C. Dietary protein regulates hepatic constitutive protein anabolism in rats in a dose-dependent manner and independently of energy nutrient composition. We had previously observed that drastic increases in protein consumption greatly modified hepatic protein anabolism in rats, but the confounding effects of other macronutrient changes or a moderate protein increase to generate the same modifications have not yet been established. This study examined the metabolic and hormonal responses of rats

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... ubjected to 14-day isoenergetic diets containing normal, intermediate, or high-protein levels (NP: 14% of energy, IP: 33%, HP: 50%) and different carbohydrate (CHO) to fat ratios within each protein level. Fasted or fed rats (n ϭ 104) were killed after the injection of a flooding dose of 13 C-valine. The hepatic protein content increased in line with the dietary protein level (P Ͻ 0.05). The hepatic fractional synthesis rates (FSR) of protein were significantly influenced by both the protein level and the nutritional state (fasted vs. fed) (P Ͻ 0.0001) but not by the CHO level, reaching on average 110%/day, 92%/day, and 83%/day in rats fed the NP, IP, and HP diets, respectively. The FSR of plasma albumin and muscle did not differ between diets, while feeding tended to increase muscle FSR. Proteolysis, especially the proteasome-dependent system, was down-regulated in the fed state in the liver when protein content increased. Insulin decreased with the CHO level in the diet. Our results reveal that excess dietary protein lowers hepatic constitutive, but not exported, protein synthesis rates, independently of the other macronutrients, and related changes in insulin levels. This response was observed at the moderate levels of protein intake (33%) that are plausible in a context of human consumption. high-protein diet; liver; energy nutrients