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Originally published In Press as doi:10.1194/jlr.M600393-JLR200 on October 18, 2006

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Journal of Lipid Research, Vol. 48, 444-452, February 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Maintenance of adiponectin attenuates insulin resistance induced by dietary conjugated linoleic acid in mice

Aparna Purushotham, Angela A. Wendel1, Li-Fen Liu1 and Martha A. Belury2

Department of Human Nutrition, Ohio State University, Columbus, OH 43210

Published, JLR Papers in Press, October 18, 2006.

1 A. A. Wendel and L-F. Liu contributed equally to this work.

2 To whom correspondence should be addressed. e-mail: belury.1{at}osu.edu

Conjugated linoleic acid (CLA) causes insulin resistance and hepatic steatosis in conjunction with depletion of adipokines in some rodent models. Our objective was to determine whether the maintenance of adipokines, mainly leptin and adiponectin, by either removing CLA from diets or using an adiponectin enhancer, rosiglitazone (ROSI), could attenuate CLA-induced insulin resistance. Male C57BL/6 mice were consecutively fed two experimental diets containing 1.5% CLA mixed isomer for 4 weeks followed by a diet without CLA for 4 weeks. CLA significantly depleted adiponectin but not leptin and was accompanied by hepatic steatosis and insulin resistance. These effects were attenuated after switching mice to the diet without CLA along with restoration of adiponectin. To further elucidate the role of adiponectin in CLA-mediated insulin resistance, ROSI was used in a subsequent study in male ob/ob mice fed either control (CON) or CLA diet. ROSI maintained significantly higher adiponectin levels in CON- and CLA-fed mice and prevented the depletion of epididymal adipose tissue and the development of insulin resistance. In conclusion, we show that insulin resistance induced by CLA may be related more to adiponectin depletion than to leptin and that maintaining adiponectin levels alone either by removing CLA or using ROSI can attenuate these effects.

Supplementary key words hepatic steatosis • adipokines • hepatic steatosis • rosiglitazone

Abbreviations: AOX, acetyl-coenzyme A oxidase; CLA, conjugated linoleic acid; c9t11, cis9,trans11; CON, control; FBG, fasting blood glucose; IL-6, interleukin-6; PPAR{gamma}, peroxisome proliferator-activated receptor {gamma}; ROSI, rosiglitazone; TG, triglyceride; TNF-{alpha}, tumor necrosis factor-{alpha}


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