Cold-induced hepatic metabolic change links gluconeogenesis, lipid remodeling, and redox regulation in Xenopus laevis

Cold environments pose substantial metabolic challenges to ectothermic organisms. In amphibians, such as the African clawed frog (Xenopus laevis), exposure to cold temperatures induces pronounced hyperglycemia; however, the molecular mechanisms underlying this response remain unclear. This study investigated the metabolic responses of the liver to cold exposure using transcriptome analysis. Adult frogs were subjected to a temperature of 5{degrees}C for five days, and their liver transcriptome was subsequently analyzed using RNA sequencing. Cold exposure significantly elevated blood glucose levels. Transcriptome analysis revealed extensive alterations in gene expression, including the upregulation of key gluconeogenesis-related genes. Notably, genes involved in FOXO1 signaling exhibited coordinated changes, with increased expression of foxo1 and its regulator prmt1 (arginine methyltransferase) and decreased expression of mdm2 (E3 ubiquitin ligase), suggesting that the phosphorylation of FOXO1 may be suppressed. Consistent with these findings, the expression of gluconeogenic genes (g6pc1 and pck1) was elevated, whereas the glycolytic gene gck was downregulated, indicating a shift towards glucose production. In addition to carbohydrate metabolism, genes involved in lipid and cholesterol metabolism, particularly fatty acid desaturases (scd and fads2), were also upregulated, suggesting that the remodeling of membrane lipid composition may occur under cold conditions. Furthermore, genes related to antioxidant and redox pathways, including those involved in the detoxification of reactive oxygen species and iron sequestration, were induced, indicating enhanced redox regulation. Collectively, these results demonstrate that cold exposure induces coordinated metabolic remodeling in the liver of X. laevis, characterized by enhanced gluconeogenesis, lipid remodeling, and robust redox regulation. SUMMARY STATEMENTCold exposure drives coordinated hepatic metabolic reprogramming in Xenopus laevis, elevating gluconeogenesis, modifying lipid composition, and strengthening antioxidant defenses through integrated transcriptional responses that support survival under a low-temperature environment.