Cao Wei, Liu Yajin, Wei Hao, Dong Yunfeng, Sun Haipeng, Zhang Xuejiao, Qiu Junqiang
Department of Exercise Biochemistry, Exercise Science School, Beijing Sport University, Beijing, China.
College of Sports and Health, Shandong Sport University, Rizhao, China.
Front Nutr. 2024 Nov 20;11:1451429. doi: 10.3389/fnut.2024.1451429. eCollection 2024.
Emerging evidences suggests that the disrupted branched-chain amino acids (BCAAs) homeostasis and elevated BCAAs promote obesity-related insulin resistance (IR). Exercise improves insulin sensitivity. However, whether BCAAs plays a role in the exercise-attenuated IR remains to be fully investigated.
In this study, male C57BL/6J mice were induced to become diet-induced obese (DIO) and served as subjects. The initial investigation focused on the impact of exercise on IR and BCAAs. The DIO mice were randomly assigned to either a sedentary group (CON, = 16) or an exercise group (EX, = 16). The EX group underwent a 12-week aerobic exercise regimen on a treadmill. After 12-week, plasma BCAAs and branched-chain keto acids (BCKAs) were measured by liquid chromatography-mass spectrometry, glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed, and the expression and phosphorylation of BCAAs catabolic proteins, as well as AKT T308 in gastrocnemius muscle and liver tissues, were evaluated using western blotting. Subsequently, the study explored the role of BCAAs in enhancing IR through exercise. Mice were randomly allocated into 4 groups: sedentary group (CON, = 8), sedentary with BCAAs supplementation group (CON+BCAA, = 8), exercise group (EX, = 16), and exercise with BCAAs supplementation group (EX+BCAA, = 16). The exercise protocol was as above. Mice in the BCAAs supplemented groups received drinking water containing 2% BCAAs. After 12-week, plasma BCAAs and BCKAs were measured, GTT and ITT tests were performed, and the phosphorylation of AKT T308, as well as p70S6K T389 in gastrocnemius muscle and liver, were compared between the EX group and the EX+BCAA group. Additionally, the phosphorylation of AMPKα T172 in both tissues was measured across all four groups.
12-week aerobic exercise improved insulin sensitivity in DIO mice while inducing BCAAs catabolic protein expression in skeletal muscle and liver, and reducing the plasma BCAAs level. Importantly, BCAAs supplementation elevated the plasma level of BCAAs and counteracted the exercise-attenuated IR. In skeletal muscle and liver tissues, BCAAs supplementation impaired the exercise-improved insulin signaling without enhancing mammalian target of rapamycin activity. AMPK activity was enhanced by aerobic exercise, which was abolished by BCAAs supplementation.
Aerobic exercise attenuated insulin resistance via restoring BCAAs homeostasis and AMPK activity. The impacts of BCAAs intake on the metabolic effects of exercise sheds light on the combined exercise and nutrition intervention strategy for diabetes management.
新出现的证据表明，支链氨基酸（BCAAs）稳态破坏以及BCAAs水平升高会促进肥胖相关的胰岛素抵抗（IR）。运动可改善胰岛素敏感性。然而，BCAAs在运动减轻的IR中是否起作用仍有待充分研究。
在本研究中，雄性C57BL/6J小鼠被诱导成为饮食诱导肥胖（DIO）小鼠并作为研究对象。初步研究聚焦于运动对IR和BCAAs的影响。DIO小鼠被随机分为久坐组（CON，n = 16）或运动组（EX，n = 16）。EX组在跑步机上进行为期12周的有氧运动方案。12周后，通过液相色谱 - 质谱法测量血浆BCAAs和支链酮酸（BCKAs），进行葡萄糖耐量试验（GTT）和胰岛素耐量试验（ITT），并使用蛋白质免疫印迹法评估BCAAs分解代谢蛋白以及腓肠肌和肝脏组织中AKT T308的表达和磷酸化。随后，该研究探讨了BCAAs在通过运动增强IR中的作用。小鼠被随机分为4组：久坐组（CON，n = 8）、补充BCAAs的久坐组（CON + BCAA，n = 8）、运动组（EX，n = 16）和补充BCAAs的运动组（EX + BCAA，n = 16）。运动方案如上所述。补充BCAAs组的小鼠饮用含2% BCAAs的水。12周后，测量血浆BCAAs和BCKAs，进行GTT和ITT试验，并比较EX组和EX + BCAA组腓肠肌和肝脏中AKT T308以及p70S6K T389的磷酸化情况。此外，测量所有四组中两个组织中AMPKα T172的磷酸化情况。
12周的有氧运动改善了DIO小鼠的胰岛素敏感性，同时诱导了骨骼肌和肝脏中BCAAs分解代谢蛋白的表达，并降低了血浆BCAAs水平。重要的是，补充BCAAs提高了血浆BCAAs水平，并抵消了运动减轻的IR。在骨骼肌和肝脏组织中，补充BCAAs损害了运动改善的胰岛素信号传导，而未增强雷帕霉素靶蛋白活性。有氧运动增强了AMPK活性，而补充BCAAs则消除了这种增强作用。
有氧运动通过恢复BCAAs稳态和AMPK活性减轻胰岛素抵抗。BCAAs摄入对运动代谢效应的影响为糖尿病管理的运动与营养联合干预策略提供了思路。
