Phenotypic characterization of Adig null mice suggests roles for adipogenin in the regulation of fat mass accrual and leptin secretion

Adipogenin (Adig) is an adipocyte-enriched transmembrane protein. Its expression is induced during adipogenesis in rodent cells, and a recent genome-wide association study associated body mass index (BMI)-adjusted leptin levels with the ADIG locus. In order to begin to understand the biological function of Adig, we studied adipogenesis in Adig-deficient cultured adipocytes and phenotyped Adig null (Adig−/−) mice. Data from Adig-deficient cells suggest that Adig is required for adipogenesis. In vivo, Adig−/− mice are leaner than wild-type mice when fed a high-fat diet and when crossed with Ob/Ob hyperphagic mice. In addition to the impact on fat mass accrual, Adig deficiency also reduces fat-mass-adjusted plasma leptin levels and impairs leptin secretion from adipose explants, suggesting an additional impact on the regulation of leptin secretion. [Display omitted] •The absence of Adig impairs adipogenesis in vitro•High-fat diet (HFD)-induced weight gain is ameliorated in Adig−/− mice•Fat-mass-adjusted leptin levels are reduced in Adig−/− mice•Leptin secretion is reduced in Adig−/− adipose explants Alvarez-Guaita et al. show that Adipogenin (Adig) deficiency impairs adipogenesis in cultured cells. High-fat diet (HFD)-induced weight gain is ameliorated in Adig−/− mice, and fat-mass-adjusted leptin levels are lower. Leptin secretion from Adig−/− adipose explants is also reduced, suggesting that Adig influences leptin secretion.