Composition for improving lipid metabolism

Abstract

To provide a material that can inhibit dyslipidemia due to increased free fatty acids observed in obesity and diabetes.SOLUTION: A composition for improving lipid metabolism contains a specific material that can inhibit dyslipidemia due to fatty acid treatment.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present disclosure relates to a composition for improving lipid metabolism, etc. [Background technology]

[0002] It is known that insulin resistance occurs in diabetic patients. It is also believed that there is a relationship between diabetes and periodontal disease, and it has been reported that insulin resistance occurs in the gingiva of diabetic model animals. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] J Dent Res 2014: 93; 596-601. [Non-Patent Document 2] PLOS ONE 2017;12:e0189601. Summary of the Invention [Problem to be solved by the invention]

[0004] It is known that excessive administration of fatty acids (especially palmitic acid) can cause insulin resistance, but it has not been confirmed whether it also causes insulin resistance in gingival cells.

[0005] The present inventors found that insulin enhances Akt phosphorylation in periodontal ligament cells in a concentration-dependent manner, and that application of palmitic acid to periodontal ligament cells suppresses insulin-induced enhancement of Akt phosphorylation. Inhibition of Akt phosphorylation is widely known as one of the indicators of insulin resistance. This shows that fatty acids can also cause insulin resistance in gingival cells.

[0006] Furthermore, the inventors conducted similar studies on high concentrations of sugar (glucose) and LPS (Lipopolysaccharide), which are components other than fatty acids that are thought to have the potential to cause insulin resistance. However, treatment with high concentrations of sugar or LPS did not inhibit Akt phosphorylation, and therefore it was believed that these components do not cause insulin resistance.

[0007] Based on these findings, it can be assumed that the increase in free fatty acids (especially palmitic acid) caused by obesity and diabetes (especially type 2 diabetes) induces inflammation and monocyte adhesion in various cells, causing sustained bone resorption. In particular, regarding the relationship between diabetes and periodontal disease, it can be assumed that free fatty acids (especially palmitic acid) induce inflammation and monocyte adhesion in periodontal ligament cells, aggravating periodontitis accompanied by sustained bone resorption, which may ultimately lead to tooth loss.

[0008] We further examined whether free fatty acids (especially palmitic acid) could increase the expression of inflammatory cytokines, chemokines, and adhesion factors, as well as the expression of receptors located upstream of the inflammatory cytokine, chemokine, and adhesion factor expression cascade (Toll-like receptor 4 (TLR4) and CD36), and found that the expression of all of these genes was enhanced. TLR4 is a receptor protein that recognizes LPS, etc. CD36 is a major membrane protein involved in the uptake of fatty acids, and is thought to be involved in disorders of fatty acid and lipid metabolism that occur with the onset of pathophysiological conditions such as insulin resistance and diabetic cardiomyopathy caused by a high-fat diet.

[0009] From these findings, it was thought that by using the above-mentioned gene expression as an indicator, it would be possible to search for components that suppress lipid metabolism disorders caused by an increase in free fatty acids that occurs in obesity and diabetes. Therefore, further studies were carried out with the aim of searching for such components. [Means for solving the problem]

[0010] The present inventors have found various components capable of suppressing lipid metabolism disorders caused by fatty acid treatment (treatment in which a large amount of fatty acid is applied to cells), and have further improved them.

[0011] The present disclosure includes, for example, the subject matter described in the following sections: Section 1. Contains at least one selected from the group consisting of components listed in the table below: Composition for improving lipid metabolism.

[0012] [Table 1]

[0013] TIFF2024095194000002.tif231170

[0014] TIFF2024095194000003.tif231170

[0015] TIFF2024095194000004.tif111170

[0016] Section 2. Contains at least one selected from the group consisting of components listed in the table below: Composition for improving lipid metabolism.

[0017] [Table 2]

[0018] Section 3. Item 3. The composition according to item 1 or 2, for obese or diabetic patients. Section 4. The composition according to any one of Items 1 to 3, which is an oral composition. Section 5. Item 5. The composition according to any one of Items 1 to 4, which is for preventing arteriosclerosis. Effect of the Invention

[0019] It can suppress metabolic disorders caused by fatty acid treatment. [Brief description of the drawings]

[0020] [Figure 1A] The results show how the expression levels of inflammatory cytokines, chemokines, and adhesion molecules in human periodontal ligament fibroblasts (HPDLF) changed after treatment with palmitic acid and culturing for 6 or 24 hours. Palmitic acid was administered by conjugating it to bovine serum albumin (BSA). As a control, the cells were treated with the same amount of BSA that was not conjugated with palmitic acid. The results are values ​​obtained by correcting the expression levels of each gene with the expression level of ribosomal protein S18 (RPS18). [Figure 1B] The results show how the expression level of receptor genes changes after treating human periodontal ligament fibroblasts (HPDLF) with palmitic acid and culturing for 6 or 24 hours. Palmitic acid was administered by conjugating it to bovine serum albumin (BSA). As a control, the cells were treated with the same amount of BSA that was not conjugated with palmitic acid. The results are values ​​obtained by correcting the expression level of each gene by the expression level of ribosomal protein S18 (RPS18). [Diagram 2] This is an outline of an experiment to examine how the gene expression levels of inflammatory cytokines, chemokines, adhesion factors, and receptors change when human periodontal ligament fibroblasts (HPDLF) are first treated with a test substance (sample) and then treated with palmitic acid. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021] Each embodiment included in the present disclosure will be described in more detail below. The present disclosure preferably includes, but is not limited to, a lipid metabolism improving composition, and the like, and the present disclosure includes all that is disclosed in the present specification and that can be recognized by a person skilled in the art.

[0022] The lipid metabolism improving composition included in the present disclosure contains the specific components listed in the following table, either singly or in combination of two or more. The lipid metabolism improving composition included in the present disclosure may be referred to as the composition of the present disclosure. In addition, the components with these characteristics may be referred to as the components of the present disclosure.

[0023] [Table 3]

[0024] TIFF2024095194000007.tif231170

[0025] TIFF2024095194000008.tif231170

[0026] TIFF2024095194000009.tif111170

[0027] Among these components, the components listed in the following table are more preferred.

[0028] [Table 4]

[0029] The content of the components of the present disclosure in the composition of the present disclosure is not particularly limited as long as the effects are not impaired, and may be, for example, about 0.01 to 99.99% by mass.

[0030] The intake form of the composition of the present disclosure is not particularly limited, but is preferably oral intake. That is, the composition of the present disclosure is preferably an oral composition. By orally ingesting the composition of the present disclosure, the effect of suppressing lipid metabolism abnormalities in cells (particularly cells in the oral cavity) can be preferably achieved. The composition of the present disclosure is preferably, for example, an oral pharmaceutical composition or a food composition (including a beverage composition and a food additive composition).

[0031] The composition of the present disclosure includes the above-mentioned components and may further include other components. The other components may be appropriately selected depending on the field in which the composition is used. For example, a medicamentically or food hygienically acceptable carrier may be used.

[0032] When used as a pharmaceutical composition, other components include pharma- ceutically acceptable bases, carriers, and / or additives (e.g., solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, binders, disintegrants, lubricants, etc.), etc. The form of the pharmaceutical composition is not particularly limited, and examples thereof include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, creams, and poultices.

[0033] When used as a food composition, other ingredients include bases, carriers, additives that are acceptable from the viewpoint of food hygiene, and other ingredients and materials that can be used as foods. The form of the food composition is not particularly limited, and examples thereof include processed foods, health foods (nutritional supplements, nutritional functional foods, foods for the sick, foods for specified health uses, functional products, etc.), supplements, foods for the sick (hospital food, sick food, nursing food, etc.). These can be prepared by conventional methods. In particular, when preparing a food composition as a health food (nutritional supplements, nutritional functional foods, foods for the sick, foods for specified health uses, functional products, etc.) or supplements, it is preferable to prepare it in the form of, for example, granules, capsules, tablets (including chewable agents, etc.), beverages (drink powders, drinks, smoothies, etc.) so that it is easy to take continuously, and among them, the forms of capsules, tablets, tablets, drink powders, drinks, jellies, and gummies are preferable from the viewpoint of ease of intake, but are not particularly limited thereto. When the food composition is used as a food additive composition, the form of the composition may be, for example, liquid, powder, flake, granule, or paste.

[0034] From the viewpoint of favorable effects, the subject of taking the composition of the present disclosure is preferably a subject with lipid metabolism disorder, more preferably a subject with an increase in free fatty acid. Particularly preferred is a subject with an increase in inflammatory cytokines, chemokines, and adhesion factors due to an increase in free fatty acid, and examples of such inflammatory cytokines, chemokines, and adhesion factors include IL-6, CXCL1, ICAM-1, IL-8, etc.

[0035] Furthermore, the timing of ingesting the composition of the present disclosure is not particularly limited, and it may be used, for example, to be ingested before or after ingesting a meal.

[0036] In atherosclerosis, oxidized LDL accumulates in the vascular intima and is taken up by macrophages to form foam particles, which leads to the formation of plaque. It is well known that chronic inflammatory reactions are deeply involved in this process. Specifically, IL-6 is one of the representative inflammatory cytokines, and its expression is increased in arteriosclerotic tissues. In addition, chemokines such as CXCL1 and IL-8, and adhesion factors such as ICAM-1 are also increased in arteriosclerotic tissues, and promote plaque formation by mediating the attraction and adhesion of monocytes to the vascular endothelium of arteriosclerotic tissues. Therefore, the composition of the present disclosure is considered to be useful, for example, for the prevention and / or treatment of arteriosclerosis.

[0037] In addition, in this specification, the term "comprising" includes "consisting essentially of" and "consisting of." In addition, the present disclosure includes any combination of the constituent elements described in this specification.

[0038] In addition, the various characteristics (properties, structures, functions, etc.) described in each embodiment of the present disclosure above may be combined in any way to specify the subject matter included in the present disclosure. In other words, the present disclosure includes all subject matter consisting of all combinations of each combinable characteristic described in this specification. EXAMPLES

[0039] Hereinafter, the embodiments of the present disclosure will be described more specifically with reference to examples, but the embodiments of the present disclosure are not limited to the following examples.

[0040] Examination of periodontal ligament cells treated with palmitic acid Human periodontal ligament fibroblasts (HPDLF) were treated with palmitate to examine how the expression levels of various inflammatory cytokines, chemokines, adhesion molecules, and receptor genes changed (in Figure 2, the examination was performed under conditions without the addition of each test substance). The results are shown in Figures 1A and 1B. (The expression level of each gene was corrected by the expression level of ribosomal protein S18 (RPS18), and the relative value was calculated when the expression level after treatment with BSA was set to 1.) Furthermore, we investigated how the expression levels of various inflammatory cytokines, chemokines, adhesion molecules, and receptor genes changed when human periodontal ligament fibroblasts were treated with each test substance (sample) in advance and then treated with palmitic acid (Figure 2). More specifically, we conducted the study as follows. Note that the detailed explanation below is for the study described in Figure 2 (with test substance added), but the study described under conditions without test substance added, the results of which are shown in Figures 1A and 1B, was also conducted under the same conditions except for the test substance addition step.

[0041] [Examination of the expression of various inflammatory cytokines, chemokines, adhesion factor genes, and their receptor genes] Human periodontal ligament fibroblasts (HPDLF) were added at a concentration of 0.45 × 10 5The cells were seeded in a 12-well plate at a density of cells / 1mL / well and cultured for 72 hours. The cells were pretreated with each test substance (sample) (5μg / mL) for 24 hours, and then treated with 100μM palmitic acid (Sigma Aldrich) conjugated to BSA (Bovine serum albumin; Sigma Aldrich) for 24 hours. The same concentration of BSA was used as a control. Total RNA was extracted using an RNeasy Mini Kit (Qiagen). Single-stranded cDNA was synthesized from 0.5μg of total RNA using a PrimeScript RT reagent Kit (Takara Bio). Quantification of each gene expression was performed using the 7500 Fast Real-time PCR System (Applied Biosystems) by the intercalator method using specific primers and TB Green Fast qPCR Mix (Takara Bio). The expression level of each gene was corrected by the expression level of ribosomal protein S18 (RPS18), and the relative value was calculated with the expression level after treatment with BSA set to 1. The gene expression inhibition rate (%) of each sample was calculated using the following formula.

[0042]

number

[0043] In other words, the gene expression inhibition rate (%) is the percentage obtained by subtracting the relative value when palmitic acid was treated after sample treatment from the relative value when palmitic acid was treated alone, divided by the relative value when BSA was treated alone from the relative value when palmitic acid was treated alone.

[0044] The results are shown in the following table. In the study shown in Figure 2 (with test substance added), IL-6, CXCL1, ICAM-1, IL-8, TLR4, and CD36 were selected as various inflammatory cytokines, chemokines, adhesion factor genes, and receptor genes.

[0045] [Table 5]

[0046] TIFF2024095194000013.tif244170

[0047] TIFF2024095194000014.tif244170

[0048] TIFF2024095194000015.tif244170

[0049] TIFF2024095194000016.tif244170

[0050] TIFF2024095194000017.tif244170

Claims

1. A composition for improving lipid metabolism, comprising at least one member selected from the group consisting of calcium pantothenate, sodium pantothenate, protamine sulfate, and panthenol.

2. Contains at least one selected from the group consisting of ingredients listed in the table below: Composition for improving lipid metabolism. Table 1

3. The composition according to claim 1 or 2 for obese or diabetic patients.

4. 3. The composition of claim 1 or 2, which is an oral composition.

5. The composition according to claim 1 or 2, which is for preventing arteriosclerosis.

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