PUBLICATION

Prostaglandin 2α Promotes Autophagy and Mitochondrial Energy Production in Fish Hepatocytes

Authors
Tian, J., Du, Y., Yu, E., Lei, C., Xia, Y., Jiang, P., Li, H., Zhang, K., Li, Z., Gong, W., Xie, J., Wang, G.
ID
ZDB-PUB-220625-8
Date
2022
Source
Cells   11(12): (Journal)
Registered Authors
Keywords
ATP, PGF2α, arachidonic acid, cyclooxygenase, eicosanoids, lipid droplets, lipolysis, lipophagy, mitochondria
MeSH Terms
  • Animals
  • Autophagy
  • Dinoprost/metabolism
  • Hepatocytes/metabolism
  • Lipid Droplets*/metabolism
  • Prostaglandins/metabolism
  • Zebrafish*
PubMed
35740999 Full text @ Cells
Abstract
Fatty liver, characterized by excessive lipid droplet (LD) accumulation in hepatocytes, is a common physiological condition in humans and aquaculture species. Lipid mobilization is an important strategy for modulating the number and size of cellular LDs. Cyclooxygenase (COX)-mediated arachidonic acid derivatives are known to improve lipid catabolism in fish; however, the specific derivatives remain unknown. In the present study, we showed that serum starvation induced LD degradation via autophagy, lipolysis, and mitochondrial energy production in zebrafish hepatocytes, accompanied by activation of the COX pathway. The cellular concentration of PGF2α, but not other prostaglandins, was significantly increased. Administration of a COX inhibitor or interference with PGF2α synthase abolished serum deprivation-induced LD suppression, LD-lysosome colocalization, and expression of autophagic genes. Additionally, exogenous PGF2α suppressed the accumulation of LDs, promoted the accumulation of lysosomes with LD and the autophagy marker protein LC3A/B, and augmented the expression of autophagic genes. Moreover, PGF2α enhanced mitochondrial accumulation and ATP production, and increased the transcript levels of β-oxidation- and mitochondrial respiratory chain-related genes. Collectively, these findings demonstrate that the COX pathway is implicated in lipid degradation induced by energy deprivation, and that PGF2α is a key molecule triggering autophagy, lipolysis, and mitochondrial development in zebrafish hepatocytes.
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Human Disease / Model
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Mapping