DEPP Deficiency Contributes To Browning Of White Adipose Tissues

Over-accumulation of white fat can cause obesity,type 2 diabetes,metabolic syndrome and other diseases.Promoting BAT-like features in white adipose is an attractive therapeutic approach for the treatment of obesity and diabetesOur previous study has indicated,DEPP as a novel FXR target gene,whose expression continued to rise during adipogenesis.DEPP-depleted 3T3-L1 cells showed significantly delayed adipocyte differentiation and lipid accumulation,compared with control 3T3-L1 cells,and selectively decreased representative white genes Angiotensinogen(agt),resistin,Wdnm1L,and Itga6.However,DEPP-depleted brown adipose cell selectively increased mRNA amounts of the BAT-selective genes,including COX8b?Dio2 andPRDM16.Which indicate that DEPP can regulate the white adipocyte differentiation,and adjust its conversion to brown adipocyte.In order to explain the relationship between DEPP and adipocyte differentiation on molecular level,we studied the interaction between DEPP and several regulators of adipocyte differentiation.We performed co-immunoprecipitation(CO-IP)to testify the interaction between DEPP?PPAR ? and Sirt1.Furthermore,we show that DEPP can competitive inhibit the combination of Sirtl and PPAR ? and depress the deacetylation of SirT1.DEPP-/-MEFs show no difference in adipocyte differentiation,but selectively increased mRNA amounts of the BAT-selective genes.We next investigated the metabolic correlates of our findings.DEPP-/-mice under a high-fat diet improve glucose intolerant without body weight changes.To validate our finding,we surveyed adipose tissues in DEPP-/-mice after triggering thermogenesis by cold exposure.We saw increased numbers of Ucpl immunoreactive paucilocular iWAT adipocytes,together with increased expression of brown genes,suggestive of a"browning" of subcutaneous white adipocytes.Taken together,our study demonstrates a novel function of DEPP,plays a critical role in regulating adipogenesis.DEPP not only affects the differentiation of white adipocyte,but also regulates the transformation of white adipocytes to brown adipocytes.Our current study will reveal a new pathway and mechanism for adipocyte differentiation,and targeting DEPP might improve therapies for obesity and metabolic complication.