Novel metabolic disorders in skeletal muscle of Lipodystrophic Bscl2/Seipin deficient mice

Wenqiong Xu, Hongyi Zhou, Hongzhuan Xuan, Pradip Saha, Gongxian Wang, Weiqin Chen

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume482
DOIs
StatePublished - Feb 15 2019

Keywords

  • BSCL2
  • Hyperinsulinemic-euglycemic clamp
  • Insulin resistance
  • Lipodystrophy
  • Skeletal muscle

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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