Conjugated linoleic acid induces human adipocyte delipidation: autocrine/paracrine regulation of MEK/ERK signaling by adipocytokines

J Biol Chem. 2004 Jun 18;279(25):26735-47. doi: 10.1074/jbc.M401766200. Epub 2004 Apr 2.

Abstract

Dietary conjugated linoleic acid (CLA) reduces body fat in animals and some humans. Here we show that trans-10, cis-12 CLA, but not cis-9, trans-11 CLA, when added to cultures of stromal vascular cells containing newly differentiated human adipocytes, caused a time-dependent decrease in triglyceride content, insulin-stimulated glucose and fatty acid uptake, incorporation into lipid, and oxidation compared with controls. In parallel, gene expression of peroxisome proliferator-activated receptor-gamma and many of its downstream targets were diminished by trans-10, cis-12 CLA, whereas leptin gene expression was increased. Prior to changes in gene expression and metabolism, trans-10, cis-12 CLA caused a robust and sustained activation of mitogen-activated protein kinase kinase/extracellular signal-related kinase (MEK/ERK) signaling. Furthermore, the trans-10, cis-12 CLA-mediated activation of MEK/ERK could be attenuated by pretreatment with U0126 and pertussis toxin. In parallel, pretreatment with U0126 blocked the ability of trans-10, cis-12 CLA to alter gene expression and attenuate glucose and fatty acid uptake of the cultures. Intriguingly, the induction by CLA of MEK/ERK signaling was linked to hypersecretion of adipocytokines interleukin-6 and interleukin-8. Collectively, these data demonstrate for the first time that trans-10, cis-12 CLA decreases the triglyceride content of newly differentiated human adipocytes by inducing MEK/ERK signaling through the autocrine/paracrine actions of interleukins-6 and 8.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Butadienes / pharmacology
  • Cell Differentiation
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Cytokines / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation
  • Glucose / metabolism
  • Humans
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Linoleic Acids, Conjugated / pharmacology*
  • Lipid Metabolism*
  • MAP Kinase Signaling System
  • Microscopy, Fluorescence
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Models, Biological
  • Nitriles / pharmacology
  • Oleic Acid / metabolism
  • Pertussis Toxin / pharmacology
  • RNA / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Time Factors
  • Transcription Factors / metabolism
  • Triglycerides / chemistry

Substances

  • Butadienes
  • Cytokines
  • Enzyme Inhibitors
  • Interleukin-6
  • Interleukin-8
  • Linoleic Acids, Conjugated
  • Nitriles
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Triglycerides
  • U 0126
  • Oleic Acid
  • RNA
  • Pertussis Toxin
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • Glucose