Effects Of Pentadecanoic Acid On Glucose Metabolism And Its Mechanism

Glucose metabolism discorder is a key risk factor which causes diabetes.Saturated long chain fatty acids Palmitic acid and stearic acid have a negative impact on glucose metabolism and increase the risk of type 2 diabetes,but different dietary fatty acids have different effects on glucose metabolism and the occurrence and development of diabetes mellitus,which depend on their chain length and saturation.Though the preliminary screening for compound from hypoglycemic plants,we found that pentadecanoic acid has a very significant effect on promoting glucose consumption of the cells.It suggested that pentadecanoic acid may play a role in regulating glucose metabolism.The effect and mechanism of pentadecanoic acid as long-chain fatty acids on glucose metabolism is unclear.In this study,we systematically evaluated the effect of pentadecanoic acid on glucose metabolism on cells and the whole body level of animals,and the mechanism was discussed.The aim of this study was to clarify the regulation effects of pentadecanoic acid on glucose metabolism and its target,in order to provide experimental basis for comprehensive understanding the different functions of long chain fatty acids.And it provides a theoretical basis for reasonable intake of dietary fatty acids.In terms of the cellular model,we found that different concentrations of pentadecanoic acid significantly promoted the glucose consumption of 3T3-L1 adipocytes at a basic level and is concentration-dependence,which is consistent with the results shows in C2C12 myotubes.We found that the combination of pentadecanoic acid and insulin in 3T3-L1 adipocytes or C2C12 myotubes has a much more stronger effect on glucose consumption than using insulin alone.We then investigated the possible mechanism of pentadecanoic acid promoting glucose consumption.We found that at the basal level,pentadecanoic acid had no significant effect on the protein level of CAP,ERK,PPARy,PPARβ,PPARa.Skeletal muscle cells had verified this result.But it was able to significantly reduce the expression of P-ERK,P-PPARγ(Ser112),and the combination of insulin in the myotubes also has a consistent result,indicating that pentadecanoic acid can reduce phosphorylation of ERK and then improve the activity of PPARγ,which may play a certain role in promoting cell glucose consumption.We also found that pentadecanoic acid in both cells reduced the phosphorylation of IRS,PI3K and AKT,but pentadecanoic acid enhanced phosphorylation of AMPK and phosphorylation of P38 which is downstream of AMPK.What is more,it increased the phosphorylation of AS 160 and the expression of membrane protein Glut4.This result is again validated by the combination of insulin.The difference is that pentadecanoic acid in skeletal muscle cells can significantly increase the expression of P-PKC(ζ/λ),but it is not found in adipocytes.In summary,pentadecanoic acid promotes cell glucose consumption by increasing the activity of AMPK,which activates P3 8,and then promotes the activity of downstream AS 160,leading to the transport of membrane protein Glut4.We used the AMPK inhibitor Compound C to prove the result.It was found that Compound C reverses the glucose consumption promoted by pentadecanoic acid and reverses the phosphorylation of AS 160,aPKC,P38 and AMPK promoted by pentadecanoic acid.We used Compound C to prove that pentadecanoic acid promoted the glucose consumption through the AMPK pathway.In terms of animal model,we used high fat diet and STZ-induced type 2 diabetes mellitus mice to observe the effect of pentadecanoic acid on glucose metabolism in type 2 diabetic mice.First,we found that pentadecanoic acid has no significant impact on drinking water,diet and weight in type 2 diabetes mice.Secondly,pentadecanoic acid has no significant effect on fasting blood glucose,glycosylated hemoglobin and insulin resistance.However,pentadecanoic acid can reduce the level of serum insulin,improve hyperinsulinemia and inhibit the inflammatory factor TNF-a.Pentadecanoic acid prevent the destruction of diabetes on pancreatic islet cells observed by HE staining.Pentadecanoic acid has no significant effect on high and low density lipoprotein cholesterol,triglycerides,and free fatty acids in terms of lipid metabolism,which is associated with glucose metabolism disorders,but it can significantly reduce the weight of epididymal fat pads and serum total cholesterol.In summary,pentadecanoic acid is mainly through the AMPK pathway to promote glucose consumption in cells.Pentadecanoic acid does not affect fasting blood glucose levels,but can improve hyperinsulinemia and protect islet cells in type 2 diabetic mice.What is more,it can also reduce serum cholesterol,fat accumulation and improve the inflammation of diabetic mice.