Journal article
OPA1 Regulates Lipid Metabolism and Cold-Induced Browning of White Adipose Tissue in Mice
Diabetes (New York, N.Y.), Vol.71(12), pp.2572-2583
09/28/2022
DOI: 10.2337/db22-0450
PMCID: PMC9750944
PMID: 36170659
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.
Details
- Title: Subtitle
- OPA1 Regulates Lipid Metabolism and Cold-Induced Browning of White Adipose Tissue in Mice
- Creators
- Renata O Pereira - Roy J. and Lucille A. Carver College of MedicineAngela C Olvera - Roy J. and Lucille A. Carver College of MedicineAlex Marti - Roy J. and Lucille A. Carver College of MedicineShi Fang - Roy J. and Lucille A. Carver College of MedicineJeffrey R White - Roy J. and Lucille A. Carver College of MedicineMichael Westphal - Roy J. and Lucille A. Carver College of MedicineRana Hewezi - Roy J. and Lucille A. Carver College of MedicineSalma T AshShareef - Roy J. and Lucille A. Carver College of MedicineLuis Miguel Garcia Pena - Roy J. and Lucille A. Carver College of MedicineJivan Koneru - Roy J. and Lucille A. Carver College of MedicineMatthew J Potthoff - Roy J. and Lucille A. Carver College of MedicineE Dale Abel - University of California, Los Angeles
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.71(12), pp.2572-2583
- DOI
- 10.2337/db22-0450
- PMID
- 36170659
- PMCID
- PMC9750944
- NLM abbreviation
- Diabetes
- eISSN
- 1939-327X
- Grant note
- DOI: 10.13039/100000050, name: National Heart, Lung, and Blood Institute, award: HL112413, HL127764; DOI: 10.13039/100000968, name: American Heart Association, award: 15SDG25710438
- Language
- English
- Date published
- 09/28/2022
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984302606702771
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