Andersson Olov, Korach-Andre Marion, Reissmann Eva, Ibáñez Carlos F, Bertolino Philippe
Division of Molecular Neurobiology, Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm, Sweden.
Proc Natl Acad Sci U S A. 2008 May 20;105(20):7252-6. doi: 10.1073/pnas.0800272105. Epub 2008 May 14.
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.
生长/分化因子3（GDF3）在脂肪组织中高度表达，先前在小鼠中的过表达实验表明，在高脂负荷条件下它可能作为一种脂肪生成因子发挥作用。已表明GDF3在胚胎发育过程中通过激活素受体ALK4进行信号传导，但脂肪组织中的功能性受体尚不清楚。在本研究中，我们发现Gdf3基因敲除突变小鼠比野生型动物积累的脂肪组织更少，尽管食物摄入量相似，但对高脂饮食诱导的肥胖表现出部分抗性。我们还证明，GDF3可通过ALK4同源物ALK7和共受体Cripto进行信号传导，二者均在脂肪组织中表达。与ALK7在体内GDF3信号传导中的作用一致，缺乏ALK7的突变小鼠也表现出脂肪积累减少和对饮食诱导肥胖的部分抗性。我们提出，GDF3部分通过ALK7受体信号传导来调节营养过剩情况下的脂肪组织稳态和能量平衡。
