Distinct roles of TRAF6 and TAK1 in the regulation of adipocyte survival, thermogenesis program, and high-fat diet-induced obesity.

Distinct roles of TRAF6 and TAK1 in the regulation of adipocyte survival, thermogenesis program, and high-fat diet-induced obesity. Oncotarget. 2017 Dec 22;8(68):112565-112583 Authors: Gallot YS, McMillan JD, Xiong G, Bohnert KR, Straughn AR, Hill BG, Kumar A Abstract Chronic low-grade inflammation, adipocyte hypertrophy, and glucose intolerance are common features of obesity and a risk factor for cancer. Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is an adaptor protein that also possesses a non-conventional E3 ubiquitin ligase activity. In response to receptor-mediated events, TRAF6 activates transforming growth factor-activated kinase 1 (TAK1), which leads to activation of the MAPK and nuclear factor-kappa B (NF-κB) signaling pathways. However, the roles of TRAF6 and TAK1 in the regulation of adipocyte function remain less understood. Here, we demonstrate that adipocyte-specific deletion of TAK1, but not TRAF6, in mice reduces the survival of adipocytes and abundance of white adipose tissue (WAT). Adipocyte-specific ablation of TAK1, but not TRAF6, increases the expression for markers of beige/brown fat in WAT. Deletion of TAK1 in WAT increases phosphorylation of AMPK, abundance of PGC-1α, non-canonical NF-κB signaling, markers of M2 macrophages, and diminishes phosphorylation of JNK and canonical NF-κB signaling. Levels of TRAF6 and enzymatic activity of TAK1 are increased in WAT of mice fed with high-fat ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research