2. Academic Validation
  3. Palmitic acid activates NLRP3 inflammasome through NF-κB and AMPK-mitophagy-ROS pathways to induce IL-1β production in large yellow croaker (Larimichthys crocea)

Palmitic acid activates NLRP3 inflammasome through NF-κB and AMPK-mitophagy-ROS pathways to induce IL-1β production in large yellow croaker (Larimichthys crocea)

  • Biochim Biophys Acta Mol Cell Biol Lipids. 2023 Nov 27:159428. doi: 10.1016/j.bbalip.2023.159428.
Xueshan Li 1,  Kangsen Mai 2,  Qinghui Ai 3
Affiliations

Affiliations

  • 1 Key laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture and Rural Affairs, Ocean University of China, 5 Yushan Road, Qingdao, Shandong 266003, People's Republic of China; The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao, Shandong 266003, People's Republic of China.
  • 2 Key laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture and Rural Affairs, Ocean University of China, 5 Yushan Road, Qingdao, Shandong 266003, People's Republic of China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, Qingdao, Shandong 266237, People's Republic of China; The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao, Shandong 266003, People's Republic of China.
  • 3 Key laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture and Rural Affairs, Ocean University of China, 5 Yushan Road, Qingdao, Shandong 266003, People's Republic of China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, Qingdao, Shandong 266237, People's Republic of China; The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao, Shandong 266003, People's Republic of China. Electronic address: qhai@ouc.edu.cn.
PMID: 38029958 DOI: 10.1016/j.bbalip.2023.159428
Abstract

Studies on marine fish showed that vegetable oils substituted for excessive fish oil increased interleukin-1β (IL-1β) production. However, whether the nucleotide-binding oligomerization domain, leucine-rich repeat-containing family, pyrin domain-containing-3 (NLRP3) inflammasome has a substantial role in fatty acid-induced IL-1β production in fish remains unclear. The associated specific mechanism is also unknown. In this study, NLRP3, Caspase-1 and apoptosis-associated speck-like protein containing a CARD (asc) were successfully cloned, and NLRP3 inflammasome consisted of NLRP3, Caspase-1 and ASC in large yellow croaker. Primary hepatocytes of fish incubated with palmitic acid (PA) exhibited the highest expression of pro-inflammatory genes (il-1β and tnfα) and NLRP3 inflammasome related genes (NLRP3, Caspase-1 and asc), Caspase-1 activity and IL-1β production among different treatments. Furthermore, PA-induced NLRP3 inflammasome activation was confirmed to require two signals: the first signal was that PA promoted the NF-κB (P65) protein into the nucleus, and NF-κB increased NLRP3 promoter activity and NLRP3 transcription. The second signal was that PA inhibited AMPK phosphorylation and decreased Mitophagy by inhibiting the expression of PINK and parkin proteins, thereby damaging the mitochondria that could not be effectively cleared. Mitochondrial damage generated excessive amounts of Reactive Oxygen Species, which activated the NLRP3 inflammasome and then induced Caspase-1 activity and IL-1β production. Therefore, excessive dietary PA activated NLRP3 inflammasome through NF-κB and AMPK-mitophagy-ROS pathways to induce IL-1β production, thereby leading to inflammation in fish.

Keywords

IL-1β; Inflammatory response; Large yellow croaker; NLRP3 inflammasome; Palmitic acid.

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