10E,12Z-conjugated linoleic acid impairs adipocyte triglyceride storage by enhancing fatty acid oxidation, lipolysis, and mitochondrial reactive oxygen species

J Lipid Res. 2013 Nov;54(11):2964-78. doi: 10.1194/jlr.M035188. Epub 2013 Aug 17.

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.

Keywords: carnitine palmitoyl transferase I; etomoxir; glucose uptake; inflammation; lipid metabolism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism*
  • Animals
  • Biological Transport / drug effects
  • Carnitine O-Palmitoyltransferase / genetics
  • Chemokines / genetics
  • Chemotaxis / drug effects
  • Gene Expression Regulation / drug effects
  • Glucose / metabolism
  • Linoleic Acids, Conjugated / metabolism
  • Linoleic Acids, Conjugated / pharmacology*
  • Lipolysis / drug effects*
  • Mice
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidation-Reduction / drug effects
  • Palmitates / pharmacology
  • Phenotype
  • Reactive Oxygen Species / metabolism*
  • Triglycerides / metabolism*

Substances

  • Chemokines
  • Linoleic Acids, Conjugated
  • Palmitates
  • Reactive Oxygen Species
  • Triglycerides
  • trans-10,cis-12-conjugated linoleic acid
  • Carnitine O-Palmitoyltransferase
  • Glucose