Regulation of sirt1 and foxo1 in glucose metabolism of Megalobrama amblycephala

Both silent information regulator 2 homolog 1 (sirt1) and forkhead box transcription factor 1 (foxo1) are crucial transcription factors involved in glucolipid metabolism and energy regulation. Aim to understand their regulatory roles in glucose metabolism, this study first obtained the sequences of the sirt1 gene of Megalobrama amblycephala (masirt1) 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 Megalobrama amblycephala (M. amblycephala) using acute and long-term glucose tolerance assays. The results revealed that the full-length masirt1 cDNA sequence was 2350 bp and closely related to 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 and intestine of M. amblycephala exhibited synergistic 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, masirt1 is evolutionarily highly conserved, and the interaction site of sirt1and foxo1 is located in the nucleus. In long-term hyperglycemic regulation, sirt1 and foxo1 exhibit synergistic regulatory effects in the kidney and intestine of M. amblycephala. This study provides insights into how sirt1 and foxo1 regulate glucose metabolism in M. amblycephala.