University Hospital CHU of Guadeloupe, Pointe à Pitre, 97110, France.
EA7525, University of the French West Indies, Fort de France, 97159, France.
Appl Physiol Nutr Metab. 2020 Oct;45(10):1107-1117. doi: 10.1139/apnm-2019-0936. Epub 2020 Apr 14.
Accumulation of advanced glycation end products (AGEs) and activation of the receptor for AGEs (RAGE) are 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 the effects of AGE/RAGE axis activation on skeletal muscle oxidative stress and metabolism are more limited. We tested whether a high-fat diet (HFD) would alter circulating AGE concentration, skeletal muscle AGE accumulation, and oxidative stress in wild-type and RAGE-deficient mice. The physiological significance of AGE/RAGE axis activation in HFD-fed mice was evaluated in terms of exercise tolerance and mitochondrial respiratory chain complex activity. HFD elicited adiposity, abnormal fat distribution, and oral glucose intolerance. HFD also induced accumulation of -carboxymethyl-l-lysine, increased protein carbonyl levels, and impaired respiratory chain complex activity in soleus muscle. Ablation of RAGE had no effects on weight gain and oral glucose tolerance in HFD-fed mice. Peak aerobic capacity and mitochondrial cytochrome- oxidase activity were restored in HFD-fed RAGE mice. We concluded that RAGE signaling plays an important role in skeletal muscle homeostasis of mice under metabolic stress. HFD in mice induces accumulation of AGEs, oxidative stress, and mitochondrial dysfunction in the soleus muscle. RAGE, the multi-ligand receptor for AGEs, modulates oxidative stress and mitochondrial electron transport chain function in the soleus muscle of HFD-fed mice.
糖基化终产物 (AGEs) 的积累和 AGEs 受体 (RAGE) 的激活与衰老、慢性炎症、糖尿病和细胞应激相关病理的进展有关。RAGE 激活也与 2 型糖尿病的心血管并发症有关，如肾病、视网膜病变、加速血管疾病和心肌病。研究 AGE/RAGE 轴激活对骨骼肌氧化应激和代谢的影响较为有限。我们测试了高脂肪饮食 (HFD) 是否会改变循环 AGE 浓度、骨骼肌 AGE 积累和野生型和 RAGE 缺陷型小鼠的氧化应激。从运动耐量和线粒体呼吸链复合物活性方面评估了 AGE/RAGE 轴激活在 HFD 喂养小鼠中的生理意义。HFD 引起肥胖、脂肪分布异常和口服葡萄糖耐量异常。HFD 还诱导 -羧甲基-l-赖氨酸积累、增加蛋白质羰基水平，并损害比目鱼肌中的呼吸链复合物活性。RAGE 的缺失对 HFD 喂养小鼠的体重增加和口服葡萄糖耐量没有影响。HFD 喂养的 RAGE 小鼠的峰值有氧能力和线粒体细胞色素 c 氧化酶活性得到恢复。我们得出结论，RAGE 信号在代谢应激下的小鼠骨骼肌稳态中发挥重要作用。HFD 在小鼠中诱导 AGEs 的积累、氧化应激和比目鱼肌中的线粒体功能障碍。RAGE 是 AGEs 的多配体受体，调节 HFD 喂养小鼠比目鱼肌中的氧化应激和线粒体电子传递链功能。
