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
Yang B, Zhou Y, Wu M, Li X, Mai K, Ai Q
Cell death & disease · 72 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- National Natural Science Foundation of China
- University or hospital
- Karolinska Institutet
- Government
- Agriculture Research System of China
- Government
- Recruitment Program of Global Experts
- Government
- National Science Fund for Distinguished Young Scholars
- Grants
- National Science Fund for Distinguished Young Scholars (31525024); National Natural Science Foundation of China (2018-29); Agriculture Research System of China (2018-29); National Natural Science Foundation of China (31830103); National Natural Science Foundation of China (CARS-47); Agriculture Research System of China (CARS‐47‐11); National Natural Science Foundation of China (31525024); Agriculture Research System of China (CARS47); National Natural Science Foundation of China (47-11)
Based on 5 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2020-07-30 · Cell Death Dis · vol. 11 · issue 7 · p. 607
- Publisher
- Springer Nature
- Cited
- 125 citations · more than 96% of similar papers · 4.1× the field average
- Impact
- Top 10% most cited in its field
- References
- 44 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Genomics, phytochemicals, and oxidative stress · Autophagy in Disease and Therapy · Alcohol Consumption and Health Effects
- Keywords
- Linoleic acid, Cell biology, Polyunsaturated fatty acid, Autophagy, Signal transduction, Chemistry, Biochemistry, TOR signaling, Biology, Fatty acid, Apoptosis
- MeSH
- hepatocytes, animals, perciformes, humans, adenylate kinase, linoleic acid, antioxidants, signal transduction, base sequence, protein binding, dietary supplements, autophagy, nf-e2-related factor 2, promoter regions, genetic, feedback, physiological, hek293 cells, tor serine-threonine kinases, sequestosome-1 protein, kelch-like ech-associated protein 1
6 authors
From CN
- Bo YangQingdao National Laboratory for Marine Science and Technology; Ministry of Agriculture and Rural Affairs; Ocean University of China
- Yan ZhouQingdao National Laboratory for Marine Science and Technology; Ministry of Agriculture and Rural Affairs; Ocean University of China
- Mengjiao WuQingdao National Laboratory for Marine Science and Technology; Ministry of Agriculture and Rural Affairs; Ocean University of China
- Xueshan LiQingdao National Laboratory for Marine Science and Technology; Ministry of Agriculture and Rural Affairs; Ocean University of China
- Kangsen MaiQingdao National Laboratory for Marine Science and Technology; Ministry of Agriculture and Rural Affairs; Ocean University of China
- Qinghui Ai · correspondingQingdao National Laboratory for Marine Science and Technology; Ocean University of China
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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