Decreased mitochondrial proton leak and reduced expression of uncoupling protein 3 in skeletal muscle of obese diet-resistant XXXX .

@entity1 @entity353 @entity13514 @entity1629 @entity5912
Weight loss in response to caloric restriction is variable. Because skeletal muscle mitochondrial proton leak may account for a large proportion of resting metabolic rate, we compared proton leak in diet-resistant and diet-responsive overweight @entity1 and compared the expression and gene characteristics of @entity5912 and @entity13514 . Of 1,129 overweight @entity1 who completed the University of Ottawa Weight Management Clinic program, 353 met compliance criteria and were free of medical conditions that could affect @entity353 . Subjects were ranked according to percent body @entity353 during the first 6 weeks of a 900-kcal meal replacement protocol. The highest and lowest quintiles of @entity353 were defined as diet responsive and diet resistant, respectively. After body weight had been stable for at least 10 weeks, 12 of 70 subjects from each group consented to muscle biopsy and blood sampling for determinations of proton leak, @entity1629 mRNA expression, and genetic studies. Despite similar baseline weight and age, @entity353 was 43% greater, mitochondrial proton leak-dependent (state 4) respiration was 51% higher (P = 0.0062), and expression of @entity13514 mRNA abundance was 25% greater (P < 0.001) in diet-responsive than in diet-resistant subjects. There were no differences in @entity5912 mRNA abundance. None of the known polymorphisms in @entity13514 or its 5' flanking sequence were associated with @entity353 or @entity13514 mRNA abundance. Thus, proton leak and the expression of @entity13514 correlate with @entity353 success and may be candidates for pharmacological regulation of fat oxidation in obese diet-resistant subjects.
