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  2. Excessive linoleic acid induces muscle oxidative stress through 5-lipoxygenase-dependent peroxidation

Excessive linoleic acid induces muscle oxidative stress through 5-lipoxygenase-dependent peroxidation

  • Redox Biol. 2024 Feb 19:71:103096. doi: 10.1016/j.redox.2024.103096.
Xiufei Cao 1 Huixing Guo 1 Yongjun Dai 1 Guangzhen Jiang 2 Wenbin Liu 3 Xiangfei Li 1 Dingdong Zhang 1 Yangyang Huang 1 Xi Wang 1 Haokun Hua 1 Jianfeng Wang 1 Keke Chen 1 Cheng Chi 1 Hengtong Liu 1
Affiliations

Affiliations

  • 1 Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, National Experimental Teaching Center for Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, No.1 Weigang Road, 210095, Nanjing, Jiangsu, People's Republic of China.
  • 2 Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, National Experimental Teaching Center for Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, No.1 Weigang Road, 210095, Nanjing, Jiangsu, People's Republic of China. Electronic address: jianggz@njau.edu.cn.
  • 3 Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, National Experimental Teaching Center for Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, No.1 Weigang Road, 210095, Nanjing, Jiangsu, People's Republic of China. Electronic address: wbliu@njau.edu.cn.
Abstract

Oxidative stress in muscles is closely related to the occurrence of Insulin resistance, muscle weakness and atrophy, age-related sarcopenia, and Cancer. Aldehydes, a primary oxidation intermediate of polyunsaturated fatty acids, have been proven to be an important trigger for oxidative stress. However, the potential role of linoleic acid (LA) as a donor for volatile aldehydes to trigger oxidative stress has not been reported. Here, we reported that excessive dietary LA caused muscle redox imbalance and volatile aldehydes containing hexanal, 2-hexenal, and nonanal were the main metabolites leading to oxidative stress. Importantly, we identified 5-lipoxygenase (5-LOX) as a key Enzyme mediating LA peroxidation in crustaceans for the first time. The inhibition of 5-LOX significantly suppressed the content of aldehydes produced by excessive LA. Mechanistically, the activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway facilitated the translocation of 5-LOX from the nucleus to the cytoplasm, where 5-LOX oxidized LA, leading to oxidative stress through the generation of aldehydes. This study suggests that 5-LOX is a potential target to prevent the production of harmful aldehydes.

Keywords

5-Lipoxygenase; Crab muscle; Linoleic acid; Oxidative stress; Volatile aldehydes; cAMP/PKA signaling pathway.

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