Impaired resting muscle energetics studied by 31P-NMR in diet-induced obese rats

Abstract

Objective:Mitochondrial activity is altered in skeletal muscle of obese, insulin-resistant or type 2 diabetic patients. We hypothesized that this situation was associated with profound adaptations in resting muscle energetics. For that purpose, we used in vivo 31P-nuclear magnetic resonance (31P-NMR) in male sedentary Wistar rats fed with obesogenic diets known to induce alterations in muscle mitochondrial activity.Methods and Procedures:Two experimental diets (high sucrose and high fat) were provided for 6 weeks at two levels of energy (standard, N and high, H) and compared to control diet. The rates of the adenosine triphosphate (ATP) exchange between phosphocreatine (PCr) and -ATP (k(a)) and Β-adenosine diphosphate (Β-ADP) to Β-ATP (k(b)) were evaluated using 31P-NMR in resting gastrocnemius muscle. Muscle contents in phosphorylated compounds as well as creatine, were assessed using 31P-NMR and biochemical assays, respectively.Results:ATP content increased by 6.7-8.5 in standard-energy high-sucrose (NSU), high-energy high-fat (HF) and high-energy high-sucrose (HSU) groups compared to control (P < 0.05), whereas PCr content decreased by 4.2-6.4 (P < 0.01). Consequently, PCr to ATP ratio decreased in NSU, HF, and HSU groups, compared to control (P < 0.01). Furthermore in high-energy groups (HF and HSU) compared to control, creatine contents were decreased by 14-19 (P < 0.001), whereas k(a) and k(b) fluxes were increased by 89-133 (P < 0.001) and 243-277 (P < 0.01), respectively.Discussion:Our in vivo data showed adaptations of resting skeletal muscle energetics in response to high-energy diets. Increased activity of enzymes catalyzing ATP production may reflect a compensatory mechanism to face impaired mitochondrial ATP synthesis in order to preserve intracellular energy homeostasis. © 2008 The Obesity Society.