Growth/differentiation factor 3 signals through ALK7 and regulates accumulation of adipose tissue and diet-induced obesity.
Growth/differentiation factor 3 (GDF3) is highly expressed in adipose tissue, and previous overexpression experiments in mice have suggested that it may act as an adipogenic factor under conditions of high lipid load. GDF3 has been shown to signal via the activin receptor ALK4 during embryogenesis, but functional receptors in adipose tissue are unknown. In this study, we show that Gdf3(-/-) mutant mice accumulate less adipose tissue than WT animals and show partial resistance to high-fat diet-induced obesity despite similar food intake. We also demonstrate that GDF3 can signal via the ALK4-homolog ALK7 and the coreceptor Cripto, both of which are expressed in adipose tissue. In agreement with a role for ALK7 in GDF3 signaling in vivo, mutant mice lacking ALK7 also showed reduced fat accumulation and partial resistance to diet-induced obesity. We propose that GDF3 regulates adipose-tissue homeostasis and energy balance under nutrient overload in part by signaling through the ALK7 receptor.
Andersson
Olov
O
Division of Molecular Neurobiology, Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm, Sweden.
Korach-Andre
Marion
M
Reissmann
Eva
E
Ibáñez
Carlos F
CF
Bertolino
Philippe
P
D030201:Activin Receptors, Type I / Q000502:physiology*; D000273:Adipose Tissue / Q000378:metabolism*; D000821:Animal Feed; D000818:Animals; D004032:Diet; D005786:Gene Expression Regulation; D055451:Growth Differentiation Factor 3; D006801:Humans; D007328:Insulin / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
C525974:GDF3 protein, human; C525975:Gdf3 protein, mouse; D055451:Growth Differentiation Factor 3; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; C424205:ACVR1C protein, human; D030201:Activin Receptors, Type I; C515277:Acvr1c protein, mouse