title: Conjugated linoleic acid induces human adipocyte delipidation: autocrine/paracrine regulation of MEK/ERK signaling by adipocytokines.
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.
authors.affiliation: Department of Nutrition, University of North Carolina at Greensboro, Greensboro, North Carolina 27402-6170, USA.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Brown
authors.forename: Maria Sandberg
authors.initials: MS
authors.lastname: Boysen
authors.forename: Soonkyu
authors.initials: S
authors.lastname: Chung
authors.forename: Olowatoyin
authors.initials: O
authors.lastname: Fabiyi
authors.forename: Ron F
authors.initials: RF
authors.lastname: Morrison
authors.forename: Susanne
authors.initials: S
authors.lastname: Mandrup
authors.forename: Michael K
authors.initials: MK
authors.lastname: McIntosh
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D050356:Lipid Metabolism; D020935:MAP Kinase Signaling System; D008856:Microscopy, Fluorescence; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D009570:Nitriles / Q000494:pharmacology; D019301:Oleic Acid / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014280:Triglycerides / Q000737:chemistry
chemical_list: D002070:Butadienes; D016207:Cytokines; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D016209:Interleukin-8; D044243:Linoleic Acids, Conjugated; D009570:Nitriles; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides; C113580:U 0126; D019301:Oleic Acid; D012313:RNA; D037342:Pertussis Toxin; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D005947:Glucose