Insulin can up-regulate LC-PUFA biosynthesis with the involvement of Srebp-1c and stimulatory protein 1 (Sp1) in marine teleost Siganus canaliculatus

by Selleckchem | May 07 2023

The rabbitfish Siganus canaliculatus is the first marine teleost found to have the biosynthetic ability of long-chain polyunsaturated fatty acids (LC-PUFA) from C18 precursors catalyzed by fatty acyl desaturases (Δ6/Δ5 Fads, Δ4 Fads) and elongases of very long chain fatty acids (Elovls). Previously, we predicted the existence of insulin (INS) response elements (IREs) including nuclear factor Y (NF-Y) and sterol regulatory element (SRE) in the core promoter region of rabbitfish Δ6/Δ5 fads and Δ4 fads. To clarify the potential regulatory effect and mechanism of INS in LC-PUFA biosynthesis, INS responding region was identified at -456 bp to + 51 bp of Δ6/Δ5 fads core promoter, but not in Δ4 fads promoter. Moreover, a unique stimulatory protein 1 (Sp1) element was predicted in the INS responding region of Δ6/Δ5 fads. Subsequently, SRE, NF-Y and Sp1 elements were proved as IREs in Δ6/Δ5 fads promoter. The up-regulation of INS on gene expression of Srebp-1c, Sp1, Δ6/Δ5 fads and elovl5 as well as the LC-PUFA biosynthesis was further demonstrated in S. canaliculatus hepatocyte line (SCHL) cells, but no influence was detected on Δ4 fads. Besides, inhibitors of transcription factors Srebp-1c (Fatostatin, PF-429242) and Sp1 (Mithramycin) could inhibit the gene expression of Srebp-1c, Δ6/Δ5 fads and elovl5, and abolish the up-regulation of INS on these genes' expression and LC-PUFA biosynthesis. These results indicated that INS could up-regulate LC-PUFA biosynthesis with the involvement of Srebp-1c and Sp1 in rabbitfish S. canaliculatus, which is the first report in teleost.

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The above passage describes a study on the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFA) in the marine teleost Siganus canaliculatus (rabbitfish). The study identified insulin response elements (IREs) in the core promoter region of the Δ6/Δ5 fads and Δ4 fads genes involved in LC-PUFA biosynthesis, and demonstrated that insulin (INS) could up-regulate LC-PUFA biosynthesis in rabbitfish through the involvement of transcription factors Srebp-1c and Sp1.

The study used a hepatocyte cell line derived from rabbitfish (SCHL cells) to investigate the effects of INS on LC-PUFA biosynthesis and gene expression. The researchers found that INS up-regulated the expression of Srebp-1c, Sp1, Δ6/Δ5 fads, and elovl5 genes, as well as LC-PUFA biosynthesis in SCHL cells, but had no effect on Δ4 fads gene expression.

Furthermore, the study showed that inhibitors of transcription factors Srebp-1c and Sp1 could inhibit the up-regulation of INS on gene expression of Srebp-1c, Δ6/Δ5 fads, and elovl5, and abolish the up-regulation of INS on LC-PUFA biosynthesis.

Overall, the study provides insight into the regulatory mechanism of LC-PUFA biosynthesis in rabbitfish and highlights the potential role of INS and transcription factors Srebp-1c and Sp1 in this process.