| First Author | Tse MCL | Year | 2017 |
| Journal | Diabetes | Volume | 66 |
| Issue | 7 | Pages | 1858-1870 |
| PubMed ID | 28404596 | Mgi Jnum | J:246943 |
| Mgi Id | MGI:5924360 | Doi | 10.2337/db16-0270 |
| Citation | Tse MCL, et al. (2017) Tumor Necrosis Factor-alpha Promotes Phosphoinositide 3-Kinase Enhancer A and AMP-Activated Protein Kinase Interaction to Suppress Lipid Oxidation in Skeletal Muscle. Diabetes 66(7):1858-1870 |
| abstractText | Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine that plays a central role in obesity-induced insulin resistance. It also controls cellular lipid metabolism, but the underlining mechanism is poorly understood. We report in this study that phosphoinositide 3-kinase enhancer A (PIKE-A) is a novel effector of TNF-alpha to facilitate its metabolic modulation in the skeletal muscle. Depletion of PIKE-A in C2C12 myotubes diminished the inhibitory activities of TNF-alpha on mitochondrial respiration and lipid oxidation, whereas PIKE-A overexpression exacerbated these cellular responses. We also found that TNF-alpha promoted the interaction between PIKE-A and AMP-activated protein kinase (AMPK) to suppress its kinase activity in vitro and in vivo. As a result, animals with PIKE ablation in the skeletal muscle per se display an upregulation of AMPK phosphorylation and a higher preference to use lipid as the energy production substrate under high-fat diet feeding, which mitigates the development of diet-induced hyperlipidemia, ectopic lipid accumulation, and muscle insulin resistance. Hence, our data reveal PIKE-A as a new signaling factor that is important for TNF-alpha-initiated metabolic changes in skeletal muscle. |
