NAD⁺ /sirtuin metabolism is enhanced in response to cold-induced changes in lipid metabolism in mouse liver

The nicotinamide adenine dinucleotide (NAD⁺ )/Sirtuin (SIRT) system is linked to metabolic adaptation. This study aimed to determine the temporal profile of metabolic responses of the liver to cold exposure and changes in the hepatic NAD⁺ /SIRT system. Eight-week-old male C57BL/6 mice were individually housed in conventional cages under cold exposure (4 °C) for up to 5 days. Cold exposure decreased the hepatic triglyceride level and cholesterol level in mice by 1.7- and 1.6-fold, respectively. Lipogenic gene expression was persistently reduced, while gluconeogenic gene expression was transiently increased. Hepatic NAD⁺ /SIRT metabolism was induced during the 'cold remodeling' phase (days 1-3) and correlated with decreasing lipogenic and increasing gluconeogenic gene expression, contributing to the maintenance of whole-body lipid and glucose homeostasis.