Adipocytes and immune cells are vital for the development of adipose tissue.Adi-pokines secreted by adipocytes regulate adipogenesis and body metabolism.Chemerin is one of the adipokines.However,the function and mecha...Adipocytes and immune cells are vital for the development of adipose tissue.Adi-pokines secreted by adipocytes regulate adipogenesis and body metabolism.Chemerin is one of the adipokines.However,the function and mechanism of chemerin in adipose tissue 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).PPARg and C/EBPa,the master regulators of adipogenesis,were up-regulated in SAT and down-regulated in VAT in Rarres2^(-/-)mice comparing with WT mice.Inspite of chemerin deficiency 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,CD45þimmune cells supernatant from Rarres2^(-/-)SAT pro-moted the differentiation of adipocyte-progenitors and 3T3-L1 cells.Adipokine array assay of CD45þimmune cells supernatant revealed that metalloproteinase inhibitor 1(TIMP1),an in-hibitor of adipogenesis,was reduced in Rarres2^(-/-)SAT,but increased in Rarres2^(-/-)VAT.As we specifically knocked down chemerin in SAT,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,and specific knock down chemerin in SAT 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.展开更多
基金Fund from Joint International Research Laboratory of Reproduction and Development,Institute of Life Science,Chongqing Medical University.National Key R&D Program of China[grant numbers 2018YFA0800401 to X.Li]National Natural Science Foundation of China[grant numbers 81770861 and 31571401 to X.Li]+3 种基金Chongqing Science and Technology Foundation[grant number cstc2018jcy-jAX0232]Science and Technology Research Program of Chongqing Municipal Education Commission[grant number KJZD-K201800402]The Outstanding Talent Fund of Chongqing Medical University[grant number BJRC201707]Chongqing education committee[grant number CYB17105].
文摘Adipocytes and immune cells are vital for the development of adipose tissue.Adi-pokines secreted by adipocytes regulate adipogenesis and body metabolism.Chemerin is one of the adipokines.However,the function and mechanism of chemerin in adipose tissue 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).PPARg and C/EBPa,the master regulators of adipogenesis,were up-regulated in SAT and down-regulated in VAT in Rarres2^(-/-)mice comparing with WT mice.Inspite of chemerin deficiency 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,CD45þimmune cells supernatant from Rarres2^(-/-)SAT pro-moted the differentiation of adipocyte-progenitors and 3T3-L1 cells.Adipokine array assay of CD45þimmune cells supernatant revealed that metalloproteinase inhibitor 1(TIMP1),an in-hibitor of adipogenesis,was reduced in Rarres2^(-/-)SAT,but increased in Rarres2^(-/-)VAT.As we specifically knocked down chemerin in SAT,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,and specific knock down chemerin in SAT 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.