Identification of meteorin and metrnl as two novel pro-differentiative adipokines: Possible roles in controlling adipogenesis and insulin sensitivity

Abstract

Meteorin and its homologue meteorin-like (metrnl) are two novel proteins regulating glial cell differentiation in central nervous system. However, the roles of meteorin and metrnl in other organs or tissues have never been studied. In this study, we showed that meteorin and metrnl were expressed abundantly in white adipose, including visceral and subcutaneous adipose tissues, but to a much lesser extent in brown adipose tissue. Meteorin and metrnl were found to be secreted by explanted human white fat pads, 3T3-L1 preadipocytes and differentiated 3T3-L1 adipocytes. Moreover, meteorin and metrnl were detected in human blood by immunoblotting assay. The mRNA expression of meteorin and metrnl increased along with the 3T3-L1 cells differentiation. Overexpression of meteorin and metrnl using adenovirus promoted the formation of lipid droplets, increased PPARγ protein expression and enhanced mRNA expression of several other adipogenic genes in 3T3-L1 adipocytes. Injection of adipose-specific aP2-promoter driven adenovirus expressing meteorin and metrnl markedly improved global insulin sensitivity and reversed insulin resistance induced by high fat diet in mice. At last, overexpression of meteorin and metrnl further magnified the phosphorylation of Akt upon insulin stimuli in 3T3-L1 cells. Collectively, our data suggests that meteorin and metrnl are two novel pro-differentiative adipokines participating in adipogenesis and regulation of insulin sensitivity. © 2013 Elsevier Inc. All rights reserved.