| First Author | Turpin-Nolan SM | Year | 2019 |
| Journal | Cell Rep | Volume | 26 |
| Issue | 1 | Pages | 1-10.e7 |
| PubMed ID | 30605666 | Mgi Jnum | J:284081 |
| Mgi Id | MGI:6380950 | Doi | 10.1016/j.celrep.2018.12.031 |
| Citation | Turpin-Nolan SM, et al. (2019) CerS1-Derived C18:0 Ceramide in Skeletal Muscle Promotes Obesity-Induced Insulin Resistance. Cell Rep 26(1):1-10.e7 |
| abstractText | Skeletal muscle accumulates ceramides in obesity, which contribute to the development of obesity-associated insulin resistance. However, it remained unclear which distinct ceramide species in this organ contributes to instatement of systemic insulin resistance. Here, ceramide profiling of high-fat diet (HFD)-fed animals revealed increased skeletal muscle C18:0 ceramide content, concomitant with increased expression of ceramide synthase (CerS)1. Mice lacking CerS1, either globally or specifically in skeletal muscle (CerS1(DeltaSkM)), exhibit reduced muscle C18:0 ceramide content and significant improvements in systemic glucose homeostasis. CerS1(DeltaSkM) mice exhibit improved insulin-stimulated suppression of hepatic glucose production, and lack of CerS1 in skeletal muscle improves systemic glucose homeostasis via increased release of Fgf21 from skeletal muscle. In contrast, muscle-specific deficiency of C16:0 ceramide-producing CerS5 and CerS6 failed to protect mice from obesity-induced insulin resistance. Collectively, these results reveal the tissue-specific function of distinct ceramide species during the development of obesity-associated insulin resistance. |
