The Role Of PNPLA7 In Mouse Adipose Tissue

Objective:By using PNPLA7 adipose tissue specific transgenic mouse(aP2-PNPLA7Tg)as a model system,we aim to invesitage the role of PNPLA7 protein in white adipose tissue(WAT)and brown adipose tissue(BAT),and its influence on adipocyte differentiation and lipid metabolism.Methods:After generated adipose tissue specific PNPLA7 transgenic mice(aP2-PNPLA7Tg),we performed subcelluar fractionation,real-time PCR,western blot,metabolic cage,glucose and insulin intolerance test and phenotypic analysis to identify subcelluar location of PNPLA7 protein,andverify the phenotype of aP2-PNPLA7Tg in aspects of adipocyte differentiation,lipid metabolism and inflammation.Results:Murine PNPLA7 protein is localized in the endoplasmic reticulum.Under normal diet condition,compared with wild-type mice,the adiposity index of aP2-PNPLA7Tg mice are reduced,but insulin sensitivity are not changed;Furthermore,whole body metabolism and thermogenesis function are enhanced in aP2-PNPLA7Tg mice.The number and size of adipocyte is reduced significantly in WAT of aP2-PNPLA7Tg.Moreover,the synthesis of fatty acids is blocked,especially inhibits the expression of triglyceride synthetase.Therefore,there is dyslipidemia in the circulation.After high fat diet treatment,aP2-PNPLA7Tg mice are not resistant to high-fat diet induced obesity,due to impairedfatty acid oxidationin BAT,accompanied by inflammation in WAT.As a consequence,insulin sensitivity and glucose metabolism are impaired and eventually lead to ectopic lipid accumulation in liver.In addition,fatty acid overload could weaken the inhibition influenced by PNPLA7 during the process of adipocyte differentiation.Consistently,macrophage infiltration combined with chronic inflammation may trigger necrosis in adipocytes.Finally,adipokines'malfunction will result in whole body metabolic disorder.Conclusion:Overexpression of PNPLA7 in adipose tissue will inhibit adipocyte differentiation and impaired lipid metabolism in adipose tissue.Thus,our study may provide a potential pharmaceutical target for the NAFLD and metabolic disorder.