Novel insights for PI3KC3 in mediating lipid accumulation in yellow catfish Pelteobagrus fulvidraco

In this study, the transcriptional regulation of PI3KC3 by three transcription factors (PPAR gamma, PPAR alpha, and STAT3) and the potential role of PI3KC3 in mediating lipid accumulation were determined in yellow catfish Pelteobagrus fulvidraco. The 5'-deletion assay, overexpression assay, site-mutation assay, and electrophoretic mobility shift assay suggested that PPAR alpha, PPAR gamma, and STAT3 negatively regulated the promoter activity of pi3kc3. Moreover, the transcriptional inactivation of pi3kc3 was directly mediated by PPAR alpha and PPAR gamma under fatty acid (FA) treatment. Using primary hepatocytes from yellow catfish, FA incubation significantly increased triacylglyceride (TG) content, non-esterified fatty acid (NEFA) content, and lipid drops (LDs) content, the mRNA level of ppar alpha, ppar gamma, stat3, and dnmt3b, the protein level of PPAR alpha, PPAR gamma, and STAT3, and the methylation level of pi3kc3, but significantly reduced the mRNA and protein level of PI3KC3. Our findings offer new insights into the mechanisms for transcriptional regulation of PI3KC3 and for PI3KC3-mediated lipid accumulation in fish.

Automated summary

This study determined the transcriptional regulation of PI3KC3 by three transcription factors (PPAR gamma, PPAR alpha, and STAT3) and the potential role of PI3KC3 in mediating lipid accumulation in yellow catfish Pelteobagrus fulvidraco. The findings suggest that PPAR alpha and PPAR gamma directly regulate the transcription inactivation of pi3kc3, and fatty acid treatment significantly affects the expression and methylation level of PI3KC3 in yellow catfish hepatocytes.