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Journal of Lipid Research, Vol. 48, 2236-2246, October 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Acute exposure to long-chain fatty acids impairs ₂-adrenergic receptor-mediated antilipolysis in human adipose tissue

Jan Polak^*, Cédric Moro^*,,, David Bessière^*,,, Jindra Hejnova^*, Marie A. Marquès^*,, Magda Bajzova^*, Max Lafontan^1,*,,**, Francois Crampes^*,, Michel Berlan^*,, and Vladimir Stich^*

^* Franco-Czech Laboratory for Clinical Research on Obesity, French Institute of Health and Medical Research (Institut National de la Santé et de la Recherche Médicale U858) and Third Medical Faculty, Charles University in Prague, Prague, Czech Republic
French Institute of Health and Medical Research (Institut National de la Santé et de la Recherche Médicale U858), Institute of Molecular Medicine Rangueil, Institut Fédératif de Recherches 31 Louis Bugnard Institute, Toulouse, France
Faculty of Medicine Purpan, Laboratory of Medical and Clinical Pharmacology, Toulouse, France
^** Paul Sabatier University, Toulouse, France

Published, JLR Papers in Press, July 11, 2007.

¹ To whom correspondence should be addressed. e-mail: max.lafontan{at}toulouse.inserm.fr

The acute in vitro and in vivo effects of long-chain fatty acids (LCFAs) on the regulation of adrenergic lipolysis were investigated in human adipose tissue. The effect of a 2 h incubation, without or with LCFA (200 µmol/l), on basal and hormonally induced lipolysis was tested in vitro on isolated fat cells. The lipolytic response to epinephrine was enhanced by suppression of the antilipolytic ₂-adrenergic effect. Then, healthy lean and obese male subjects performed a 45 min exercise bout at 50% of their heart rate reserve either after an overnight fast or 3 h after a high-fat meal (HFM: 95% fat, 5% carbohydrates). Subcutaneous adipose tissue lipolysis was measured by microdialysis in the presence or absence of an -antagonist (phentolamine). In vivo, a HFM increased plasma levels of nonesterified fatty acids in lean and obese subjects. In both groups, the HFM did not alter hormonal responses to exercise. Under fasting conditions, the ₂-adrenergic antilipolytic effect was more pronounced in obese than in lean subjects. The HFM totally suppressed the ₂-adrenergic antilipolytic effect in lean and obese subjects during exercise. LCFAs per se, in vitro as well as in vivo, suppress ₂-adrenergic-mediated antilipolysis in adipose tissue. LCFA-mediated suppression of antilipolytic pathways represents another mechanism whereby a high fat content in the diet might increase adipose tissue lipolysis.

Supplementary key words lipolysis • catecholamines • high-fat meal • exercise • microdialysis • lipid mobilization

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