Study On The Effect Of OLGly On Feeding In Mice And Its Mechanism

Lipoamino acids or N-acyl amino acids?NAAAs?are endogenoussubstances produced from the fatty acid conjugation of amino acids,which are widely distributed in human and livestocks and other mammalian tissues.Present studies have revealed that NAAAs play an important role in the regulation of vasodilatation,neuroprotection and inflammation.However,the effects of NAAAs on food intake andenergy homeostasis are still unknown.WechosethreecommonNAAAs?N-arachidonoylglycine,NAGly;N-arachidonoylserine,NASer and N-oleoylglycine,OLGly?to test the the effects of NAAAs on food intake of C57/BL6J mice and neurotransmitter release of hypothalamic N38 cell lines.Subsequently,the effects of O LGly on the food intake of mice in different energy states were observed,and we used the elevated-plus maze?EPM?and open field test?OFT?to observe the anxiety behavior of mice;we also analyzed the effects of O LGly on the expression of neurotransmitters,calcium-related pathway proteins and cannabinoid receptors in hypothalamus and N38 cells and the concentration of[Ca²⁺]_i,secretion of AgRP and expression of c-Fos.Our results showed that,only O LGly can effectively induce hyperphagia at 24 h among 3 NAAAs?NAGly,NASer and OLGly?.Besides,OLGly could improve the food intake of mice at 24 h?P<0.05?,but had no effect on the food consumption of high fat diet?HFD??P>0.05?.And O LGly can promoted the mRNA expression of AgRPsignificantly,but had no effects on the protein expression of hypothalamic neuropeptides?AgRP,NPY and POMC?and the mRNA expression of NPY,POMC and MC4R.The results of behavioral analysis showed that the effect of O LGly on hyperphagia was not caused by the anxiety behavior of mice.Our vitro results showed that OLGly could increase the concentration of[Ca²⁺]_iin N38 cells,while NAGly and NASer had no effect.Besides,OLGly promoted the secretion of AgRP in N38 cells.After treated with O LGly for 30 min,the expression of c-Fos was improved,but the expression of PKA and CREB didn't change.The effects of OLGly on[Ca²⁺]_i,expression of c-Fos and secretion of AgRP in N38 cells were reversed effectively after co-treated with CB1 receptor antagonist and OLGly.Above all,our results showed that OLGly through the CB1 receptor activated AgRP neurons,which probably the reason of O LGly inducinghyperphagia.