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

J. Mark Brown, Maria Sandberg Boysen, Soonkyu Chung, Olowatoyin Fabiyi, Ron F. Morrison, Susanne Mandrup, Michael K. McIntosh

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

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-γ 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.

Original languageEnglish (US)
Pages (from-to)26735-26747
Number of pages13
JournalJournal of Biological Chemistry
Volume279
Issue number25
DOIs
StatePublished - Jun 18 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Conjugated linoleic acid induces human adipocyte delipidation: Autocrine/paracrine regulation of MEK/ERK signaling by adipocytokines'. Together they form a unique fingerprint.

Cite this