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journal contribution
posted on 2019-03-04, 16:51 authored by Weiqin ChenBscl2−/− 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.