| First Author | Zumbaugh MD | Year | 2021 |
| Journal | Front Physiol | Volume | 12 |
| Pages | 682052 | PubMed ID | 34326778 |
| Mgi Jnum | J:312789 | Mgi Id | MGI:6729032 |
| Doi | 10.3389/fphys.2021.682052 | Citation | Zumbaugh MD, et al. (2021) Skeletal Muscle O-GlcNAc Transferase Action on Global Metabolism Is Partially Mediated Through Interleukin-15. Front Physiol 12:682052 |
| abstractText | Besides its roles in locomotion and thermogenesis, skeletal muscle plays a significant role in global glucose metabolism and insulin sensitivity through complex nutrient sensing networks. Our previous work showed that the muscle-specific ablation of O-GlcNAc transferase (OGT) led to a lean phenotype through enhanced interleukin-15 (IL-15) expression. We also showed OGT epigenetically modified and repressed the Il15 promoter. However, whether there is a causal relationship between OGT ablation-induced IL-15 secretion and the lean phenotype remains unknown. To address this question, we generated muscle specific OGT and interleukin-15 receptor alpha subunit (IL-15ralpha) double knockout mice (mDKO). Deletion of IL-15ralpha in skeletal muscle impaired IL-15 secretion. When fed with a high-fat diet, mDKO mice were no longer protected against HFD-induced obesity compared to wild-type mice. After 22 weeks of HFD feeding, mDKO mice had an intermediate body weight and glucose sensitivity compared to wild-type and OGT knockout mice. Taken together, these data suggest that OGT action is partially mediated by muscle IL-15 production and provides some clarity into how disrupting the O-GlcNAc nutrient signaling pathway leads to a lean phenotype. Further, our work suggests that interfering with the OGT-IL15 nutrient sensing axis may provide a new avenue for combating obesity and metabolic disorders. |
