Conjugated Linoleic Acid Induces Human Adipocyte Delipidation: Autocrine/Paracrine Regulation Of Mek/Erk Signaling By Adipocytokines

Authors

J. Mark Brown, Department of Nutrition, University of North Carolina at Greensboro, Greensboro, North Carolina
Maria Sandberg Boysen, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense DK-5230, Denmark
Soonkyu Chung, Department of Food Science and Human Nutrition, University of Florida, Gainesville, FLFollow
Olowatoyin Fabiyi, Department of Nutrition, University of North Carolina at Greensboro, Greensboro, North Carolina
Ron F. Morrison, Department of Nutrition, University of North Carolina at Greensboro, Greensboro, North Carolina
Susanne Mandrup, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense DK-5230, Denmark
Michael K. McIntosh, Department of Nutrition, University of North Carolina at Greensboro, Greensboro, North Carolina

Document Type

Article

Date of this Version

2004

Citation

J Biol Chem. 2004 June 18; 279(25): 26735–26747.

Comments

Used by permission.

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 CLAmediated 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.