HSF1-SELENOS pathway mediated dietary inorganic Se-induced lipogenesis via the up-regulation of PPARγ expression in yellow catfish

At present, studies involved in the effects of dietary Se sources on lipid metabolism were very scarce and the underlying mechanism remains unknown. Previous studies reported that dietary Se sources differentially affected selenoprotein S (SELENOS) expression and SELENOS affected lipid metabolism via the inositol-requiring enzyme 1 alpha (IRE1 alpha)-spliced X-box binding protein 1 (XBP1s) pathway. Thus, we used yellow catfish as an experimental model to explore whether dietary selenium sources affected the hepatic lipid metabolism, and further determined the role of SELENOS-IRE1 alpha-XBP1s pathway in dietary selenium sources affecting hepatic lipid metabolism. Compared with the selenomethionine (S-M) group, sodium selenite (S-S) group possessed higher liver tri-glycerides (TGs) (34.7%), lipogenic enzyme activities (57.9-70.6%), and lower antioxidant enzyme activities (23.3-35.5%), increased protein levels of heat shock transcription factor 1 (HSF1) and SELENOS (1.17-fold and 47.4%, respectively), and XBP1s-peroxisome proliferators-activated receptor gamma (PPAR gamma) pathway. Blocking SELENOS and PPAR gamma by RNA interference demonstrated that the SELENOS/XBP1s/PPAR gamma axis was critical for S-S-induced lipid accumulation. Moreover, S-S-induced upregulation of SELENOS was via the increased DNA binding capacity of HSF1 to SELENOS promoter, which activated the XBP1s/PPAR gamma pathway and promoted lipogenesis and lipid accumulation. XBP1s is required for S-S-induced upregulation of PPAR gamma expression. Our finding elucidated the mechanism of dietary Se sources affecting the lipid metabolism in the liver of yellow catfish and demonstrated novel function of SELENOS in metabolic regulation. Our study also suggested that seleno-methionine was a better Se source than selenite against abnormal lipid deposition in the liver of yellow catfish.

Automated summary

Currently, there is limited research on the effects of dietary selenium sources on lipid metabolism. This study investigated the impact of selenium sources on lipid metabolism in the liver of yellow catfish and identified the role of the SELENOS-IRE1 alpha-XBP1s pathway. The results showed that sodium selenite had a significant effect on lipid accumulation and regulation of lipogenic enzymes, while selenomethionine was a better source for preventing abnormal lipid deposition in the liver.