UCP1 deficiency increases adipose tissue monounsaturated fatty acid synthesis and trafficking to the liver

• Published in: Journal of lipid research Vol. 59; no. 2; pp. 224 - 236
• Main Authors: Bond, Laura M., Ntambi, James M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2018; Journal of Lipid Research; The American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: Adipocytes; Adipose tissue; Adipose tissue (brown); Adipose Tissue - chemistry; Adipose Tissue - metabolism; animal models; Animals; brown adipocytes; brown adipose tissue; cell communication; cold stress; Desaturase; Energy expenditure; epididymis; fatty acid metabolism; fatty acid/desaturases; Fatty Acids, Monounsaturated - chemistry; Fatty Acids, Monounsaturated - metabolism; Gene expression; glucose transporters; heat production; hepatic; Homeostasis; Housing; Hyperplasia; knockout mutants; lipid; Lipids; Lipogenesis; Lipolysis; Liver; Liver - chemistry; Liver - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria; mitochondrial membrane; palmitoleic acid; Stearoyl-CoA desaturase; Stearoyl-CoA Desaturase - genetics; Stearoyl-CoA Desaturase - metabolism; Thermogenesis; Transcription activation; transcriptional activation; triacylglycerols; Uncoupling Protein 1 - deficiency; Uncoupling Protein 1 - metabolism; white adipose tissue; β-oxidation; β-oxidation; hepatic; thermogenesis; fatty acid/metabolism; fatty acid/desaturases; lipid
• ISSN: 0022-2275; 1539-7262; 1539-7262
• DOI: 10.1194/jlr.M078469

Uncoupling protein-1 (UCP1) facilitates thermogenesis in brown and beige adipocytes and can promote energy expenditure by decreasing mitochondrial respiratory efficiency. Defects in UCP1 and brown adipose tissue thermogenesis subject animals to chronic cold stress and elicit compensatory responses to generate heat. How UCP1 regulates white adipose tissue (WAT) lipid biology and tissue crosstalk is not completely understood. Here, we probed the effect of UCP1 deficiency on FA metabolism in inguinal and epididymal WAT and investigated how these metabolic perturbations influence hepatic lipid homeostasis. We report that at standard housing temperature (21°C), loss of UCP1 induces inguinal WAT de novo lipogenesis through transcriptional activation of the lipogenic gene program and elevated GLUT4. Inguinal adipocyte hyperplasia and depot expansion accompany the increase in lipid synthesis. We also found that UCP1 deficiency elevates adipose stearoyl-CoA desaturase gene expression, and increased inguinal WAT lipolysis supports the transport of adipose-derived palmitoleate (16:1n7) to the liver and hepatic triglyceride accumulation. The observed WAT and liver phenotypes were resolved by housing animals at thermoneutral housing (30°C). These data illustrate depot-specific responses to impaired BAT thermogenesis and communication between WAT and liver in UCP1−/− mice.