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

Author:

Vidal Hubert1,Langin Dominique2,Andreelli Fabrizio13,Millet Laurence2,Larrouy Dominique2,Laville Martine13

Affiliation:

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.

Abstract

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-3Ltranscripts 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.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

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