New findings show that inhibition of activin receptor type IIB (ActRIIB)—a signalling receptor for TGFβ ligands—can suppress the development of obesity in mice fed a high-fat diet (HFD). Treating HFD-fed mice with the novel antibody ActRIIB-Fc (a form of the ActRIIB extracellular domain fused to a human IgG Fc domain) resulted in significantly increased lean tissue mass, prevented HFD-induced alterations in serum hormones and lipids, and prevented lipid accumulation in liver and brown fat. Further analyses showed that protection from diet-induced obesity was due to increased energy expenditure associated with elevated expression of thermogenesis genes in white adipose tissue. The researchers identified several TGFβ ligands, including GDF-8 and GDF-11, which mediated these effects of ActRIIB-Fc. Targeting these ligands could be a novel treatment strategy for obesity, they conclude.
ORIGINAL RESEARCH PAPER
Koncarevic, A. et al. A novel therapeutic approach to treating obesity through modulation of TGFβ signaling. Endocrinology doi:10.1210/en.2012-1016
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TGFβ ligands: novel targets for obesity treatment?. Nat Rev Endocrinol 8, 384 (2012). https://doi.org/10.1038/nrendo.2012.82
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DOI: https://doi.org/10.1038/nrendo.2012.82