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This Article Full Text Full Text (PDF) Supplemental Figures and Tables All Versions of this Article: 295/2/E356    most recent 90256.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kus, V. Articles by Kopecky, J. PubMed PubMed Citation Articles by Kus, V. Articles by Kopecky, J.

Induction of muscle thermogenesis by high-fat diet in mice: association with obesity-resistance

Vladimir Kus,¹ Tomas Prazak,¹ Petr Brauner,¹ Michal Hensler,¹ Ondrej Kuda,¹ Pavel Flachs,¹ Petra Janovska,¹ Dasa Medrikova,¹ Martin Rossmeisl,¹ Zuzana Jilkova,¹ Bohumir Stefl,^4, Eva Pastalkova,³ Zdenek Drahota,² Josef Houstek,² and Jan Kopecky¹

Departments of ¹Adipose Tissue Biology, ²Bioenergetics, and ³Neurophysiology of Memory and Computational Neuroscience, Institute of Physiology, Academy of Sciences of the Czech Republic; and ⁴Department of Physiology and Developmental Biology, Faculty of Science, Charles University, Prague, Czech Republic

Submitted 27 February 2008 ; accepted in final form 20 May 2008

The obesogenic effect of a high-fat (HF) diet is counterbalanced by stimulation of energy expenditure and lipid oxidation in response to a meal. The aim of this study was to reveal whether muscle nonshivering thermogenesis could be stimulated by a HF diet, especially in obesity-resistant A/J compared with obesity-prone C57BL/6J (B/6J) mice. Experiments were performed on male mice born and maintained at 30°C. Four-week-old mice were randomly weaned onto a low-fat (LF) or HF diet for 2 wk. In the A/J LF mice, cold exposure (4°C) resulted in hypothermia, whereas the A/J HF, B/6J LF, and B/6J HF mice were cold tolerant. Cold sensitivity of the A/J LF mice was associated with a relatively low whole body energy expenditure under resting conditions, which was normalized by the HF diet. In both strains, the HF diet induced uncoupling protein-1-mediated thermogenesis, with a stronger induction in A/J mice. Only in A/J mice: 1) the HF diet augmented activation of whole body lipid oxidation by cold; and 2) at 30°C, oxygen consumption, total content, and phosphorylation of AMP-activated protein kinase (AMPK), and AICAR-stimulated palmitate oxidation in soleus muscle was increased by the HF diet in parallel with significantly increased leptinemia. Gene expression data in soleus muscle of the A/J HF mice indicated a shift from carbohydrate to fatty acid oxidation. Our results suggest a role for muscle nonshivering thermogenesis and lipid oxidation in the obesity-resistant phenotype of A/J mice and indicate that a HF diet could induce thermogenesis in oxidative muscle, possibly via the leptin-AMPK axis.

nonshivering thermogenesis; leptin; adenosine monophosphate-activated protein kinase