Abstract
ω-6 Polyunsaturated fatty acids (PUFAs) are essential fatty acids that participate in macroautophagy (hereafter referred to as autophagy) and the Kelch ECH-associating protein 1 (Keap1)—nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant system in organisms. However, the molecular mechanisms by which ω-6 PUFAs (linoleic acid) regulate autophagy and Keap1–Nrf2 antioxidant system are not completely understood. Therefore, the purposes of this study were to explore the molecular mechanisms by which ω-6 PUFAs (linoleic acid) regulate autophagy and antioxidant system and to investigate the potential relationship between autophagy and antioxidant system through transcriptomic analysis, quantitative real-time polymerase chain reaction (RT-qPCR), western blot analysis, coimmunoprecipitation (Co-IP) and electrophoretic mobility shift assays (EMSAs) in vivo and in vitro. The results of the present study indicated that ω-6 PUFAs in diets induced autophagy but decrease antioxidant ability in vivo. However, the results also provided evidence, for the first time, that ω-6 PUFAs (linoleic acid) induced autophagy and increased antioxidant ability through the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway and the AMPK-target of rapamycin (TOR) signaling pathway in hepatocytes in vitro. Interestingly, the findings revealed a ω-6 PUFA-induced synergistic feedback loop between autophagy and antioxidant system, which are connected with each other through the P62 and Keap1 complex. These results suggested that ω-6 PUFAs (linoleic acid) could be useful for activating a synergistic feedback loop between autophagy and antioxidant system and could greatly aid in the prevention and treatment of multiple pathologies.
Highlights
Introduction ω6 Polyunsaturated fatty acids (PUFAs) are essential fatty acids that participate in multiple types of cellular metabolism[1]
To identify the active biological pathways in large yellow croaker, 1237 differentially expressed genes were mapped to canonical signaling pathways found in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database (Supplementary Fig. 1C)
On the basis of the transcriptomic evidence, we examined the effects of ω-6 PUFAs on autophagy and antioxidation
Summary
6 Polyunsaturated fatty acids (PUFAs) are essential fatty acids that participate in multiple types of cellular metabolism[1]. A considerable number of studies have demonstrated the antistress activity mediated by ω-6. Key Laboratory of Aquaculture Nutrition and Feed Rural Affairs) & Key Laboratory of Mariculture (Ministry of Education), Ocean. University of China, 5 Yushan Road, 266003 Qingdao, Shandong, People’s. 266237 Qingdao, Shandong, People’s Republic of China. PUFAs, including alleviation of oxidative stress, modulation of cyclooxygenase activity and changes in membrane phospholipid composition and receptor function[2,3,4,5]. The stress-preventive mechanisms mobilized by ω-6 PUFAs are not completely understood. Two such host defense mechanisms, autophagy and
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