OPA1 Regulates Lipid Metabolism and Cold-Induced Browning of White Adipose Tissue in Mice

Diabetes. 2022 Dec 1;71(12):2572-2583. doi: 10.2337/db22-0450.

Abstract

Mitochondria play a vital role in white adipose tissue (WAT) homeostasis including adipogenesis, fatty acid synthesis, and lipolysis. We recently reported that the mitochondrial fusion protein optic atrophy 1 (OPA1) is required for induction of fatty acid oxidation and thermogenic activation in brown adipocytes. In the current study we investigated the role of OPA1 in WAT function in vivo. We generated mice with constitutive or inducible knockout of OPA1 selectively in adipocytes. Studies were conducted under baseline conditions, at thermoneutrality, following high-fat feeding or during cold exposure. OPA1 deficiency reduced mitochondrial respiratory capacity in white adipocytes, impaired lipolytic signaling, repressed expression of de novo lipogenesis and triglyceride synthesis pathways, and promoted adipose tissue senescence and inflammation. Reduced WAT mass was associated with hepatic triglycerides accumulation and glucose intolerance. Moreover, mice deficient for OPA1 in adipocytes had impaired adaptive thermogenesis and reduced cold-induced browning of subcutaneous WAT and were completely resistant to diet-induced obesity. In conclusion, OPA1 expression and function in adipocytes are essential for adipose tissue expansion, lipid biosynthesis, and fatty acid mobilization of WAT and brown adipocytes and for thermogenic activation of brown and beige adipocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipocytes, Brown / metabolism
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White* / metabolism
  • Animals
  • Cold Temperature
  • Fatty Acids / metabolism
  • Lipid Metabolism* / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mitochondrial Proteins / metabolism
  • Thermogenesis / genetics
  • Triglycerides / metabolism

Substances

  • Fatty Acids
  • Mitochondrial Proteins
  • Triglycerides