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. This study explored the molecular mechanisms by which ω-6 PUFAs (linoleic acid) regulate autophagy and the antioxidant system. In vivo, ω-6 PUFAs induced autophagy but decreased antioxidant ability. In vitro, 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. A ω-6 PUFA-induced synergistic feedback loop between autophagy and the antioxidant system was revealed, connected through the P62 and Keap1 complex. These results suggest ω-6 PUFAs (linoleic acid) could be useful for activating this feedback loop and aiding in the prevention and treatment of multiple pathologies.

Bo Yang, Yan Zhou, Mengjiao Wu, Xueshan Li, Kangsen Mai, Qinghui Ai