Repin1 deficiency in adipose tissue improves whole-body insulin sensitivity, and lipid metabolism

Background/Objectives: Replication initiator 1 (Repin1) gene encodes for a zinc-finger protein and has been implicated in the regulation of adipocyte cell size and glucose transport in vitro . Here, we investigate the consequences of reduced adipose tissue (AT) Repin1 expression in vivo . Subjects/Methods: We have inactivated the Repin1 gene in adipose tissue (iARep −/− ) at an age of 4 weeks using tamoxifen-inducible gene targeting strategies on the background of C57BL/6NTac mice. Furthermore, we differentiated human primary adipocytes derived from subcutaneous AT in vitro and knocked down REPIN1 using siRNA technique to measure glycerol release. Results: Conditional Repin1 inactivation results in decreased AT mass, smaller adipocytes in both, subcutaneous and epigonadal AT compared to controls. Compared to controls, iARep −/− mice were more insulin sensitive, had better glucose tolerance and lower LDL-, HDL- and total cholesterol. Significantly lower AT expression of the Repin1 target genes Cd36 and Lcn2 may contribute to the phenotype of iARep −/− mice. Knockdown of REPIN1 in human in vitro differentiated adipocytes revealed an increased glycerol release. Conclusions: In conclusion, deficiency of Repin1 in AT causes alterations in AT morphology and function, which may underlay lower body weight and improved parameters of insulin sensitivity, glucose and lipid metabolism.