Chemerin Deficiency Regulates Adipogenesis Is Depot Different Through Timp1

Adipocytes and immune cells are vital for the development of adipose tissue.Adipokines secreted by adipocytes regulate adipogenesis and body metabolism.Chemerin is one of the adipokines which recruits numerous immune cells and exerts essential roles in adipogenesis and adipocyte metabolism.However,the function and mechanism of chemerin in adipose tissue in vivo are not fully illuminated.Compared with wild type?WT?mice,rarres2^-/-mice gained weight and significantly increased fat distribution in subcutaneous adipose tissue?SAT?,rather than visceral adipose tissue?VAT?on high fat diet?HFD?.PPAR? and C/EBP?,the master regulators of adipogenesis,were up-regulated in SAT and down-regulated in VAT in rarres2^-/-mice comparing with WT mice.Chemerin deficient or not,the ratio of adipocyte-progenitors to total cells and the differentiation capacity of adipocyte-progenitors were similar in SAT and VAT,but macrophage infiltration in VAT was more severe than in SAT in rarres2^-/-mice.Furthermore,CD45+ immune cells supernatant from rarres2^-/-SAT promoted the differentiation of adipocyte-progenitors and 3T3-L1 cells.Adipokine array assay of CD45+ immune cells supernatant revealed that metalloproteinase inhibitor 1?TIMP1?,an inhibitor of adipogenesis,was reduced in rarres2^-/-SAT,but increased in rarres2^-/-VAT.As we knocked down chemerin specific in SAT with adenovirus,TIMP1 was down-regulated and adipogenesis was promoted with reducing infiltration of macrophages.The present study demonstrates that the effects of chemerin on adipose tissue is depot different in vivo,and specific knock down chemerin in SAT could promote adipogenesis and improve glucose tolerance test?GTT?and insulin tolerance test?ITT?.This suggests a potential therapeutic target for chemerin in the treatment of obesity related metabolic disorder.Non-alcoholic fatty liver?NAFLD?is a syndrome characterized by excessive deposition of lipid in the liver caused by non-alcohol and other clear liver damage factors,which further develops into cirrhosis,liver failure and hepatocellular carcinoma.The basic pathological changes of NAFLD are lipid metabolism disorders and inflammatory reactions,and are closely related to other metabolic diseases,such as obesity and insulin resistance.NAFLD has gradually become a common disease.In this study,the adipokine chemerin was used to investigate the mechanism of the development of NAFLD.Under high-fat diet conditions,chemerin-deficient mice are more likely to be obese with NAFLD,liver inflammation levels are increased,glucose tolerance is reduced,and insulin resistance is enhanced.On the other hand,under normal diet condition,no differences were observed between chemerin-deficient mice and WT mice.The primary hepatocytes of chemerin-deficient mice in chemerin accumulated more lipids,and CD36 was significantly up-regulated.Next,knockdown CD36 through the tail vein can reverse NAFLD caused by chemerin deficiency under high-fat feeding conditions.The mechanism study found that chemerin deletion down-regulated ERK phosphorylation,stimulated the up-regulation of PPAR?,which in turn caused the up-regulation of CD36 expression and promoted the uptake of lipid by hepatocytes.This study found that the adipokine chemerin can participate in the formation of NAFLD by regulating the expression of CD36,which opens a new direction for the study of the pathogenesis of NAFLD.