title: 10E,12Z-conjugated linoleic acid impairs adipocyte triglyceride storage by enhancing fatty acid oxidation, lipolysis, and mitochondrial reactive oxygen species.
abstract: Conjugated linoleic acid (CLA) is a naturally occurring dietary trans fatty acid found in food from ruminant sources. One specific CLA isomer, 10E,12Z-CLA, has been associated with health benefits, such as reduced adiposity, while simultaneously promoting deleterious effects, such as systemic inflammation, insulin resistance, and dyslipidemia. The precise mechanisms by which 10E,12Z-CLA exerts these effects remain unknown. Despite potential health consequences, CLA continues to be advertised as a natural weight loss supplement, warranting further studies on its effects on lipid metabolism. We hypothesized that 10E,12Z-CLA impairs lipid storage in adipose tissue by altering the lipid metabolism of white adipocytes. We demonstrate that 10E,12Z-CLA reduced triglyceride storage due to enhanced fatty acid oxidation and lipolysis, coupled with diminished glucose uptake and utilization in cultured adipocytes. This switch to lipid utilization was accompanied by a potent proinflammatory response, including the generation of cytokines, monocyte chemotactic factors, and mitochondrial superoxide. Disrupting fatty acid oxidation restored glucose utilization and attenuated the inflammatory response to 10E,12Z-CLA, suggesting that fatty acid oxidation is critical in promoting this phenotype. With further investigation into the biochemical pathways involved in adipocyte responses to 10E,12Z-CLA, we can discern more information about its safety and efficacy in promoting weight loss.
authors: Diabetes Obesity Center for Excellence and the Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA 98109.
authors: Laura J
authors: LJ
authors: den Hartigh
authors: Chang Yeop
authors: CY
authors: Han
authors: Shari
authors: S
authors: Wang
authors: Mohamed
authors: M
authors: Omer
authors: Alan
authors: A
authors: Chait
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D018925:Chemokines / Q000235:genetics; D002633:Chemotaxis / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000378:metabolism / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010168:Palmitates / Q000494:pharmacology; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D018925:Chemokines; D044243:Linoleic Acids, Conjugated; D010168:Palmitates; D017382:Reactive Oxygen Species; D014280:Triglycerides; C496197:trans-10,cis-12-conjugated linoleic acid; D002334:Carnitine O-Palmitoyltransferase; D005947:Glucose
keywords: carnitine palmitoyl transferase I; etomoxir; glucose uptake; inflammation; lipid metabolism
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