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

The rabbitfish Siganus canaliculatus is the first marine teleost found to have the biosynthetic ability of long-chain polyunsaturated fatty acids (LC-PUFA) from C-18 precursors catalyzed by fatty acyl desaturases (Delta 6/Delta 5 Fads, Delta 4 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 Delta 6/Delta 5 fads and Delta 4 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 Delta 6/Delta 5 fads core promoter, but not in Delta 4 fads promoter. Moreover, a unique stimulatory protein 1 (Sp1) element was predicted in the INS responding region of Delta 6/Delta 5 fads. Subsequently, SRE, NF-Y and Sp1 elements were proved as IREs in Delta 6/Delta 5 fads promoter. The up-regulation of INS on gene expression of Srebp-1c, Sp1, Delta 6/Delta 5 fads and elov15 as well as the LC-PUFA biosynthesis was further demonstrated in S. canaliculatus hepatocyte line (SCHL) cells, but no influence was detected on Delta 4 fads. Besides, inhibitors of transcription factors Srebp-1c (Fatostatin, PF-429242) and Sp1 (Mithramycin) could inhibit the gene expression of Srebp-1c, Delta 6/Delta 5 fads and elov15, and abolish the upregulation 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.

Automated summary

The study found that the rabbitfish is the first marine teleost with the ability to synthesize long-chain polyunsaturated fatty acids (LC-PUFA) from C-18 precursors through the regulation of insulin response elements (IREs) with the involvement of transcription factors Srebp-1c and Sp1.