| First Author | Xu W | Year | 2019 |
| Journal | Mol Cell Endocrinol | Volume | 482 |
| Pages | 1-10 | PubMed ID | 30521848 |
| Mgi Jnum | J:273218 | Mgi Id | MGI:6286580 |
| Doi | 10.1016/j.mce.2018.12.001 | Citation | Xu W, et al. (2019) Novel metabolic disorders in skeletal muscle of Lipodystrophic Bscl2/Seipin deficient mice. Mol Cell Endocrinol 482:1-10 |
| abstractText | Bscl2(-/-) mice recapitulate many of the major metabolic manifestations in Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) individuals, including lipodystrophy, hepatosteatosis, muscular hypertrophy, and insulin resistance. Metabolic defects in Bscl2(-/-) mice with regard to glucose and lipid metabolism in skeletal muscle have never been investigated. Here, we identified Bscl2(-/-) mice displayed reduced intramyocellular triglyceride (IMTG) content but increased glycogen storage predominantly in oxidative type I soleus muscle (SM). These changes were associated with increased incomplete fatty acid oxidation and glycogen synthesis. Interestingly, SM in Bscl2(-/-) mice demonstrated a fasting duration induced insulin sensitivity which was further confirmed by hyperinsulinemic-euglycemic clamp in SM of overnight fasted Bscl2(-/-) mice but reversed by raising circulating NEFA levels through intralipid infusion. Furthermore, mice with skeletal muscle-specific inactivation of BSCL2 manifested no changes in muscle deposition of lipids and glycogen, suggesting BSCL2 does not play a cell-autonomous role in muscle lipid and glucose homeostasis. Our study uncovers a novel link between muscle metabolic defects and insulin resistance, and underscores an important role of circulating NEFA in regulating oxidative muscle insulin signaling in BSCL2 lipodystrophy. |
