| G-Protein Coupled Receptors (GRCRs) also known as seven-transmembrane domain receptors is a group of G protein-linked receptors, which were essential for the onset of many diseases. G-Protein Coupled Receptors120(GPR120) is a newly identified member in this group; previous studies showed this protein played a role in regulating secretion of gastrointestinal hormones, generating of lipid, adiposities differentiation and mediating anti-inflammatory effects. By studying the effects of long-chain fatty acids with different structures on regulation of GLP-1in the intestinal endocrine cells STC-1through GPR120, and the improvement of GLP-1, Glucose and lipid level in high fat diet feed mice with the supplement of flaxseed oil, we showed that long-chain fatty acids could regulate the secretion of GLP-1through GRP120. This study may provide a new target for the prevention and treatment of diabetes mellitus.Experiments in cell line:GPR120mediate the increased cell activity,[Ca2+]i signal change and GLP-1secretion induced by free lipids. The effect of long-chain monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) on the improvement of serum-starved STC-1cell viability was more significant than long-chain saturated fatty acids; high concentration of long-chain MUFA and PUFA inhibited the activity of caspase-3in starved STC-1cells; the addition of alpha-linolenic acid and linoleic acid significantly increased the expression of GPR120; long-chain fatty acid improve the survival and proliferation of STC cells by the activation of PI3K/AKT pathway.In vivo experiments:Mice in the HFD group were fed with60%fat diet; in the FOD group, mice were also fed with60%fat diet, but flaxseed oil was used instead of15%lard. After4weeks, body weight of mice in HFD group and FOD group were significantly higher than the ND group fed with normal diet; fasting blood glucose was increased in mice of HFD group and FOD group; fasting insulin in mice of HFD group was significantly higher than that in FOD group, along with insulin resistance; supplement of flaxseed oil improved blood glucose confirmed by IPGTT and ITT test; the concentration of plasma GLP-1was higher in mice of FOD group than the other groups; fasting TC, TG and LDL in mice of FOD group were lower than that of HFD group, and no significant difference with ND group, suggesting the supplement of flaxseed oil could reduce the blood lipid in mice.After8weeks, mice in HFD group and FOD group all reached the standard of obese or overweight, weight of lipid tissue and pancreas were significantly higher than that in ND group; fasting blood glucose in mice of HFD group was significantly higher than that in ND and FOD group; fasting insulin in mice of HFD group and FOD group was higher than that of ND group; in IPGTT test, the increase of blood glucose in mice of FOD group was lower than that of HFD group; in ITT test, there was no significant difference of blood glucose between FOD group and HFD group; blood lipid in mice of FOD was lower with less lipid deposit in the liver, suggesting a protection role of flaxseed oil in lipid metabolism; the concentration of plasma GLP-1was significantly increased in HFD and FOD groups, and the expression of Gpr120mRNA was increased in both lipid tissue and intestinal tissue, suggesting the increased GPR120might facilitate the secretion of GLP-1, and subsequently decrease blood glucose; in addition, the supplement of flaxseed oil decreased the expression of M1and M2anti-inflammatory protein.In all, long-chain lipid acid increased cell proliferation, GLP-1secretion,[Ca2+]i signal change through GPR120, the effect of linoleic acid was similar to that of alpha-linolenic acid. In mice model of insulin resistance induced by high lipid diet, supplement of flaxseed oil rich in n-3fatty acid improve the metabolism of glucose and lipid, stimulated the secretion of GLP-1and reduced the expression of inflammatory factors in fat and liver. |
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