Key Laboratory of Chemical Biology of Fujian Province, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
Research and Communication Center of Exercise and Health, Xiamen University of Technology, Xiamen 361021, China.
Molecules. 2021 Mar 25;26(7):1841. doi: 10.3390/molecules26071841.
α-Ketoglutarate (AKG) is attracting much attention from researchers owing to its beneficial effects on anti-aging and cancer suppression, and, more recently, in nutritional supplements. Given that glucose is the main source of energy to maintain normal physiological functions of skeletal muscle, the effects of AKG supplementation for improving muscle performance are closely related to the glucose level in skeletal muscle. The differences of AKG-induced effects in skeletal muscle between two states of normal energy and energy deficiency are unclear. Furthermore, AKG-induced metabolic changes in skeletal muscles in different energy states also remain elusive. Here, we assessed the effects of AKG supplementation on mouse C2C12 myoblast cells cultured both in normal medium (Nor cells) and in low-glucose medium (Low cells), which were used to mimic two states of normal energy and energy deficiency, respectively. We further performed NMR-based metabolomic analysis to address AKG-induced metabolic changes in Nor and Low cells. AKG supplementation significantly promoted the proliferation and differentiation of cells in the two energy states through glutamine metabolism, oxidative stress, and energy metabolism. Under normal culture conditions, AKG up-regulated the intracellular glutamine level, changed the cellular energy status, and maintained the antioxidant capacity of cells. Under low-glucose culture condition, AKG served as a metabolic substrate to reduce the glutamine-dependence of cells, remarkably enhanced the antioxidant capacity of cells and significantly elevated the intracellular ATP level, thereby ensuring the normal growth and metabolism of cells in the state of energy deficiency. Our results provide a mechanistic understanding of the effects of AKG supplements on myoblasts in both normal energy and energy deficiency states. This work may be beneficial to the exploitation of AKG applications in clinical treatments and nutritional supplementations.
α- 酮戊二酸（AKG）因其对抗衰老和抑制癌症的有益作用，以及最近在营养补充剂中的作用，引起了研究人员的广泛关注。由于葡萄糖是维持骨骼肌正常生理功能的主要能量来源，AKG 补充剂改善肌肉性能的作用与骨骼肌中的葡萄糖水平密切相关。AKG 补充剂在正常能量和能量缺乏两种状态下对骨骼肌的影响的差异尚不清楚。此外，不同能量状态下 AKG 诱导的骨骼肌代谢变化也不清楚。在这里，我们评估了 AKG 补充剂对正常培养基（Nor 细胞）和低糖培养基（Low 细胞）培养的 C2C12 成肌细胞的影响，分别模拟正常能量和能量缺乏两种状态。我们进一步进行了基于 NMR 的代谢组学分析，以研究 AKG 在 Nor 和 Low 细胞中诱导的代谢变化。AKG 补充剂通过谷氨酰胺代谢、氧化应激和能量代谢显著促进了两种能量状态下细胞的增殖和分化。在正常培养条件下，AKG 上调了细胞内谷氨酰胺水平，改变了细胞的能量状态，并维持了细胞的抗氧化能力。在低糖培养条件下，AKG 作为代谢底物降低了细胞对谷氨酰胺的依赖性，显著增强了细胞的抗氧化能力，显著提高了细胞内 ATP 水平，从而确保了能量缺乏状态下细胞的正常生长和代谢。我们的研究结果提供了 AKG 补充剂对正常能量和能量缺乏状态下成肌细胞影响的机制理解。这项工作可能有助于 AKG 在临床治疗和营养补充中的应用。
