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Deficiency of Growth Differentiation Factor 3 Protects against Diet-Induced Obesity by Selectively Acting on White Adipose

Children’s Hospital of Central California (J.J.S.), Madera, California 93636; Departments of Molecular and Human Genetics (L.H., C.J., M.M.M., C.W.B.), Pathology (M.M.M.), Molecular and Cellular Biology (M.M.M.), and Pediatrics (C.W.B.), Baylor College of Medicine, and Department of Pediatrics (L.L.), M.D. Anderson Cancer Center, Houston, Texas 77030

Address all correspondence and requests for reprints to: Chester W. Brown, Department of Molecular and Human Genetics, Baylor College of Medicine 225, Room R717, One Baylor Plaza, Houston, Texas 77030. E-mail: cbrown{at}bcm.edu.

Growth differentiation factor 3 (GDF3) is a member of the TGFβ superfamily. White adipose is one of the tissues in which Gdf3 is expressed, and it is the only tissue in which expression increases in response to high-fat diet. We generated Gdf3^–/– mice, which were indistinguishable from wild-type mice and had normal weight curves on regular diet. However, on high-fat diet Gdf3^–/– mice were resistant to the obesity that normally develops in wild-type mice. Herein we investigate the physiological and molecular mechanisms that underlie this protection from diet-induced obesity and demonstrate that GDF3 deficiency selectively affects white adipose through its influence on basal metabolic rates. Our results are consistent with a role for GDF3 in adipose tissue, with consequential effects on energy expenditure that ultimately impact adiposity.