The Genetic Ablation of TNF-α Attenuates Wnt-Signaling and Adiposity in High Fat Diet-Induced Obese Mice

Abstract

A chronic low-grade inflammation is considered as a consequence of obesity, and linked with multiple complications. However, it is under-investigated how inflammatory cytokines mediate adipogenesis. This study investigated the role of Tumor Necrosis Factor α (TNF-α) on adipogenes is over high-fat diet feeding. Three groups of wild type or TNF-α-/mice with the same C57BL/6 genetic background were utilized in this study: wild type fed with a low-fat diet (WT-LFD), wild type fed with a high-fat diet (WT-HFD), and TNF-α-/fed with a HFD (TNF-HFD). After 16-wk feeding, inflammatory cytokine, Wnt pathway and adipogenesis-related genes were analyzed. HFD feeding increased body weight in both WTHFD and TNF-HFD groups, but genetic ablation of TNF-α attenuated HFD-induced obesity. In visceral adipose tissues, HFD elevated Wnt/β-catenin signaling, indicated by decreased phospho-GSK3β and active β-catenin, two key components within the Wnt pathway, and dysregulated adipogenesis, indicated by reduced PPARγ/CEBPα expressions. Whereas, the deletion of TNF-α suppressed Wnt-signaling, and restored expressions of adipogenes is-related genes, which were otherwise decreased in the HFD-induced obese animals. These findings demonstrated a critical role of TNF-α in the regulation of Wnt-signaling and adiposity in mice over a HFD feeding, indicating HFD-induced adipocyte dysfunction could be mitigated by targeting TNF-α and Wnt-signaling.