Journal
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY
Volume 260, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cbpb.2022.110734
Keywords
Insulin; LC-PUFA biosynthesis; PI3K signal pathway; Srebp1; Rabbitfish Siganus canaliculatus
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Funding
- National Natural Science Foundation of China [31873040]
- National Key R&D Program of China [2018YFD0900400]
- Natural Science Foundation of Guangdong Province [2020A1515011252]
- Guangdong Provincial Key RD Programme [2021B0202050001]
- Innovation and Strong School Projects in Guangdong Province [2020ZDZXlO14]
- Shantou University (STU) Scientific Research Foundation for Talents Grant [NTF19019]
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This study showed that insulin could activate the biosynthesis of LC-PUFA in rabbitfish hepatocytes through the PI3K/Akt/mTOR/Srebp1 pathway, indicating a potentially important regulatory mechanism for lipid metabolism in fish.
Insulin is well known an important metabolic regulator in glucose and lipid metabolism. It has been proved to activate long-chain (> C-20) polyunsaturated fatty acids (LC-PUFA) biosynthesis in mammals, but little is known about such a role in fish. To explore the effects and molecular mechanisms of insulin in fish LC-PUFA biosynthesis, we treated the rabbitfish S. canaliculatus hepatocyte line (SCHL) cells with 65 nM insulin for 12 h, and the results showed that the mRNA levels of genes encoding the key enzymes and transcription factor involved in rabbitfish LC-PUFA biosynthesis such as delta 6 delta 5 fads2, elovl5 and srebp1, as well as those of PI3K pathway genes including pdk1, akt2 and mtor increased significantly. Moreover, SCHL cells treated with different PI3K/Akt pathway inhibitors (LY294002, Wortmannin, AKTi-1/2) alone or combined with insulin decreased the mRNA levels of PI3K/Akt/mTOR downstream signaling genes, including A6A5 fads2, A4 fads2, elovl5, elovl4 and srebp1. While PI3K/Akt agonists (740 Y-P, IGF-1, SC-79) had the opposite results. The results of fatty acid composition analysis of hepatocytes showed that insulin stimulation increased the A6A5 Fads2-dependent PUFA desaturation indexes, while Elovl5-dependent PUFA elongation indexes had upward trends, and consequently LC-PUFA contents increased. Taken together, these results indicated that insulin activated LC-PUFA biosynthesis probably through PI3K/Akt/mTOR/Srebp1 pathway in S. canaliculatus hepatocytes.
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