Excessive intake of fructose increases lipogenesis in the liver, leading to hepatic lipid accumulation and development of fatty liver disease. Metabolic alterations in the liver due to fructose intake have been reported in many studies, but the effect of fructose administration on hepatic gluconeogenesis is not fully understood. The aim of this study was to evaluate the acute effects of fructose administration on fasting-induced hepatic gluconeogenesis. C57BL/6J mice were administered fructose solution after 14 h of fasting and plasma insulin, glucose, free fatty acids, and ketone bodies were analysed. We also measured phosphorylated AKT and forkhead box O (FoxO) 1 protein levels and gene expression related to gluconeogenesis in the liver. Furthermore, we measured glucose production from pyruvate after fructose administration. Glucose-administered mice were used as controls. Fructose administration enhanced phosphorylation of AKT in the liver, without increase of blood insulin levels. Blood free fatty acids and ketone bodies concentrations were as high as those in the fasting group after fructose administration, suggesting that insulin-induced inhibition of lipolysis did not occur in mice administered with fructose. Fructose also enhanced phosphorylation of FoxO1 and suppressed gluconeogenic gene expression, glucose-6-phosphatase activity, and glucose production from pyruvate. The present study suggests that acute fructose administration suppresses fasting-induced hepatic gluconeogenesis in an insulin-independent manner.
We investigated whether the deletion of glycerol-3-phosphate dehydrogenase (GPD) 1 would affect carbohydrate oxidation, fat oxidation, and body weight by using the GPD1 null mice (BALB/cHeA (HeA)). We found that fat oxidation in HeA mice was significantly high during the early active phase than in BALB/cBy (By) mice used as a control under ad libitum conditions. Metabolic tracer experiment revealed that fatty acid oxidation in the skeletal muscle of HeA mice tended to be high. The energy expenditure and fat oxidation in HeA mice under fasting conditions were significantly higher than that in the By mice. Moreover, we monitored body weight gain in HeA mice under ad libitum feeding and found lower body weight gain. These data indicate that GPD1 deficiency induces enhancement of fat oxidation with suppression of weight gain. We propose that GPD1 deletion contributes to the reduction of body weight gain via enhancement of fat oxidation.
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