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§ and
- Michael K. McIntosh‡¶
- ‡Department of Nutrition, University of North Carolina at Greensboro, Greensboro, North Carolina 27402-6170 and the §Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense DK-5230, Denmark
- ↵¶ To whom correspondence should be addressed: Dept. of Nutrition, 318 Stone Bldg., University of North Carolina at Greensboro, Greensboro, NC 27402-6170. Tel.: 336-256-0325; Fax: 336-334-4129; E-mail: mkmcinto{at}uncg.edu.
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.
- Received February 17, 2004.
- Revision received March 25, 2004.
- The American Society for Biochemistry and Molecular Biology, Inc.
