ω-6 Polyunsaturated fatty acids (linoleic acid) activate both autophagy and antioxidation in a synergistic feedback loop via TOR-dependent and TOR-independent signaling pathways
Open Access
- 30 July 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 11 (7), 1-19
- https://doi.org/10.1038/s41419-020-02750-0
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.Keywords
Funding Information
- National Natural Science Foundation of China (31830103, 31830103, 31830103, 31830103, 31830103, 31830103)
- Agriculture Research System of China (CARS-47-11, CARS-47-11)
- Agriculture Research System of China
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