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Succinate induces skeletal muscle fiber remodeling via SUNCR1 signaling.
EMBO Reports ( IF 6.5 ) Pub Date : 2019-07-18 , DOI: 10.15252/embr.201947892 Tao Wang 1 , Ya-Qiong Xu 1 , Ye-Xian Yuan 1 , Ping-Wen Xu 2 , Cha Zhang 1 , Fan Li 1 , Li-Na Wang 1 , Cong Yin 1 , Lin Zhang 1 , Xing-Cai Cai 1 , Can-Jun Zhu 1 , Jing-Ren Xu 1 , Bing-Qing Liang 1 , Sarah Schaul 2 , Pei-Pei Xie 1 , Dong Yue 1 , Zheng-Rui Liao 1 , Lu-Lu Yu 1 , Lv Luo 1 , Gan Zhou 1 , Jin-Ping Yang 1 , Zhi-Hui He 1 , Man Du 1 , Yu-Ping Zhou 1 , Bai-Chuan Deng 1 , Song-Bo Wang 1 , Ping Gao 1 , Xiao-Tong Zhu 1 , Qian-Yun Xi 1 , Yong-Liang Zhang 1 , Gang Shu 1, 3 , Qing-Yan Jiang 1, 3
EMBO Reports ( IF 6.5 ) Pub Date : 2019-07-18 , DOI: 10.15252/embr.201947892 Tao Wang 1 , Ya-Qiong Xu 1 , Ye-Xian Yuan 1 , Ping-Wen Xu 2 , Cha Zhang 1 , Fan Li 1 , Li-Na Wang 1 , Cong Yin 1 , Lin Zhang 1 , Xing-Cai Cai 1 , Can-Jun Zhu 1 , Jing-Ren Xu 1 , Bing-Qing Liang 1 , Sarah Schaul 2 , Pei-Pei Xie 1 , Dong Yue 1 , Zheng-Rui Liao 1 , Lu-Lu Yu 1 , Lv Luo 1 , Gan Zhou 1 , Jin-Ping Yang 1 , Zhi-Hui He 1 , Man Du 1 , Yu-Ping Zhou 1 , Bai-Chuan Deng 1 , Song-Bo Wang 1 , Ping Gao 1 , Xiao-Tong Zhu 1 , Qian-Yun Xi 1 , Yong-Liang Zhang 1 , Gang Shu 1, 3 , Qing-Yan Jiang 1, 3
Affiliation
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The conversion of skeletal muscle fiber from fast twitch to slow-twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber-type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss-of-function models generated by phospholipase Cβ antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius-specific knockdown, we found that the effects of succinate on skeletal muscle fiber-type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate-based compounds in both athletic and sedentary populations.
中文翻译：
琥珀酸通过 SUNCR1 信号传导诱导骨骼肌纤维重塑。
骨骼肌纤维从快肌纤维向慢肌纤维的转变对于持续和强直收缩事件、维持能量稳态和缓解疲劳非常重要。耐力或有氧运动可有效诱导骨骼肌重塑，同时也会产生多种三羧酸 (TCA) 循环中间体，包括琥珀酸。然而，琥珀酸是否调节肌纤维类型转变仍不清楚。在这里，我们发现饮食中补充琥珀酸可以增加小鼠骨骼肌的耐力运动能力、肌球蛋白重链 I 表达、需氧酶活性、耗氧量和线粒体生物发生。相比之下，琥珀酸降低了乳酸脱氢酶活性、乳酸产量和肌球蛋白重链 IIb 表达。此外，通过使用磷脂酶Cβ拮抗剂、SUNCR1全局敲除或SUNCR1腓肠肌特异性敲除产生的药理学或遗传功能丧失模型，我们发现琥珀酸对骨骼肌纤维型重塑的影响是由SUNCR1及其介导的下游钙/NFAT 信号通路。总之，我们的结果表明琥珀酸通过 SUNCR1 信号通路诱导骨骼肌纤维的转变。这些发现表明，基于琥珀酸盐的化合物对运动人群和久坐人群都有潜在的有益用途。
更新日期：2020-01-02
中文翻译：
琥珀酸通过 SUNCR1 信号传导诱导骨骼肌纤维重塑。
骨骼肌纤维从快肌纤维向慢肌纤维的转变对于持续和强直收缩事件、维持能量稳态和缓解疲劳非常重要。耐力或有氧运动可有效诱导骨骼肌重塑，同时也会产生多种三羧酸 (TCA) 循环中间体，包括琥珀酸。然而，琥珀酸是否调节肌纤维类型转变仍不清楚。在这里，我们发现饮食中补充琥珀酸可以增加小鼠骨骼肌的耐力运动能力、肌球蛋白重链 I 表达、需氧酶活性、耗氧量和线粒体生物发生。相比之下，琥珀酸降低了乳酸脱氢酶活性、乳酸产量和肌球蛋白重链 IIb 表达。此外，通过使用磷脂酶Cβ拮抗剂、SUNCR1全局敲除或SUNCR1腓肠肌特异性敲除产生的药理学或遗传功能丧失模型，我们发现琥珀酸对骨骼肌纤维型重塑的影响是由SUNCR1及其介导的下游钙/NFAT 信号通路。总之，我们的结果表明琥珀酸通过 SUNCR1 信号通路诱导骨骼肌纤维的转变。这些发现表明，基于琥珀酸盐的化合物对运动人群和久坐人群都有潜在的有益用途。
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