Growth differentiation factor 5 (GDF5) was reported to regulate brown adipogenesis, however, its effects on insulin sensitivity, full metabolic syndrome spectrum and the thermogenesis in subcutaneous white adipose tissue (sWAT) haven't been elucidated yet. We thus generated fatty acid-binding protein 4 (Fabp4)-GDF5 transgenic mice and showed that GDF5 transgenic mice developed a relative lean phenotype on a high-fat diet (HFD) and showed increased insulin sensitivity. Over expression of GDF5 in adipose tissues greatly promoted the thermogenic process in sWAT following cold or β3-agonist treatment. In transgenic mice, sWAT showed an important thermogenic effect as the thermogenic gene expression was markedly increased, which was consistent with the typical features of beige adipocytes. Enhanced MAPK/ATF2 signaling was also identified in sWAT of HFD-fed GDF5 mice, and thermogenesis in mature adipocytes induced by GDF5 protein could be partly blocked by a p38 MAPK inhibitor. Taken together, our data suggest that GDF5 could improve insulin sensitivity and prevent metabolic syndrome, the adaptive thermogenesis in sWAT could mediate the obesity resistance effects of GDF5 in mice and partially resulted in the activation of the p38 MAPK signaling pathway.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology