Oxaloacetic acid induces muscle energy substrate depletion and fatigue by JNK-mediated mitochondrial uncoupling.

Autor: Yin C; Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, Key Laboratory of State Ethnic Affairs Commission for Biological Technology, College of Life Science, South-Central Minzu University, Wuhan, China.; Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, Guangdong Province Key Laboratory of Animal Nutritional Regulation, College of Animal Science, South China Agricultural University, Guangzhou, China., Qin R; Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, Key Laboratory of State Ethnic Affairs Commission for Biological Technology, College of Life Science, South-Central Minzu University, Wuhan, China., Ma Z; Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, Guangdong Province Key Laboratory of Animal Nutritional Regulation, College of Animal Science, South China Agricultural University, Guangzhou, China., Li F; Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, Guangdong Province Key Laboratory of Animal Nutritional Regulation, College of Animal Science, South China Agricultural University, Guangzhou, China., Liu J; Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, Key Laboratory of State Ethnic Affairs Commission for Biological Technology, College of Life Science, South-Central Minzu University, Wuhan, China., Liu H; Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, Key Laboratory of State Ethnic Affairs Commission for Biological Technology, College of Life Science, South-Central Minzu University, Wuhan, China., Shu G; Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, Guangdong Province Key Laboratory of Animal Nutritional Regulation, College of Animal Science, South China Agricultural University, Guangzhou, China., Xiong H; Hubei Provincial Key Laboratory for Protection and Application of Special Plant Germplasm in Wuling Area of China, Key Laboratory of State Ethnic Affairs Commission for Biological Technology, College of Life Science, South-Central Minzu University, Wuhan, China., Jiang Q; Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, Guangdong Province Key Laboratory of Animal Nutritional Regulation, College of Animal Science, South China Agricultural University, Guangzhou, China.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Feb; Vol. 38 (2), pp. e23373.
DOI: 10.1096/fj.202301796R
Abstrakt: Fatigue is a common phenomenon closely related to physical discomfort and numerous diseases, which is severely threatening the life quality and health of people. However, the exact mechanisms underlying fatigue are not fully characterized. Herein, we demonstrate that oxaloacetic acid (OAA), a crucial tricarboxylic acid cycle intermediate, modulates the muscle fatigue. The results showed that serum OAA level was positively correlated with fatigue state of mice. OAA-treated induced muscle fatigue impaired the exercise performance of mice. Mechanistically, OAA increased the c-Jun N-terminal kinase (JNK) phosphorylation and uncoupling protein 2 (UCP2) levels in skeletal muscle, which led to decreased energy substrate and enhanced glycolysis. On the other hand, OAA boosted muscle mitochondrial oxidative phosphorylation uncoupled with energy production. In addition, either UCP2 knockout or JNK inhibition totally reversed the effects of OAA on skeletal muscle. Therein, JNK mediated UCP2 activation with OAA-treated. Our studies reveal a novel role of OAA in skeletal muscle metabolism, which would shed light on the mechanism of muscle fatigue and weakness.
(© 2024 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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