtain the desired product will be apparent to those skilled in the art having the benefit of this disclosure. Typically, temperatures between 30°C and 80°C are used, and enzymatic catalysts, such as regioselective or non-regioselective lipases, are used.

[0048] In interesterification, two triglyceride oils are mixed together and reacted to rearrange which fatty acid residues are attached to which glycerol molecules to form different triglyceride molecules. For example, a caproic acid-rich triglyceride, optionally containing butyric acid, may be interesterified with an oleic acid-rich triglyceride. The appropriate reaction conditions required to obtain the desired product will be apparent to one of skill in the art having the benefit of this disclosure, and can be found, for example, in Dijkstra, AJ Interesterification, The Lipids Handbook 3 rd Edition, pages 285-300 (F.D. Gunstone, J.L. Harwood, and A.J. Dijkstra (eds.), Taylor & Francis Group LLC, Boca Raton, FL) (2007). Typically, either a chemical catalyst such as sodium methylate or an enzymatic catalyst such as a regioselective or non-regioselective lipase can be used. Temperatures between 30°C and 100°C are typically used.

[0049] In a particular example, the oil composition comprises an interesterified blend comprising (a) a vegetable oil selected from sunflower oil, rapeseed oil, canola oil, safflower oil, soybean oil, algae oil, olive oil, high oleic acid versions thereof, or mixtures thereof, and (b) a triglyceride oil comprising at least 10% by weight of caproic acid residues, whereby the vegetable oil in (a) has a high oleic acid content, and thus the interesterified product comprises both caproic acid residues and oleic acid residues.

[0050] Preferably, triglyceride oil (b) contains at least 20% by weight of caproic acid residues. In some examples, triglyceride oil (b) may contain a very high amount of caproic acid, for example, at least 80% by weight or at least 90% by weight of caproic acid residues. For example, triglyceride oil (b) may contain tricaproin.

[0051] In instances where it is desired to include both caproic acid and butyric acid in the oil composition, oil (b) typically contains at least 90% by weight of caproic acid and butyric acid residues. For example, oil (b) may contain 20% to 40% by weight of caproic acid residues. Preferably, triglyceride oil (b) contains 20% to 40% by weight of caproic acid residues and 60% to 80% by weight of butyric acid residues. Triglyceride oil (b) can be obtained, for example, by esterification. In some instances, triglyceride oil (b) is derived from a microorganism, for example, obtained by a microbial fermentation process. For example, triglyceride oil (b) may contain triglycerides containing both caproic acid and butyric acid. Alternatively, or in addition, triglyceride oil (b) may contain a blend of caproic acid-rich triglycerides and butyric acid-rich triglycerides. For example, the triglyceride oil (b) may contain a mixture of tricaproin and tributyrin.

[0052] In the above example, the interesterified blend is typically an interesterified blend of 60% to 95% by weight of vegetable oil (a) and 5% to 40% by weight of triglyceride oil (b).

[0053] In certain examples where the above-described processes are used to provide oil compositions of the present invention, the oil composition further comprises a vegetable oil component (c) that is not produced by interesterification, transesterification, or esterification, preferably wherein the vegetable oil component (c) comprises sunflower oil, rapeseed oil, canola oil, safflower oil, soybean oil, algae oil, olive oil, high oleic acid versions thereof, or mixtures thereof. In these examples, preferably, the vegetable oil component (c) is present in the oil composition in an amount of 1% to 35% by weight, and the interesterified blend is present in the oil composition in an amount of 65% to 99% by weight.

[0054] After the oil composition of the present invention is produced, the oil composition is typically refined in the usual manner for plant-derived oils using refining processes known in the art. For example, the oil composition may be distilled, bleached, and / or deodorized using methods generally known in the art. One or more of distillation, bleaching, and / or deodorization may be performed. Preferably, all of these steps are performed, and more preferably, distillation is performed first, followed by bleaching and deodorization. Distillation is typically used to remove low-boiling components, such as free fatty acids, from the composition. Bleaching is performed to remove pigmentation from the composition and to increase the composition's organoleptic acceptability. Plant-derived compositions typically contain many pigments used to impart the color of the plant from which the composition is derived. Deodorization is performed to remove compounds that impart an unpleasant taste and / or odor to the composition. A preferred deodorization process is described in more detail below.

[0055] Preferably, the oil composition is a deodorized oil composition or includes deodorized components. For example, in some instances, the entire oil composition may be subjected to deodorization. In other instances, the components of the oil composition (e.g., the interesterified blends described above) may be deodorized and mixed with non-deodorized oil. In yet another instance, all of the components of the oil composition may be deodorized separately before being mixed together to form the oil composition.

[0056] As previously mentioned, deodorization of plant-derived oils is important for providing compositions that are organoleptically acceptable to consumers of nutritional products containing the oil composition. Also, as previously mentioned, the inventors have discovered that deodorization of an oil composition containing caproic acid residues results in a higher yield of deodorized composition than when a similar composition that does not contain caproic acid residues but instead contains shorter-chain fatty acids is deodorized. As used in this context, the term "analogous" refers to an oil composition that is identical except that, instead of containing caproic acid residues, it contains an equal weight percentage amount of shorter-chain fatty acids, such as acetic acid, propionic acid, or butyric acid. To achieve this improved deodorization process step yield, it is preferred that the caproic acid residues be present in the oil composition as higher molecular weight triglycerides (e.g., triglycerides having one or two longer-chain fatty acid residues and one caproic acid residue).

[0057] According to a second aspect of the present invention, there is provided a nutritional supplement comprising an oil composition according to the first aspect of the present invention.

[0058] As used herein, the term "dietary supplement" is used to refer to any product intended for oral consumption that is intended to be a medically or nutritionally functional food or supplement. Preferably, the dietary supplement is a food, an infant formula, or a supplement such as a tablet or capsule.

[0059] The nutritional supplement may include the oil composition in any suitable amount, typically in an amount of from 0.5% to 100% by weight of the oil composition.

[0060] In some cases, the nutritional supplement is liquid. For example, the nutritional supplement may be a beverage, yogurt, or cream. Additional ingredients of these products other than the oil composition, as well as suitable amounts of these additional ingredients to be included in the product, should be apparent to those skilled in the art with the benefit of this disclosure. Typically, when the nutritional supplement is a liquid product, the product contains the oil composition in an amount of 0.5% to 10% by weight.

[0061] In other examples, the dietary supplement is in a solid form, such as a powder tablet, dough, bar, or capsule. Additional ingredients of these products other than the oil composition, as well as suitable amounts of these additional ingredients to be included in the product, should be apparent to one of ordinary skill in the art given the benefit of this disclosure. Typically, when the dietary supplement is a solid product, the product contains the oil composition in an amount of 5% to 100% by weight.

[0062] The nutritional supplement product may contain the oil composition in any suitable amount, and typically the product will contain the oil composition in an amount comprising a total of 100 mg to 5000 mg of butyric acid residues and caproic acid residues, preferably 500 mg to 2500 mg, more preferably 750 mg to 1750 mg, and most preferably 1000 mg to 1750 mg.

[0063] Typically, the product will contain the oil composition in an amount comprising a total of 100mg to 5000mg of butyric acid residues per serving, preferably 500mg to 2500mg per serving, more preferably 750mg to 1750mg per serving, and most preferably 1000mg to 1750mg per serving of butyric acid residues and caproic acid residues.

[0064] Typically, the product will contain the oil composition in an amount containing 100mg to 1000mg, preferably 200mg to 700mg, more preferably 250mg to 650mg, most preferably 300mg to 600mg of caproic acid residues.

[0065] Typically, the product comprises the oil composition in an amount comprising 100mg to 1000mg of caproic acid residues per serving, preferably 200mg to 700mg per serving, more preferably 250mg to 650mg per serving, and most preferably 300mg to 600mg per serving.

[0066] It is highly preferred that the dietary supplement comprises the oil composition in an amount comprising a total of 1200 mg to 1600 mg, e.g., 1200 mg to 1600 mg, of butyric acid and caproic acid residues per serving, and it is highly preferred that the dietary supplement comprises the oil composition in an amount comprising 250 mg to 650 mg, e.g., 250 mg to 600 mg, of caproic acid residues per serving.

[0067] According to a third aspect of the present invention there is provided a non-therapeutic method of supplementing the diet of an individual comprising administering to the individual an oil composition according to the first aspect of the invention or a dietary supplement product according to the second aspect of the invention.

[0068] As previously mentioned, providing short chain fatty acids into the systemic circulation has been associated with a variety of health and well-being benefits in individuals.

[0069] In some examples, the method includes maintaining or improving gastrointestinal function in the individual, maintaining or improving immune system function in the individual, maintaining or improving small intestinal absorption in the individual, such as postprandial small intestinal absorption, maintaining or improving blood absorption in the individual, such as postprandial blood absorption, or regulating blood glucose levels in the individual, e.g., maintaining or improving ... -1 the individual, preventing or ameliorating diet-induced weight gain in the individual, preventing or ameliorating chronic inflammation in the individual, preventing or ameliorating insulin resistance in the individual, and / or maintaining or improving postprandial substrate and energy metabolism in the individual.

[0070] Typically, the method comprises administering to the individual an amount of the oil composition such that the oil composition provides the individual with a total daily amount of butyric acid residues of between 100 mg and 5000 mg, preferably between 500 mg and 2500 mg, more preferably between 750 mg and 1750 mg, and most preferably between 1000 mg and 1750 mg, of butyric acid residues, preferably the daily amount is provided in a single dose.

[0071] Most preferably, the method comprises administering to the individual an oil composition in an amount such that the oil composition provides the individual with a total daily amount of between 1200 mg and 1600 mg of butyric acid residues and caproic acid residues, preferably the daily amount is provided in a single serving.

[0072] Preferably, the method comprises administering to the individual an oil composition in an amount such that the oil composition provides the individual with a daily amount of caproic acid residues of between 100 mg and 1000 mg, preferably between 200 mg and 700 mg, more preferably between 250 mg and 650 mg, and most preferably between 300 mg and 600 mg, preferably the daily amount is provided in a single dose.

[0073] According to a fourth aspect of the present invention, there is provided use of a triglyceride comprising at least one fatty acid residue containing 16 to 18 carbon atoms and at least one caproic acid residue for increasing transport of caproic acid from the gastrointestinal tract to the systemic circulation.

[0074] As previously mentioned, it has surprisingly been found that when caproic acid is included in a triglyceride molecule with fatty acid residues containing 16 to 18 carbon atoms, the fatty acids containing 16 to 18 carbon atoms inhibit the action of gastric lipase, which is present in the stomach and cleaves caproic acid into glycerol bonds. As a result, triglycerides pass through the digestive tract, where they are degraded by intestinal lipase. The caproic acid residues are cleaved from triglycerides in the small intestine and then absorbed by the small intestine and enter the systemic circulation. This does not occur (or at least occurs less frequently) when caproic acid is cleaved from triglycerides in the stomach by gastric lipase because these caproic acid residues are absorbed by stomach cells and utilized for energy without entering the systemic circulation. When triglycerides contain only caproic acid and other short-chain fatty acids, the action of gastric lipase is not inhibited, and the caproic acid residues are cleaved from triglycerides in the stomach and do not reach the systemic circulation where they are thought to be necessary for their health-promoting effects. As such, the oil compositions of the present invention improve the transport of caproic acid into the systemic circulation over compositions containing only short chain triglycerides.

[0075] Thus, the use includes the use of triglycerides to increase the absorption of caproic acid by the small intestine, and the use of fatty acid residues containing 16 to 18 carbon atoms to inhibit the cleavage of caproic acid residues from triglycerides by gastric lipase.

[0076] Preferably, the triglyceride comprises at least one fatty acid residue having 18 carbon atoms, more preferably the triglyceride comprises at least one oleic acid residue or linoleic acid residue.

[0077] Preferably, the triglyceride comprises fatty acid residues having 16 to 18 carbon atoms.

[0078] Preferably, triglycerides are a component of the fat composition according to the first aspect of the invention.

[0079] According to a fifth aspect of the present invention, (a) providing an oil composition according to a first aspect of the present invention; and (b) deodorizing the oil composition to provide a deodorized oil composition. There is provided a method for deodorizing an oil composition according to the first aspect of the present invention, comprising:

[0080] Preferably, the oil composition of (a) is not pre-deodorized or contains at least one component that is not pre-deodorized.

[0081] Any suitable deodorizing conditions known in the art may be used.

[0082] Preferably, step (b) comprises carrying out a deodorization step at a temperature between 100°C and 200°C, more preferably between 130°C and 170°C, most preferably between 140°C and 160°C.

[0083] Preferably, the deodorization step is carried out at a pressure of from 0.5 mbar to 8 mbar, more preferably from 1 mbar to 6 mbar, most preferably from 1.5 mbar to 3 mbar. [Brief explanation of the drawings]

[0084] [Figure 1] FIG. 1 shows plasma concentrations of butyric acid residues (C4:0) after consumption of various inventive oil compositions and a control composition. [Figure 2] FIG. 1 shows plasma concentrations of caproic acid residues (C6:0) after consumption of various inventive oil compositions and a control composition. [Figure 3] FIG. 1 shows plasma concentrations of GLP-1 after consumption of various inventive oil compositions and a control composition. [Figure 4] FIG. 1 shows plasma concentrations of glucose after consumption of various inventive oil compositions and a control composition. [Figure 5] FIG. 1 shows plasma concentrations of insulin after consumption of various inventive oil compositions and a control composition. [Figure 6] FIG. 1 shows plasma concentrations of TNF-α after consumption of various inventive oil compositions and a control composition. [Figure 7] FIG. 1 shows plasma concentrations of IFN-γ after consumption of various oil compositions of the present invention and a control composition. [Figure 8] 1 shows the effect of different concentrations of butyrate on IL-6 production by stem cell-derived adipocytes treated with lipopolysaccharide (LPS), including a control condition without LPS stimulation. [Figure 9] 1 shows the effect of various concentrations of hexanoic acid on IL-6 production by stem cell-derived adipocytes treated with lipopolysaccharide (LPS). A control condition without LPS stimulation is included. [Figure 10] 1 shows the effect of hexanoic acid, butyric acid, and a combination of butyric acid and hexanoic acid on the expression of the cytokine IL-10 in stem cell-derived adipocytes treated with lipopolysaccharide (LPS), including conditions showing IL-10 expression without LPS stimulation. DETAILED DESCRIPTION OF THE INVENTION

[0085] The following examples are for illustrative purposes only and are not intended to limit the scope of the present invention in any way. [Example]

[0086] The bioaccessibility and absorption of three oil compositions, Oil Composition A, Oil Composition B, and Oil Composition C, was compared using the in vitro TIM-1 model, a computer-controlled dynamic model that mimics the human stomach, small intestine, and large intestine.

[0087] Oil composition A is a comparative composition not according to the invention and comprises triglycerides containing 71% by weight of butyric acid residues (C4:0) and 29% by weight of caproic acid residues (C6:0).

[0088] Oil composition B is in accordance with the present invention and is a blend of 8.5% by weight of oil composition A, 49.0% by weight of high oleic sunflower oil, and 42.5% by weight of rapeseed oil, containing 5.6% by weight of butyric acid residues (C4:0), 2.3% by weight of caproic acid residues (C6:0), and 68% by weight of oleic acid residues (C18:1) (as well as other fatty acids).

[0089] Oil Composition C is a comparative oil composition containing medium chain triglycerides (MCT) containing 59% by weight of octanoic acid residues (C8:0) and 41% by weight of decanoic acid (C10:0) residues. Oil Composition C is included as a reference composition for human absorption.

[0090] Table 1 shows the results of bioaccessibility and absorption in the human stomach, small intestine and large intestine. [Table 1] 1. Measured as the percentage of the respective fatty acid in free form that exits the gastric compartment of the total amount added (no absorption / metabolism mimicked in the gastric compartment). 2. Measured as the percentage of the total amount added that is in free form in the filtrate that passes through the semi-permeable membranes leading to the jejunal and ileal compartments (mimicking absorption in the small intestine). 3. Measured as the percentage of the respective fatty acid in free or bound form in the ileal effluent out of the total amount added. The residues remaining in the body correspond to the remainder when the sum of the amount absorbed in the small intestine and the amount that enters the large intestine is taken as 100%.

[0091] · Stomach The above results indicate that approximately 80-90% by weight of butyric acid residues (C4:0) and caproic acid residues (C6:0) are released in the stomach for Oil Composition A. In the human body, these free fatty acids are used for energy within stomach cells and do not reach the small intestine or circulation.

[0092] The results above indicate that for oil composition B, 7% of the butyric acid residues (C4:0) and 7% of the caproic acid residues (C6:0) were released from the glycerol backbone in the stomach. The remaining butyric and caproic acid residues remained bound to acylglycerides and were transported intact to the small intestine.

[0093] The above results show that for oil composition C, 40% of the medium chain fatty acids caprylic acid (C8:0) and 20% of capric acid (C10:0) are hydrolyzed in the stomach.

[0094] Gastric lipase activity is higher in oil composition A and oil composition C than in oil composition B. Oil composition C is a reference oil that demonstrates bioaccessibility and absorption of fatty acids in the human body. The presence of LCFA, i.e., oleic acid residues (C18:1) in oil composition B, is believed to reduce gastric lipase activity on the oil composition. Thus, most of the SCFA remains in the glycerol backbone and is later hydrolyzed and absorbed by the small intestine.

[0095] Small and large intestine The above results indicate that lipase in the small intestine can cleave caproic acid and butyric acid from the glycerol backbone in all of Oil Compositions A, B, and C in the small intestine.

[0096] Although it is suggested that after 5 hours, Oil Composition A has a higher weight percentage of caproic and butyric acid residues absorbed than Oil Composition B, this does not mean that Oil Composition A provides more caproic and butyric acid to the small intestine of the human body. For Oil Composition A, the caproic and butyric acid residues are hydrolyzed in the stomach before reaching the small intestine. The above model does not account for the fact that these free caproic and butyric acid residues can be used by stomach cells, and therefore only hydrolysis and not metabolism in the stomach is modeled.

[0097] For Oil Composition B, caproic acid and butyric acid may be cleaved from the glycerol backbone in the small intestine so that they can then be absorbed by the small intestine.

[0098] The bioavailability of oil composition B is similar to that of oil composition C. This means that most of the fatty acids in these compositions are released in the small intestine and can be absorbed into the circulation.

[0099] For all oil compositions, a small amount of fatty acids reaches the large intestine unuptaken and can be utilized by the microbiota or as an energy source for colonocytes.

[0100] The in vitro TIM-1 model shows that the SCFAs in Oil Composition A are primarily hydrolyzed in the stomach, rather than in the small intestine, which results in low blood SCFAs in humans, meaning that SCFAs may have no effect on metabolic health. SCFAs may be utilized as an energy source by stomach cells.

[0101] The data also show that for Oil Composition B, sufficient amounts of caproic and butyric acid residues are cleaved from triglycerides in the small intestine to result in increased blood concentrations of these fatty acids and therefore positive systemic effects on metabolic health without the need for gut bacteria.

[0102] Furthermore, oil composition B reached the large intestine in greater amounts than oil composition A, which had a positive effect on the microflora, gastrointestinal health and inflammation.

[0103] In addition, the bioavailability (ie, the ability to be absorbed through the gastrointestinal tract and therefore enter the systemic circulation) of the butyric acid residues (C4:0) and caproic acid residues (C6:0) in Oil Composition B is higher than in Oil Composition A. [Example]

[0104] Two oil compositions of the present invention were prepared: Oil Composition E and Oil Composition F.

[0105] The methods for producing oil compositions E and F include: A) a first starting oil composition comprising 71% by weight of butyric acid residues (C4:0) and 29% by weight of caproic acid residues (C6:0), and a second starting vegetable oil which is high oleic sunflower oil, comprising approximately 90% by weight of unsaturated C 16 -C 18 providing the second starting vegetable oil comprising fatty acids; B) One of the following: a) 8.5 wt. % of the first starting oil composition and 91.5 wt. % of the second starting oil composition to form a mixture; or b) 30 wt. % of the first starting oil composition and 70 wt. % of the second starting oil composition to form a mixture. mixing the C) performing chemical transesterification using sodium methoxide; D) carrying out decolorization using bleaching earth and citric acid; E) Deodorization is carried out at 150°C to obtain a first oil composition 1 (a) from the mixture obtained in step B) and a second oil composition 2 (b) from the mixture obtained in step B), and F) a) 59.5 wt. % of the first oil composition 1, 31.5 wt. % of the second oil composition 2, and 9 wt. % of a non-transesterified oil that is high oleic sunflower oil to form an oil composition E; or b) 72 wt. % of the second oil composition 2 and 28 wt. % of a non-interesterified oil, which is high oleic sunflower oil, to form oil composition F. mixing the Includes:

[0106] In the first starting oil composition, the butyric acid residues are derived from a microbial source and the caproic acid residues are derived from palm kernel oil.

[0107] The various oil compositions produced are summarized below: The fatty acid profile (i.e. composition) was determined by fatty acid methyl ester analysis (FAME) using gas chromatography according to ISO 16958.

[0108] Table 2 also includes the fatty acid profile of Oil Composition D, a control oil composition not according to the invention, used in the experiments discussed below in Example 3. Oil Composition D was a high oleic sunflower oil. [Table 2]

[0109] In composition E, 44.9% of the caproic and butyric acid residues present are from one C 16 -C 18 The fatty acid triglycerides contained 35.9% of the caproic and butyric acid residues present. 16 -C 18 Of the caproic and butyric acid residues present, 19.2% were present in triglycerides containing three fatty acids selected from butyric or caproic acid, respectively.

[0110] In composition F, 53.4% ​​of the caproic and butyric acid residues present are 1 C 16 -C 18 The fatty acid triglycerides contained 21.0% of the caproic and butyric acid residues present. 16 -C 18 Of the caproic and butyric acid residues present, 25.6% were present in triglycerides containing three fatty acids selected from butyric acid or caproic acid, respectively. [Example]

[0111] A clinical trial was conducted involving orally administering Oil Composition D, Oil Composition E, and Oil Composition F discussed in Example 2 to subjects.

[0112] The effects of oral administration of various oil compositions, particularly on bioaccessibility, absorption, and postprandial gastrointestinal health, were studied in 12 male participants. Participants were either overweight or obese, aged between 40 and 70 years, with normal fasting blood glucose (<7.1 mmol / L) and a body mass index (BMI) of 25-35 kg / m. 2 Their blood pressure was within the normal range, and their weight had been stable for at least the last 3 months prior to the study. Participants did not have any of the following conditions: fasting plasma glucose >7.1 mmol / L, gastrointestinal disease, diabetes mellitus, history of diabetes mellitus, history of major abdominal surgery, cardiovascular disease, cancer, liver or kidney failure, diseases with a life expectancy <5 years, alcohol or drug abuse, excessive smoking (>20 cigarettes per day), or exercise training (>3 hours per week). Furthermore, participants did not follow a low-calorie, vegan, or vegetarian diet in the 3 months prior to or during the study, and did not use laxatives, prebiotics, probiotics, or antibiotics. Participants also did not use any medications affecting glucose, lipid metabolism, or inflammation (e.g., beta-blockers, corticosteroids, and cholesterol-lowering drugs, among others). Participants were euglycemic and had adequate renal and hepatic function.

[0113] Participants were studied in a multi-day clinical trial (CID). On each clinical trial day, participants were administered a meal (milkshake). The meal was selected to provide sufficient energy intake for the 6-hour study.

[0114] On one of the clinical trial days, each participant was administered 10 g of a control dose (Composition D) in addition to a meal. On another clinical trial day, each participant was administered 10 g of Composition E (i.e., Dose 1) in addition to a milkshake. On another clinical trial day, each participant was administered 10 g of Composition F (i.e., Dose 2) in addition to a milkshake.

[0115] Composition E (Dose 1) was selected to provide a first dose of caproic and butyric acid, and Composition F (Dose 2) was selected to provide a higher dose of caproic and butyric acid.

[0116] Table 3 shows the amounts of butyric acid residues (C4:0) and caproic acid residues (C6:0) in liquid oil compositions D, E and F. [Table 3]

[0117] A washout period of at least 1 week (and a maximum of 4 weeks) was maintained between CIDs to prevent any potential carryover effects from previous clinical investigation days (CIDs). The evening before each CID, participants consumed a low-fiber standardized meal called "Aviko maaltijdpannetje malse kipfilet" (2.5 g fat, 11.5 g carbohydrates, and 4.5 g protein per 100 g of product). For the CID itself, participants participated after an overnight fast (≥10 h) and had a cannula inserted into the antecubital vein in their arm to allow for continuous venous blood sampling.

[0118] To assess gastrointestinal discomfort, participants completed the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. The GSRS asked participants to rate the presence of any of the following on a scale of 0 (not at all) to 5 (very much): nausea, abdominal pain, abdominal discomfort, bloating, belching / diarrhea, and flatulence. Participants were also able to elaborate on any additional comments regarding gastrointestinal discomfort, such as diarrhea or constipation, via a general question. The mean gastrointestinal discomfort score was 1, indicating that participants did not experience any discomfort after consuming the various oil compositions.

[0119] To measure the effects of butyrate / caproate-rich triglycerides on substrate metabolism, particularly plasma SCFA concentrations, under postprandial conditions, venous blood sampling was repeated at 30, 60, 120, 180, 240, 300, and 360 minutes after consumption of vegetable oil compositions D, E, and F. For SCFA analysis, blood samples were collected in pre-chilled 5 mL heparin tubes (Becton Dickinson, The Netherlands) because EDTA can interfere with chromatographic results. After collection, all tubes were centrifuged at 3000 rpm for 15 minutes at 4°C, after which plasma was immediately aliquoted, flash-frozen in liquid nitrogen, and stored in a -80°C freezer until analysis.

[0120] For SCFA analysis, a plasma volume of 150 μl was used for SCFA measurement. The internal standard (IS), 2-ethylbutyric acid, was added at a concentration of 36 μM. Derivatization was performed by adding 25 μl of a 160 mM 3-nitrophenylhydrazine (NPH) solution and 25 μl of a 200 mM 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride solution. The mixture was incubated at 50°C for 30 min. A standard curve was prepared in the same manner as for the plasma samples. The standard concentration ranges were 5–400 μM for acetic acid and 0.1–20 μM for the other SCFAs.

[0121] The SCFA-NPH derivatives were extracted by adding diethyl ether, mixing for 15 minutes, and centrifuging at 6000 g for 10 minutes. The upper diethyl ether layer was collected and dried under a nitrogen gas flow. Finally, the residue containing the SCFA-NPH derivatives was dissolved in 60 μl of MeOH:water 25:75 (v / v) and directly measured by liquid chromatography-mass spectrometry (LC-MS). This liquid chromatography was performed using a microflow high-performance liquid chromatography (HPLC) system (Dionex Ultimate 3000) at a flow rate of 200 μl / min. 20 μl of the SCFA extract was loaded onto a Hypersil gold C18 UHPLC column, 10 cm x 2.1 mm internal diameter, 1.9 μm particle size (Thermo Fisher Scientific) at 35°C. The mobile phase consisted of solvent A (MeOH:water:FA:AF 10:90:0.1:0.05 v / v) and solvent B (MeOH:water:FA:AF 99:1:0.1:0.05 v / v). The following gradient conditions were applied: 0–2 min isocratic at 25% solvent B; 2–11 min linear gradient from 25% to 98% solvent B; 11–12.5 min isocratic at 98% solvent B to wash out any remaining peaks eluting after the last peak of interest; 12.5–16 min isocratic at 25% solvent B to the initial gradient for column re-equilibration. The HPLC was connected online to a Q Exactive (Thermo Fisher Scientific) equipped with a heated electrospray ionization (HESI) probe (Thermo Fisher Scientific). The mass spectrometer was operated in negative ionization mode. Measurements were performed in targeted selected ion monitoring (tSIM) mode, with a resolution set to 70,000, a maximum injection time of 200 ms, and an isolation window of 4 m / z.The inclusion list was 194.06 m / z for acetate-NPH (C2), 208.07 m / z for propionate-NPH (C3), 222.09 m / z for butyrate-NPH (C4), 236.10 m / z for valerate-NPH (C5), and 250.12 m / z for caproate-NPH (C6). Quantitation by peak area integration and plotting of each calibration curve was performed using Thermo Scientific Xcalibur 4.4 software (Thermo Fisher Scientific).

[0122] Figure 1 shows that the blood absorption of butyric acid residues (C4:0) after consuming oil compositions E and F according to the present invention is higher than the blood absorption of butyric acid residues (C4:0) after consuming oil composition D. Figure 2 shows that compositions E and F significantly increase the blood absorption of caproic acid (C6:0) more than the control composition D.

[0123] It can be concluded from the data that gastrointestinal absorption of SCFAs in the small intestine (and therefore postprandial plasma concentrations) is higher for the compositions of the invention than for control composition D.

[0124] It is also interesting to note that despite having a lower SCFA content, oil composition E showed better absorption of SCFA into the blood than oil composition F. Without wishing to be bound by theory, the two C 16 -C 18 This may be due to the higher percentage of SCFAs present in the triglycerides containing fatty acids in Composition E than in Composition F. Therefore, the triglycerides contain one caproic acid residue and two C 16 -C 18 If the triglyceride contains a fatty acid residue, it is 16 -C 18 It is hypothesized that gastric lipase is more inhibited in the stomach from cleaving caproic acid from its glycerol backbone than if fatty acids alone were present. This finding is unexpected.

[0125] Survey results included blood metabolites (glucose, triglycerides, and free fatty acids (FFA)), hormones (insulin, active glucagon-like peptide-1 (GLP-1), and total GLP-1), as well as inflammatory markers (tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ)).

[0126] Plasma FFAs, triglycerides, and glucose were assessed in plasma samples using an automated spectrophotometer (ABX Pentra 400 Autoanalyzer, Horiba ABX, Montpellier, France) and an automated Cobas Fara spectrophotometer (Roche Diagnostics, Basel, Switzerland). Plasma insulin was assessed using a commercially available radioimmunoassay (RIA) kit (human insulin-specific RIA, Millipore Corporation, Billerica, MA, USA), and inflammatory marker concentrations were assessed using multiple enzyme-linked immunosorbent assays (Human ProInflammatory II 4-Plex Ultra-Sensitive Kit, Meso Scale Diagnostics, Rockville, MD, USA). Total GLP-1 immunoreactivity was assessed as previously described using antisera co-reactive with the intact GLP-1 molecule and its major (N-terminally truncated) metabolite.

[0127] FIG. 3 illustrates that the postprandial response of the hormone active glucagon-like peptide-1 (GLP-1), which can affect appetite and weight regulation, is similar after consuming Oil Composition D, Oil Composition E, and Oil Composition F.

[0128] As shown in Figure 4, the postprandial response of glucose is similar after consuming oil compositions D, E and F.

[0129] As shown in Figure 5, the postprandial insulin response is similar after consuming oil compositions D, E and F.

[0130] Figures 6 and 7 show that the postprandial response of inflammatory markers such as TNF-α and IFN-γ was lower after consuming oil compositions E and F than after consuming vegetable oil composition D. This is interesting because it shows that the oil compositions of the present invention reduce the levels of circulating biomarkers of inflammation in the plasma.

[0131] Thus, the oil composition of the present invention increased the absorption of SCFAs, specifically butyrate (C4:0) and caproate (C6:0) residues, in the participants' small intestines and blood when compared with the control oil composition D. Furthermore, the oil composition of the present invention was well tolerated because it did not interfere with their gastrointestinal health. Postprandial responses of inflammatory markers were also lower with the composition of the present invention than with the control composition. Furthermore, blood glucose levels were maintained at healthy levels below 7.1 mmol L. [Example]

[0132] Experiments were conducted to investigate the potential of caproic acid and butyric acid to reduce (low-grade) inflammation in adipose tissue.

[0133] Low-grade inflammation in adipose tissue is known to be mechanistically linked to metabolic diseases and organ-tissue complications that are thought to lead to obesity and weight gain in the organism. Low-grade inflammation in adipose tissue can be characterized by increased production of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNFα, and a phenotypic switch from an anti-inflammatory M2 state to a pro-inflammatory M1 state.

[0134] To determine the effect of butyrate and caproate on the production of the pro-inflammatory cytokine IL-6 under inflammatory conditions, we conducted an experiment in which we treated stem cell-derived adipocytes with butyrate and caproate, then added lipopolysaccharide (LPS) to induce inflammation, increasing the production of the pro-inflammatory biomarker IL-6.

[0135] Materials and Methods Pooled human multipotent adipose tissue-derived stem cells (hMADS) were differentiated into the adipogenic lineage to generate a human white adipocyte model. hMADS cells were cultured in subjects with a BMI of 20–40 kg / m². 2 The cells were derived from male human donors representing a wide range of phenotypes and glucometabolic status, and aged between 35 and 70 years. Cells were grown at 2,000 cells / cm in growth medium containing Dulbecco's modified Eagle's medium (DMEM), Ham's F-12 nutrient mixture (Gibco, Bleiswijk, The Netherlands), 10% fetal bovine serum (Bodinco BV, Alkmaar, The Netherlands), 50 U / ml penicillin (Gibco), and 50 μg / ml streptomycin (Gibco). 2 The seeds were sown at a density of 1000 and stored.

[0136] At 70–80% confluence, adipogenic differentiation was induced by adding 250 μmol / L IBMX (Sigma, St. Louis, Michigan, USA) and 5 μmol / L rosiglitazone (Enzo Life Sciences, Raamsdonksveer, The Netherlands). Experiments were performed between days 12 and 14 of differentiation.

[0137] Butyric acid and hexanoic acid (10 -4 ~10 -9 To examine the effect of various concentrations of butyrate or hexanoate (mol) on IL-6 release, hMADS adipocytes were incubated with various concentrations of butyrate or hexanoate. After 24 hours, 5 μg / mL LPS was added for an additional 24 hours. Cell supernatants were collected for IL-6 analysis.

[0138] IL-6 cytokine levels were assessed in culture supernatants using an electrochemiluminescence (ECL) immunoassay (MSD; Rockville, Maryland) according to the manufacturer's protocol.

[0139] Three independent identical experiments were performed and the average of these experiments is shown.

[0140] result The results are shown in Figure 8 (butyric acid) and Figure 9 (hexanoic acid). For both hexanoic acid and butyric acid, at all tested concentrations, the concentration of IL-6 was found to be lower than in cells treated with LPS but not subsequently with these fatty acids. Thus, the results show that both butyric acid and hexanoic acid reduce the concentration of the pro-inflammatory cytokine IL-6 in adipose tissue, suggesting that all tested fatty acids can reduce (low-grade) inflammation in adipocytes. This suggests that fatty acids have the activity to reduce obesity and the inflammatory processes that contribute to obesity development. [Example]

[0141] Another experiment was performed to determine the extent to which butyric acid, caproic acid, and combinations of these fatty acids affect the expression of the anti-inflammatory biomarker IL-10 in adipose tissue-derived stem cells.

[0142] In experiments, adipose tissue-derived stem cells were pretreated with butyrate, caproate, or a combination of these, and then lipopolysaccharide (LPS) was added to induce low-grade inflammation. LPS incubation reduced the expression of the anti-inflammatory biomarker IL-10.

[0143] Materials and Methods Pooled human multipotent adipose tissue-derived stem cells (hMADS) were differentiated into the adipogenic lineage to generate a human white adipocyte model. hMADS cells were cultured in subjects with a BMI of 20–40 kg / m². 2 The cells were derived from male human donors representing a wide range of phenotypes and glucose metabolic status, and aged between 35 and 70 years. Cells were grown at 2,000 cells / cm in growth medium containing Dulbecco's modified Eagle's medium (DMEM), Ham's F-12 nutrient mixture (Gibco, Bleiswijk, The Netherlands), 10% fetal bovine serum (Bodinco BV, Alkmaar, The Netherlands), 50 U / ml penicillin (Gibco), and 50 μg / ml streptomycin (Gibco). 2The seeds were sown at a density of 1000 and stored.

[0144] At 70-80% confluence, adipogenic differentiation was induced by adding 250 μmol / L IBMX (Sigma, St. Louis, MI, USA) and 5 μmol / L rosiglitazone (Enzo Life Sciences, Raamsdonksveer, The Netherlands). Experiments were performed between days 12 and 14 of differentiation.

[0145] Butyric acid (10 -4 M) and hexanoic acid (10 -5 To investigate the effect of M) on the expression of the anti-inflammatory cytokine IL-10, hMADS-derived adipocytes were incubated with butyrate, hexanoate, or their combination. After 24 hours, 5 μg / mL LPS was added for an additional 24 hours. Cells were harvested for IL-10 and IL-6 analysis.

[0146] To measure IL-10 mRNA expression, total RNA was extracted from hMADS-derived adipocytes using TRIzol reagent (Invitrogen) and SYBR-Green. Real-time PCR was performed using iCycler (Biolegio, Nijmegen, The Netherlands; primer sequence). Results were normalized for 18S ribosomal RNA (calculation of delta-delta Ct values).

[0147] Two independent and identical experiments were performed and the mean of the experiments is represented.

[0148] result The results of the experiment are shown in Figure 10. LPS was found to reduce the expression of the anti-inflammatory cytokine IL-10. All butyrate and hexanoate concentrations tested showed a smaller increase in IL-10 expression than samples treated with LPS but without short-chain fatty acids. This suggests that all of the short-chain fatty acids tested increased the expression of the anti-inflammatory cytokine IL-10, and that all of the fatty acids are associated with the prevention or reduction of low-grade inflammation in adipose tissue. This suggests that fatty acids have the activity of reducing or preventing obesity.

[0149] Surprisingly, a large and synergistic increase in IL-10 expression was observed in samples treated with both butyric acid and hexanoic acid. This increase in IL-10 expression was a two-fold increase over the expression levels of each fatty acid alone. These results suggest that the combination of butyric acid and caproic acid can be used to produce desirable and synergistic increases in anti-inflammatory biomarkers, suggesting that the combination of these fatty acids may have a synergistic effect in preventing or ameliorating inflammatory effects in obesity.

Claims

【Request Item 1】 1% to 20% by weight of caproic acid residues (C6:0), and at least 55% by weight of C １６ -C １８ Unsaturated fatty acid residues, and less than 40% by weight of C ８ -C ２４ An oil composition containing saturated fatty acid residues, wherein the percentage of fatty acid residues refers to fatty acids bonded as acyl groups to glycerides in the oil composition, and saturated and unsaturated C20 ４ -C ２４ The oil composition is based on the total weight of fatty acid residues, wherein at least 50% of the caproic acid residues present in the oil composition are present in a triglyceride comprising at least one caproic acid residue and at least one fatty acid residue containing 16 to 18 carbon atoms.

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