RECEPTOR FOR ADVANCED GLYCATED END PRODUCTS MODULATES OXIDATIVE STRESS AND MITOCHONDRIAL FUNCTION IN THE SOLEUS MUSCLE OF HIGH FAT FED MICE

• Published in: Applied physiology, nutrition, and metabolism
• Main Authors: Velayoudom-Cephise, Fritz Line, Cano Sanchez, Mariola, Bercion, Sylvie, Tessier, Frederic, Yu, Yichi, Boulanger, Eric, Neviere, Remi
• Format: Journal Article
• Language: English
• Published: Canada 14.04.2020
• ISSN: 1715-5320

Background Accumulation of advanced glycation end products (AGE) and activation of receptor to AGE (RAGE) is implicated in the progression of pathologies associated with aging, chronic inflammation, diabetes and cellular stress. RAGE activation is also implicated in cardiovascular complications of type 2 diabetes, such as nephropathy, retinopathy, accelerated vascular diseases and cardiomyopathy. Studies investigating effects of AGE/RAGE axis activation on skeletal muscle oxidative stress / metabolism are more limited. Methods and Results We tested whether high fat feeding (HFD) would alter circulating AGE concentration, skeletal muscle AGE accumulation, and oxidative stress in wild type and RAGE deficient mice. Physiological significance of AGE/RAGE axis activation in mice under HFD was evaluated in terms of exercise tolerance, and mitochondrial respiratory chain complex activity. HFD elicited adiposity, abnormal fat distribution as well as oral glucose intolerance. HFD induced soleus muscle accumulation of Nɛ-carboxymethyl-lysine, increased carbonyl protein levels and impaired respiratory chain complex activity. Ablation of RAGE had no effects on weight gain and oral glucose tolerance in HFD mice. Peak exercise aerobic capacity and mitochondrial cytochrome c oxidase activity were restored in HFD RAGE-/- mice. Conclusions We concluded that RAGE signaling plays an important role in skeletal muscle homeostasis of mice under metabolic stress. Novelty bullets • High fat diet (HFD) in mice induces accumulation of advanced glycation end products (AGE), oxidative stress and mitochondrial dysfunction in the soleus muscle. • RAGE, the multi-ligand receptor of AGE, modulates oxidative stress and mitochondrial electron transport chain function in the soleus of HFD mice.