Regulation of Sirt1 and Foxo1 in Glucose Metabolism of Megalobrama Amblycephala

Abstract

Both Sirt1 and Foxo1 are crucial transcription factors involved in glucolipid metabolism and energy regulation. To understand their regulatory roles in the glucose metabolism of freshwater fish, this study first obtained the sequences of the Masirt1 gene through molecular cloning and sequencing. We then analyzed the localization of the cellular interaction of both factors and further investigated their effects and action patterns in the glucose metabolism of M. amblycephala using acute and long-term glucose tolerance assays. The results revealed that the full-length masirt1 cDNA sequence was 2350 bp and was closely related to that of Sinocyclocheilus rhinocerous. Sirt1 and foxo1 were found to be mutually dependent and localized in the nucleus. Acute glucose tolerance tests revealed that the expression levels of both factors in the liver of M. amblycephala showed an initial increase followed by a decrease. Blood glucose levels in M. amblycephala significantly increased at 2 and 12 h (P < 0.05). In a long-term breeding experiment with high-sugar feeding, the expression of the sirt1 and foxo1 genes in the kidney, liver, and intestine of M. amblycephala exhibited coordinated changes. The 51WS groups had significantly higher levels of sirt1 and foxo1 gene expression in the kidney and intestine compared to the 0WS and 17WS groups (P < 0.05). Overall, sirt1 and foxo1 are highly evolutionarily conserved, with their interaction site located in the nucleus. In short-term and long-term hyperglycemic regulation, sirt1 and foxo1 exhibit synergistic regulatory effects in the liver, kidney, and intestine of M. amblycephala, respectively.

Keywords: Megalobrama amblycephala, sirt1, foxo1, Glucose metabolism, interaction