Transcriptomic profiling reveals coordinated hepatic metabolic reprogramming involving gluconeogenesis and fatty acid β-oxidation during cold exposure in Xenopus laevis

Background Ectothermic vertebrates exhibit substantial physiological plasticity in response to environmental temperature fluctuations. Among them, amphibians show particularly pronounced metabolic adjustments under cold conditions; however, the molecular mechanisms underlying hepatic response to low temperatures remain poorly understood. To address this gap, we investigated the hepatic transcriptional response to cold exposure in the African clawed frog ( Xenopus laevis ) using RNA sequencing (RNA-seq) and quantitative PCR. Results Exposure to 5 °C for five days in X. laevis resulted in pronounced hyperglycemia and extensive transcriptional reprogramming in the liver. RNA-seq analysis indicated that, relative to frogs maintained at 24 °C, 2,392 genes were upregulated, whereas 2,031 genes were downregulated. Notably, genes associated with gluconeogenesis, such as foxo1 , g6pc1 , and pck1 , exhibited significant upregulation, whereas genes related to glycolysis and glucose utilization, including gck , pfkm , and ldhb , were downregulated. Concurrently, genes involved in fatty acid biosynthesis, fatty acid desaturation, and cholesterol biosynthesis, including srebf1 , acaca , fasn , scd , fads2 , srebf2 , and hmgcr , were upregulated. Conversely, genes related to fatty acid β-oxidation, including ppara , cpt1a , cpt1b , slc25a20 , acadl , hadha , and hadhb , were significantly downregulated. In alignment with this pattern, multiple genes encoding components of the mitochondrial electron transport chain and ATP synthesis machinery were also downregulated. Additionally, gene groups involved in antioxidant defenses, such as gpx4 , gpx1 , prdx2 , prdx5 , prdx6 , and ferritin-related genes, were upregulated. Representative transcriptomic changes were validated using quantitative PCR analysis. Conclusions Exposure to cold temperatures induced hyperglycemia and coordinated transcriptional metabolic reprogramming in the liver of X. laevis . The observed transcriptional changes were characterized by upregulation of genes associated with gluconeogenesis and lipid and cholesterol biosynthesis, together with downregulation of genes associated with glycolysis, fatty acid β-oxidation, and oxidative phosphorylation. These coordinated transcriptional changes are consistent with a hepatic response that may support glucose homeostasis and energy conservation during cold exposure. Our findings provide a transcriptional framework for understanding hepatic responses to cold exposure in X. laevis and identify key metabolic pathways for future functional investigation.