EPA but not DHA Prevents Lipid Metabolism Disorders by Regulating Myogenic IL-6 in High-fat fed mice

Qunying Xie; Lianzhi Mao; Ning Xiong; Qiting Cheng; Wei Tang; Ci Li; Chongxiang Zeng; Zhilin Liu; Limei Mao

doi:10.1016/j.jnutbio.2024.109815

EPA but not DHA Prevents Lipid Metabolism Disorders by Regulating Myogenic IL-6 in High-fat fed mice

J Nutr Biochem. 2024 Dec 9:109815. doi: 10.1016/j.jnutbio.2024.109815. Online ahead of print.

Authors

Qunying Xie¹, Lianzhi Mao¹, Ning Xiong¹, Qiting Cheng¹, Wei Tang¹, Ci Li¹, Chongxiang Zeng¹, Zhilin Liu¹, Limei Mao²

Affiliations

¹ Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, Guangdong, P. R. China.
² Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, Guangdong, P. R. China. Electronic address: mlm912@163.com.

PMID: 39662638
DOI: 10.1016/j.jnutbio.2024.109815

Abstract

Lipid metabolism disorder serve as a critical starting point for the development of chronic non-communicable diseases (NCDs). Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) are known for their lipid-lowering properties, but few studies have revealed their differences from the perspective of skeletal muscle endocrinology. Myogenic IL-6 has garnered significant attention for its role in energy distribution. The primary aim of this study was to investigate the effects and mechanisms of EPA and DHA on myogenic IL-6 and lipid metabolism disorders in mice, and to clarify the association between the alleviation of lipid metabolism disorders and myogenic IL-6 mediated by EPA/DHA. We found that EPA and DHA not only prevented high-fat diet-induced lipid metabolism disorders, but also up-regulated the expression of myogenic IL-6 by activating TRPV1/Ca²⁺ signaling in skeletal muscle. However, the lipid metabolism prevention effect mediated by EPA was weakened after knockout gene of myogenic IL-6, with its body weight and body fat increased and a large amounts of lipid deposited in the blood, liver, and adipocytes. Meanwhile, there no significantly differences of AMPK/STAT3 signaling in adipose tissue between groups after knockout gene of myogenic IL-6. Based on the results above, we concluded that EPA and DHA can stimulate the production of myogenic IL-6 through TRPV1/Ca²⁺ signaling in skeletal muscle. The prevention effect of lipid metabolism disorders by EPA, but not DHA, relies on myogenic IL-6, with the underlying mechanism may involving the enhancement of AMPK/STAT3 signaling mediated by myogenic IL-6 in adipose tissues.

Keywords: AMPK/STAT3; DHA; EPA; Lipid metabolism; Myogenic IL-6; TRPV1/Ca(2+).