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.