Phenotypic characterization of Adig null mice suggests roles for adipogenin in the regulation of fat mass accrual and leptin secretion
Anna Alvarez-Guaita,
Satish Patel,
Koini Lim,
Afreen Haider,
Liang Dong,
Olivia J. Conway,
Marcella K.L. Ma,
Davide Chiarugi,
Vladimir Saudek,
Stephen O’Rahilly,
David B. Savage
Affiliations
Anna Alvarez-Guaita
Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, Cambridgeshire CB2 0QQ, UK
Satish Patel
Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, Cambridgeshire CB2 0QQ, UK
Koini Lim
Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, Cambridgeshire CB2 0QQ, UK
Afreen Haider
Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, Cambridgeshire CB2 0QQ, UK
Liang Dong
Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, Cambridgeshire CB2 0QQ, UK
Olivia J. Conway
Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, Cambridgeshire CB2 0QQ, UK
Marcella K.L. Ma
MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Genomics and Transcriptomics Core, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
Davide Chiarugi
Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, Cambridgeshire CB2 0QQ, UK
Vladimir Saudek
Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, Cambridgeshire CB2 0QQ, UK
Stephen O’Rahilly
Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, Cambridgeshire CB2 0QQ, UK
David B. Savage
Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, Cambridgeshire CB2 0QQ, UK; Corresponding author
Summary: 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.