The role of Repin1 in adipose tissue

Replication initiator 1 (Repin1) is a polydactyl zinc finger protein organized in three clusters, located on human chromosome 7 and on chromosome 6 in mice. The protein of Repin1 is ubiquitous expressed but maximum mRNA levels were detected in liver and adipose tissue. Repin1 maps in a quantitative trait locus (QTL) which is associated with obesity and triglyceride levels. Therefore it has been suggested as a candidate gene for obesity and its related metabolic disorders in congenic and subcongenic rat strains. To dissect the role of Repin1 in adipose tissue we generated two different adipose tissue specific Repin1 deficient mice: a conditional (ARep1^-/) and an inducible (iARep1^-/-) knockout of Repin1 to investigate the effects of early and late ablation of the gene. Both knockout models have been extensively phenotyped including body weight gain, determination of insulin and glucose tolerance, organ weight, fat cell size and lipid profile. For both knockout models, conditional and inducible, we obtained (I) reduced body weight in males, (II) decreased relative fat mass and a small fat cell size in males, (III) increased liver weight independently of sex (IV) decreased lipid values in males and (V) increased insulin tolerance independently of sex. (VI) Glucose tolerance was only improved in the inducible knockout model. In conclusion, those findings indicate that Repin1 plays a key role in adipogenesis and lipid metabolism. Furthermore, alterations of Repin1 expression lead to dyslipidemia and subsequent impairment of glucose homeostasis.