Lack of skeletal muscle uncoupling protein 2 and 3 mRNA induction during fasting in type-2 diabetic subjects.
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-3(L)) and short (UCP-3(S)) forms of UCP-3 transcripts were expressed at similar levels in nondiabetic subjects, but UCP-3(S) transcripts were twofold more abundant than UCP-3(L) 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-3(L) (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.
Vidal
H
H
Institut National de la Santé et de la Recherche Médicale Unit 449 Lyon, France. langin@rangueil.inserm.fr
Langin
D
D
Andreelli
F
F
Millet
L
L
Larrouy
D
D
Laville
M
M
D002352:Carrier Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D002149:Energy Intake; D005215:Fasting / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007473:Ion Channels; D008066:Lipolysis / Q000502:physiology; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000201:enzymology*; D009765:Obesity / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D002787:Sterol Esterase / Q000032:analysis; D014158:Transcription, Genetic / Q000502:physiology; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D002787:Sterol Esterase