Application of medium-chain fatty acid mixed structure lipids in improving diet-induced glucose and lipid metabolism disorders

Abstract

The present application discloses an application of a medium-chain fatty acid mixed structure lipid in improving diet-induced glucose and lipid metabolism disorders, wherein the medium-chain fatty acid mixed structure lipid contains capric lauric acid triglyceride and capric lauric acid diglyceride; the mass percentage ratio of capric acid to lauric acid in the medium-chain fatty acid mixed structure lipid is 1:1 to 1:4. The present application finds that adding medium-chain fatty acid mixed glycerides rich in lauric acid to high-energy feed can improve diet-induced glucose and lipid metabolism disorders, including but not limited to lowering serum glucose levels, improving sugar homeostasis, lowering serum low-density lipoprotein cholesterol levels, and improving glucose and lipid metabolism-related gene expression.

Description

Technical Field

[0001] The present application relates to the technical field of functional structural lipids, and in particular to the application of a medium-chain fatty acid mixed structural lipid rich in lauric acid in improving diet-induced glucose and lipid metabolism disorders. Background Art

[0002] With the improvement of living standards, people's dietary structure has undergone major changes, among which the proportion of high-energy diet has increased significantly, resulting in excessive energy intake, which in turn promotes fat cell hypertrophy and ectopic fat deposition, leading to lipid metabolism disorders. Structural fats refer to new types of fats that structurally modify fats by changing the fatty acid composition and arrangement on the glycerol skeleton to enhance their physicochemical properties and nutritional value. Compared with natural fats, structural fats can improve the physicochemical properties of fats, which is more conducive to the development and utilization of fats. The content of functional fatty acids can be increased by synthesizing structural fats, so that structural fats can play a better physiological function. Studies have shown that structural fats have a positive effect on reducing fat accumulation and improving lipid metabolism.

[0003] Caprylic acid, capric acid and glycerol can react to obtain caprylic decanoate (ODO), which is widely used in food. However, studies have shown that caprylic acid may have adverse effects on glucose and lipid metabolism, further aggravating the increase in blood sugar and cholesterol metabolism induced by a high-fat diet. It may also aggravate obesity-induced changes in the bone marrow microenvironment and promote bone metastasis of cancer. Summary of the invention

[0004] The present application finds that medium-chain fatty acid mixed glycerides rich in lauric acid have the effect of improving the glucose and lipid metabolism disorders induced by diet, including but not limited to lowering serum glucose levels, improving glucose homeostasis, lowering serum low-density lipoprotein cholesterol levels and improving the expression of genes related to glucose and lipid metabolism.

[0005] Based on the discovery of new functions of medium-chain fatty acid mixed glycerides rich in lauric acid in this application:

[0006] The first purpose of the present application is to provide a medium-chain fatty acid mixed structure fat for use in the preparation of health products or foods for improving diet-induced glucose and lipid metabolism disorders, wherein the medium-chain fatty acid mixed structure fat contains capric lauric acid triglyceride and capric lauric acid diglyceride.

[0007] The second purpose of the present application is to provide a medium-chain fatty acid mixed structure fat for use in the preparation of feed for improving glucose and lipid metabolism disorders induced by a high-energy diet, wherein the medium-chain fatty acid mixed structure fat contains capric lauric acid triglyceride and capric lauric acid diglyceride.

[0008] For the above two applications:

[0009] Optionally, the mass percentage ratio of capric acid to lauric acid in the medium-chain fatty acid mixed structure fat is 1:1 to 1:4. Further, the mass percentage ratio of capric acid to lauric acid in the medium-chain fatty acid mixed structure fat is 1:2 to 1:3.

[0010] Optionally, the capric lauric triglyceride is capric dilauric triglyceride and dicapric monolauric triglyceride; the capric lauric diglyceride is capric monolauric diglyceride.

[0011] Optionally, the monocapric dilauric triglyceride is at least one of 1-capric acid-2,3-dilauric acid glyceride and 1,3-dilauric acid-2-capric acid glyceride;

[0012] The dicaprylic acid monolauric acid triglyceride is at least one of 1,2-dicaprylic acid-3-lauric acid glyceride and 1,3-dicaprylic acid-2-lauric acid glyceride;

[0013] The monocapric monolauric diglyceride is at least one of 1-capric-3-lauric diglyceride, 1-capric-2-lauric diglyceride and 2-capric-1-lauric diglyceride.

[0014] Optionally, the medium-chain fatty acid mixed structure lipid contains, by mass percentage:

[0015] Capric dilauric triglyceride not less than 30%;

[0016] Dicaprylic acid monolauric acid triglyceride 15~30%;

[0017] Monolauric acid diglyceride 20~25%.

[0018] Optionally, the improvement of the diet-induced glucose and lipid metabolism disorder includes at least one of lowering serum glucose levels, improving glucose homeostasis, lowering serum low-density lipoprotein cholesterol levels, and improving the expression of genes related to glucose and lipid metabolism.

[0019] Regarding its application in the preparation of health products or foods:

[0020] Optionally, the medium-chain fatty acid mixed structure fat can be directly added to food or prepared into soft capsules as a dietary supplement or health product, and the recommended daily intake is 0.25 g to 2.30 g; more preferably, the recommended daily intake of the medium-chain fatty acid mixed structure fat is 0.6 g to 1.50 g; optimally, the recommended daily intake of the medium-chain fatty acid mixed structure fat is 0.8g to 1.2 g.

[0021] For application as feed additive:

[0022] Optionally, the medium-chain fatty acid mixed structured lipid is added to high-energy feed at 100-3000 mg / kg.

[0023] Furthermore, the medium-chain fatty acid mixed structural fat is added to the high-energy feed at 300-2500 mg / kg; more preferably, the medium-chain fatty acid mixed structural fat is added to the high-energy feed at 800- ～ 1500 mg / kg is added to high-energy feed; most preferably, the medium-chain fatty acid mixed structure lipid is added to high-energy feed at 1000-1200 mg / kg.

[0024] Optionally, the high-energy feed generally refers to high-fat feed, high-sugar feed or high-fat and high-sugar feed, such as feed with a fat energy supply ratio exceeding 35%, a fat energy supply ratio in the range of 35-70%, or a feed containing 60% fructose or sucrose; further, it can be a high-fat feed with a fat energy supply ratio of 45%.

[0025] The present application also provides a medium-chain fatty acid mixed structure fat, wherein the medium-chain fatty acid mixed structure fat contains capric lauric acid triglyceride and capric lauric acid diglyceride; the mass percentage content ratio of capric acid to lauric acid in the medium-chain fatty acid mixed structure fat is 1:1 to 1:4. Furthermore, the mass percentage content ratio of capric acid to lauric acid in the medium-chain fatty acid mixed structure fat is 1:2 to 1:3.

[0026] The present application also provides a method for preparing the medium-chain fatty acid mixed structure lipid, comprising:

[0027] Capric acid, lauric acid and glycerol are mixed at 45-75°C, and after they are fully liquefied and mixed, immobilized lipase or chemical catalyst is added, vacuum is evacuated or molecular sieves are added, and the mixture is kept warm for 4-12 hours. After the solids are removed by filtration, unreacted fatty acids, glycerol and monoglycerides are removed by molecular distillation or chemical separation to obtain the medium-chain fatty acid mixed structure lipid.

[0028] Compared with the prior art, this application has the following beneficial effects:

[0029] The present study found that lauric acid-rich medium-chain fatty acid mixed structure lipids, compared with capric acid-rich medium-chain fatty acid mixed structure lipids and other similar products, caprylic / capric glyceride, can significantly improve the glucose metabolism disorders induced by a high-energy diet, including but not limited to lowering serum glucose levels, improving glucose homeostasis, lowering serum low-density lipoprotein cholesterol levels, and improving the expression of genes related to glucose and lipid metabolism. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is a graph showing the effects of different doses of capric lauric acid mixed structural lipids and caprylic decanoic acid glyceride on glucose and lipid metabolism;

[0031] Figure 2 This is the result diagram of the effect of capric acid and lauric acid mixed structure lipid on glucose metabolism;

[0032] Figure 3 This is the result diagram of the effect of capric acid and lauric acid mixed structure lipid on serum lipid metabolism related indicators;

[0033] Figure 4 This is a graph showing the effect of capric acid and lauric acid mixed structured lipids on the expression of genes related to liver glucose and lipid metabolism. DETAILED DESCRIPTION

[0034] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0035] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

[0036] The present application provides a capric lauric acid mixed structural fat rich in lauric acid, whose components include capric dilaurin, dicapric monolaurin and capric monolaurin diglycerol, and the mass percentage ratio of capric acid to lauric acid in the capric lauric acid mixed structural fat is 1:1~1:4, and further preferably 1:2~1:4.

[0037] Among them, the monocapric dilaurin is at least one of 1-capric-2,3-dilaurin and 2-capric-1,3-dilaurin; the dicapric monolaurin is at least one of 1,2-capric-3-laurin and 1,3-capric-2-laurin; and the monocapric monolaurin diglyceride includes at least one of 1-capric-3-laurin, 1-capric-2-laurin and 2-capric-1-laurin.

[0038] A method for synthesizing the above-mentioned mixed structure lipid comprises: esterification reaction of capric acid, lauric acid and glycerol to synthesize capric acid lauric acid mixed structure lipid. Esterification reaction refers to the process of generating ester compounds by the reaction of fatty acids and alcohols under the catalysis of acid, base or enzyme.

[0039] When the esterification reaction occurs, the molar ratio of capric acid, lauric acid and glycerol is 1: (1-8): 1. Preferably, the molar ratio is 1: (2-4): 1, and the mixed structure lipid synthesized under this condition is rich in lauric acid.

[0040] When the esterification reaction occurs, 4-12% of the substrate weight of immobilized lipase or 0.2-0.8% of the substrate weight of chemical catalyst is added. The immobilized lipase used is any one of immobilized Aspergillus oryzae lipase, Rhizopus oryzae lipase and Rhizopus miehei lipase, and the chemical catalyst is a strong acid or a strong base.

[0041] The steps of the esterification reaction are as follows: the reactants are mixed at 45-75°C, and after they are fully liquefied and mixed, immobilized lipase is added, vacuum is drawn or molecular sieves are added, and the reaction is kept warm for 4-10 hours. After filtering to remove the solids, fatty acids, glycerol and monoglycerides are removed by molecular distillation or chemical catalysis to obtain a capric acid lauric acid mixed structure lipid.

[0042] A use of the above-mentioned mixed structural lipid in improving the glucose and lipid metabolism disorder induced by a high-energy diet. In some examples, at least one of the following needs to be satisfied: at least one of the functions of lowering serum glucose levels, improving glucose homeostasis, lowering serum low-density lipoprotein cholesterol levels, and improving the expression of genes related to glucose and lipid metabolism is achieved.

[0043] The above method was used to synthesize the mixed structured lipids of capric laurate (LDL) rich in lauric acid and capric laurate (DLD) rich in capric acid. The physical mixed oil (MLD) was obtained by directly mixing tricaprin and trilaurin according to the fatty acid molar ratio of LDL. Octyldecanoic acid glyceride (ODO) is a commercially available product. Animal experiments were performed to evaluate the efficacy of mixed structured lipids in improving diet-induced glucose and lipid metabolism disorders. C57BL / 6J mice were randomly divided into 10 groups in each group, with free diet and water, and samples were taken after 16 weeks. The control group was fed with ordinary feed (fat energy supply ratio was 10%), the high-energy group was fed with high-fat feed (fat energy supply ratio was 45%), experimental group 1 was fed with high-fat feed supplemented with 300-2400 mg / kg LDL, experimental group 2 was fed with high-fat feed supplemented with 300-2400 mg / kg DLD, experimental group 3 was fed with high-fat feed supplemented with 300-2400 mg / kg ODO, and experimental group 4 was fed with high-fat feed supplemented with 300-2400 mg / kg MLD.

[0044] The following is described with specific examples:

[0045] Example 1: Synthesis of capric acid and lauric acid mixed structure lipid

[0046] Capric acid, lauric acid and glycerol were mixed in a molar ratio of 1:2:1 and placed in a 65 ℃ constant temperature water bath shaker. After complete melting and mixing, 10% immobilized lipase and an appropriate amount of molecular sieves were added, and the mixture was covered with a flip stopper and reacted at 200 rpm for 6 hours. The lipase and molecular sieves were filtered out. The product was dissolved in n-hexane, phenolphthalein was used as an indicator, and KOH methanol solution was titrated to pink. Excess fatty acids were removed, and n-hexane was removed by rotary evaporation to obtain a capric acid-lauric acid mixed structure lipid LDL rich in lauric acid. The ratio of capric acid and lauric acid was changed (i.e., capric acid, lauric acid and glycerol were mixed in a molar ratio of 2:1:1), and a capric acid-lauric acid mixed structure lipid DLD rich in capric acid was synthesized according to the above method. Appropriate amounts of the above mixed structure lipids were weighed respectively, and GC-MS (gas chromatography-mass spectrometry) was used for component identification. The composition is shown in Table 1 (LDL) and Table 2 (DLD).

[0047] Table 1 Composition of lauric acid-capric laurate mixed structured lipids (LDL)

[0048] (Capric acid: lauric acid = 1:2.3)

[0049]

[0050] Table 2 Composition of capric acid-lauric acid mixed structured lipid (DLD) rich in capric acid

[0051] (Capric acid: lauric acid = 1.7:1)

[0052]

[0053] Example 2: Capric and lauric acid mixed structured lipid improves high-fat diet-induced glucose and lipid metabolism disorders

[0054] C57BL / 6J mice were randomly divided into groups, 10 in each group, with free access to food and water. The NCD group was fed with a normal diet (10% fat energy supply ratio), the HFD group was fed with a high-fat diet (45% fat energy supply ratio), and the experimental groups were added with LDL at 300 and 1200 mg / kg (Table 1), DLD at 1200 mg / kg (Table 2) and MLD, and ODO at 800 and 1600 mg / kg in the high-fat diet, respectively. After 14 weeks of feeding, the mice were fasted overnight and glucose tolerance was measured. Blood was collected from the tail vein to measure fasting blood glucose, which was recorded as blood glucose at 0 min. Glucose solution (glucose amount was 2 g / kg body weight) was injected intraperitoneally, and blood glucose values ​​were measured from the tail vein 30, 60, 90, and 120 min later. The blood glucose curve was drawn and the area under the curve was calculated. After 16 weeks, the mice were fasted overnight, and fresh blood was collected by orbital bleeding. After standing for 30 min, the serum was centrifuged and stored at -80 ℃. Commercially available kits were used to measure the levels of serum glucose and lipid metabolism-related indicators.

[0055] Results of serum glucose and lipid metabolism-related indices of mice gavaged with different doses of LDL and ODO ( Figure 1 ) showed that 1200mg / kg LDL improved serum glucose (Glu) ( Figure 1 A), serum low-density lipoprotein cholesterol (LDL-C) ( Figure 1 D) and high-density lipoprotein cholesterol / low-density lipoprotein cholesterol ratio (HDL-C / LDL-C) ( Figure 1 The effect of 1600 mg / kg ODO in reducing serum glucose Glu was significantly stronger than that of 800 mg / kg ODO, and the effect of 1600 mg / kg ODO in reducing serum LDL-C was significantly stronger than that of 800 mg / kg ODO ( p = 0.0846). Serum total triglyceride (TG) in each group ( Figure 1 B) and serum total cholesterol (T-CHO) ( Figure 1 There was no significant difference in the levels in C), and the serum TG levels of 300 mg / kg LDL and 800 mg / kg ODO were slightly higher than those of 1200 mg / kg LDL and 1600 mg / kg ODO, respectively.

[0056] This comparison shows that:

[0057] (1) The effect of 1200 mg / kg LDL on improving glucose and lipid metabolism is better than that of 300 mg / kg LDL, and the effect of 1600 mg / kg ODO on improving glucose and lipid metabolism is better than that of 800 mg / kg ODO. Within a certain range, the effects of LDL and ODO on improving glucose and lipid metabolism increase with the increase of their added amount.

[0058] (4) The effect of 300 mg / kg LDL on improving lipid metabolism is close to that of 1600 mg / kg ODO.

[0059] (3) The effect of 1200 mg / kg LDL on improving glucose and lipid metabolism was significantly better than that of 1600 mg / kg ODO.

[0060] This indicates that capric laurate structured lipid can achieve better effects in improving diet-induced glucose and lipid metabolism disorders than caprylic laurate at a lower dose.

[0061] The results of the glucose tolerance test showed that ( Figure 2In A and B, there was no significant difference in the initial blood glucose of each group. At 30, 60, and 90 minutes after intraperitoneal injection of glucose, the blood glucose of each group fed with a high-fat diet was higher than that of the NCD group. After 120 minutes, the blood glucose of each group returned to a similar level. Statistical analysis of the area under the curve (AUC) showed that the area under the curve (AUC) of each group fed with a high-fat diet was significantly higher than that of the NCD group. DLD, ODO, and MLD had no significant effect on this. The area under the curve (AUC) of the LDL group was significantly lower than that of the HFD group, indicating that LDL can improve the destruction of glucose homeostasis induced by a high-fat diet. The results of serum glucose levels are shown in Figure 2 As shown in C. LDL can significantly reduce the increase in blood sugar induced by a high-fat diet, ODO ( p = 0.0521) and MLD ( p = 0.0744) showed a trend towards lowering blood sugar but it was not significant.

[0062] Effects of capric and lauric acid mixed structure lipids on serum lipid metabolism related indicators Figure 3 The serum total triglyceride (TG) of each group ( Figure 3 There was no significant difference in serum total cholesterol (T-CHO) levels, but the structured lipid DLD rich in capric acid further increased serum TG levels. Figure 3 B) and serum low-density lipoprotein cholesterol (LDL-C) ( Figure 3 C) levels, LDL, DLD and MDL had no significant effect on serum T-CHO levels, while ODO had a tendency to further increase serum T-CHO ( p = 0.099). MLD can reduce LDL-C to a certain extent ( p = 0.068) but not significantly, while LDL significantly reduced the level of serum LDL-C. From the high-density lipoprotein cholesterol / low-density lipoprotein cholesterol ratio (HDL-C / LDL-C) ( Figure 3 From the results of D), DLD and ODO had no significant improvement effect, while MLD and LDL could increase serum HDL-C / LDL-C, and the effect of LDL was more significant. The above results show that LDL has a good effect in regulating serum lipid metabolism.

[0063] Effects of capric and lauric acid mixed lipids on the expression of genes related to liver glucose and lipid metabolism Figure 4 High-fat diet increases the liver's gluconeogenesis-related G6pc (Glucose-6-phosphatase catalytic subunit gene) Figure 4 B) and Pepck (phosphoenolpyruvate carboxykinase gene) Figure 4 A) Expression of β-catenin in the liver of each experimental group G6pc and Pepck The expression of LDL, ODO and MLD was significantly lower than that of the HFD group, and the effect of LDL was the most significant. LDL significantly improved the liver glycolysis-related changes induced by high-fat diet. G (Hexokinase gene) Figure 4 C) expression was decreased, DLD and MLD had no significant effect on it, while ODO may further reduce liver G Express( p = 0.099). Pparg (peroxisome proliferator-activated receptor gamma gene) Figure 4 D) and Srebp1 (Sterol regulatory element binding protein 1 gene) Figure 4 Middle E) Related to lipid synthesis, LDL significantly downregulated the liver of mice fed a high-fat diet Pparg and Srebp1 DLD only reduced the expression of Pparg Expression of ODO and MLD in liver Pparg and Srebp1 There was no significant effect on the expression of .

[0064] In summary, compared with MLD, LDL significantly reduced serum Glu levels, improved glucose homeostasis and the expression of genes related to liver lipid metabolism, and had a more significant improvement effect on cholesterol metabolism and the expression of genes related to liver glucose metabolism, indicating that structural lipids are better than triglyceride physical mixed oils in improving glucose and lipid metabolism. Compared with DLD, LDL significantly reduced serum Glu levels, improved glucose homeostasis and cholesterol metabolism, and had a more significant improvement effect on the expression of genes related to liver glucose and lipid metabolism, indicating that lauric acid-capric lauric acid structural lipids rich in lauric acid are better than capric acid-capric lauric acid structural lipids rich in capric acid in improving glucose and lipid metabolism.

[0065] Compared with 1600 mg / kg of ODO, the added amount of LDL was lower (1200 mg / kg), and it was able to significantly reduce serum Glu levels, improve glucose homeostasis, cholesterol metabolism and liver lipid metabolism-related gene expression, and the effect of improving liver glucose metabolism-related gene expression was more significant, indicating that capric lauric acid structured lipid can achieve a better effect than caprylic lauric acid glyceride in improving diet-induced glucose and lipid metabolism disorders at a lower dose.

[0066] The above results show that the lauric acid-capric lauric acid mixed structured lipids can improve glucose homeostasis, regulate cholesterol metabolism, reduce liver lipid synthesis, and improve the glucose and lipid metabolism disorders induced by a high-fat diet. It is expected to be used in foods or health products that improve glucose and lipid metabolism disorders.

[0067] The above-mentioned embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application shall be subject to the attached claims.

Claims

1. A medium-chain fatty acid mixed structure lipid, characterized in that: The medium-chain fatty acid mixed structure fat contains capric lauric acid triglyceride and capric lauric acid diglyceride; the mass percentage content ratio of capric acid to lauric acid in the medium-chain fatty acid mixed structure fat is 1:1 to 1:4; The capric lauric triglyceride is capric dilauric triglyceride and dicapric monolauric triglyceride; the capric lauric diglyceride is capric monolauric diglyceride; In terms of mass percentage, the medium-chain fatty acid mixed structure lipid contains: Capric dilauric triglyceride not less than 30%; Dicaprylic acid monolauric acid triglyceride 15~30%; Monolauric acid diglyceride 20-25%; The preparation of the medium-chain fatty acid mixed structure lipid comprises: Capric acid, lauric acid and glycerol are mixed at 45-75°C, and after they are fully liquefied and mixed, immobilized lipase or chemical catalyst is added, vacuum is evacuated or molecular sieves are added, and the reaction is kept warm for 4-12 hours. After filtering to remove solids, unreacted fatty acids, glycerol and monoglycerides are removed by molecular distillation or chemical methods to obtain the medium-chain fatty acid mixed structure lipid.

2. The medium-chain fatty acid mixed structure lipid according to claim 1, characterized in that: The monocapric dilauric triglyceride is at least one of 1-capric acid-2,3-dilauric acid glyceryl and 1,3-dilauric acid-2-capric acid glyceryl; The dicaprylic acid monolauric acid triglyceride is at least one of 1,2-dicaprylic acid-3-lauric acid glyceride and 1,3-dicaprylic acid-2-lauric acid glyceride; The monocapric monolauric diglyceride is at least one of 1-capric-3-lauric diglyceride, 1-capric-2-lauric diglyceride and 2-capric-1-lauric diglyceride.

3. Use of the medium-chain fatty acid mixed structure lipid as claimed in claim 1 or 2 in the preparation of feed for improving diet-induced glucose and lipid metabolism disorders.

4. The use according to claim 3, characterized in that: The improvement of diet-induced glucose and lipid metabolism disorders includes at least one of lowering serum glucose levels, improving glucose homeostasis, lowering serum low-density lipoprotein cholesterol levels, and improving the expression of genes related to glucose and lipid metabolism.

5. The application according to claim 3, characterized in that: The medium-chain fatty acid mixed structural lipid is added into high-energy feed at 100-3000 mg / kg.

6. Use of the medium-chain fatty acid mixed structure lipid as claimed in claim 1 or 2 in the preparation of health products or foods.

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