Amino acids attenuate insulin action on gluconeogenesis and promote fatty acid biosynthesis via mTORC1 signaling pathway in trout hepatocytes - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cellular Physiology and Biochemistry Année : 2015

Amino acids attenuate insulin action on gluconeogenesis and promote fatty acid biosynthesis via mTORC1 signaling pathway in trout hepatocytes

Résumé

Background/Aims: Carnivores exhibit poor utilization of dietary carbohydrates and glucose intolerant phenotypes, yet it remains unclear what are the causal factors and underlying mechanisms. We aimed to evaluate excessive amino acids (AAs)-induced effects on insulin signaling, fatty acid biosynthesis and glucose metabolism in rainbow trout and determine the potential involvement of mTORC1 and p38 MAPK pathway. Methods: We stimulated trout primary hepatocytes with different AA levels and employed acute administration of rapamycin to inhibit mTORC1 activation. Results: Increased AA levels enhanced the phosphorylation of ribosomal protein S6 kinase (S6K1), S6, and insulin receptor substrate 1 (IRS-1) on Ser302 but suppressed Akt and p38 phosphorylation; up-regulated the expression of genes related to gluconeogenesis and fatty acid biosynthesis. mTORC1 inhibition not only inhibited the phosphorylation of mTORC1 downstream targets, but also blunted IRS-1 Ser302 phosphorylation and restored excessive AAs-suppressed Akt phosphorylation. Rapamycin also inhibited fatty acid biosynthetic and gluconeogenic gene expression. Conclusion: High levels of AAs upregulate hepatic fatty acid biosynthetic gene expression through an mTORC1-dependent manner, while attenuate insulin-mediated repression of gluconeogenesis through elevating IRS-1 Ser302 phosphorylation, which in turn impairs Akt activation and thereby weakening insulin action. We propose that p38 MAPK probably also involves in these AAs-induced metabolic changes
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Dates et versions

hal-01901412 , version 1 (27-05-2020)

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Wei Wei Dai, Stéphane Panserat, Elisabeth Plagnes Juan, Iban Seiliez, Sandrine Skiba-Cassy. Amino acids attenuate insulin action on gluconeogenesis and promote fatty acid biosynthesis via mTORC1 signaling pathway in trout hepatocytes. Cellular Physiology and Biochemistry, 2015, 36 (3), pp.1084-1100. ⟨10.1159/000430281⟩. ⟨hal-01901412⟩
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