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. 2024 Mar;1869(2):159428. doi: 10.1016/j.bbalip.2023.159428. Epub 2023 Nov 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • Animals
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Inflammasomes* / genetics
  • Mitophagy
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Palmitic Acid / pharmacology
  • Perciformes* / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NF-kappa B
  • Palmitic Acid
  • Reactive Oxygen Species
  • AMP-Activated Protein Kinases
  • Caspase 1