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Am J Physiol Endocrinol Metab 277: E830-E837, 1999;
0193-1849/99 $5.00
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Vol. 277, Issue 5, E830-E837, November 1999

Lack of skeletal muscle uncoupling protein 2 and 3 mRNA induction during fasting in type-2 diabetic subjects

Hubert Vidal1, Dominique Langin2, Fabrizio Andreelli1,3, Laurence Millet2, Dominique Larrouy2, and Martine Laville1,3

1 Institut National de la Santé et de la Recherche Médicale Unit 449 and Centre de Recherche en Nutrition Humaine de Lyon, Faculté de Médecine René Laënnec, 69372 Lyon; 2 Institut National de la Santé et de la Recherche Médicale Unit 317, Institut Louis Bugnard, Université Paul Sabatier, Hôpital Rangueil, 31403 Toulouse; and 3 Service d'Endocrinologie, Diabétologie et Nutrition, Hôpital E. Herriot, 69437 Lyon, France.

Skeletal muscle uncoupling protein 2 and 3 (UCP-2 and UCP-3) mRNA levels are increased during calorie restriction in lean and nondiabetic obese subjects. In this work, we have investigated the effect of a 5-day hypocaloric diet (1,045 kJ/day) on UCP-2 and UCP-3 gene expression in the skeletal muscle of type-2 diabetic obese patients. Before the diet, UCP-2 and UCP-3 mRNA levels were more abundant in diabetic than in nondiabetic subjects. The long (UCP-3L) and short (UCP-3S) forms of UCP-3 transcripts were expressed at similar levels in nondiabetic subjects, but UCP-3S transcripts were twofold more abundant than UCP-3L transcripts in the muscle of diabetic patients. Calorie restriction induced a two- to threefold increase in UCP-2 and UCP-3 mRNA levels in nondiabetic patients. No change was observed in type-2 diabetic patients. Variations in plasma nonesterified fatty acid level were positively correlated with changes in skeletal muscle UCP-3L (r = 0.6, P < 0.05) and adipose tissue hormone-sensitive lipase (r = 0.9, P < 0.001) mRNA levels. Lack of increase in plasma nonesterified fatty acid level and in hormone-sensitive lipase upregulation in diabetic patients during the diet strengthens the hypothesis that fatty acids are associated with the upregulation of uncoupling proteins during calorie restriction.

obesity; calorie restriction; nonesterified fatty acid; lipolysis


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