Location: Children's Nutrition Research Center
Title: GDF5 promotes white adipose tissue thermogenesis via p38 MAPK signaling pathwayAuthor
ZHANG, WENTING - Fudan University | |
WU, XIAOHUI - Fudan University | |
PEI, ZHOU - Fudan University | |
KIESS, WIELAND - University Of Leipzig | |
YANG, YAN - Fudan University | |
XU, YONG - Children'S Nutrition Research Center (CNRC) | |
CHANG, ZHUO - Fudan University | |
WU, JING - Fudan University | |
SUN, CHENGJUN - Fudan University | |
LUO, FEIHONG - Fudan University |
Submitted to: DNA and Cell Biology
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 10/3/2019 Publication Date: 11/1/2019 Citation: Zhang, W., Wu, X., Pei, Z., Kiess, W., Yang, Y., Xu, Y., Chang, Z., Wu, J., Sun, C., Luo, F. 2019. GDF5 promotes white adipose tissue thermogenesis via p38 MAPK signaling pathway. DNA and Cell Biology 38(11):1303-1312. https://doi.org/10.1089/dna.2019.4724 DOI: https://doi.org/10.1089/dna.2019.4724 Interpretive Summary: Obesity and associated insulin resistance are a serious global health problem. GDF5 has been shown to regulate body weight but its role in insulin sensitivity is not clear. Here we showed that GDF5 can improve insulin sensitivity and prevent metabolic syndrome. These findings suggested that GDF5 and its associated signals could be potential targets for treatment of obesity and diabetes. Technical Abstract: 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) have not been elucidated yet. We thus generated fatty acid-binding protein 4 (Fabp4)-GDF5 transgenic (TG) mice and showed that GDF5 TG 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 after cold or ß3-agonist treatment. In TG 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. Moreover, knockdown of the protein GDF5 impaired browning program in sWAT after thermogenic stimuli. Enhanced mitogen-activated protein kinase (MAPK)/activating transcription factor 2 (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. |