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 subjected 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 = 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 < 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 < 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 diets differentially modulate protein content and protein synthesis in visceral and peripheral tissues in rats.

OBJECTIVE: High-protein diets give rise to increased amplitude in the diurnal cycling of protein gains and losses at the whole-body level, but the tissue localization and mechanisms underlying these metabolic adaptations remain unclear. We investigated tissue-specific responses to increasing protein intakes in rats. METHODS: Protein synthesis rates (flooding dose with (13)C-valine) and accretion were assessed in individual tissues of fasted or fed rats (n = 32) after a 2-wk adaptation to a normal- or high-protein (HP) diet. RESULTS: In livers of HP rats, a strong inhibition of protein synthesis rates (-34%) occurred in the fasted and fed states, whereas a higher protein content (+10%) was observed. In the kidneys, a slight inhibition of synthesis rates after the HP diet was also observed but remained without effect on kidney protein pool size. Stomach and skin protein synthesis rates were significantly increased under HP conditions, whereas protein anabolism in skeletal muscle remained insensitive to the dietary protein level. This was also true for specific muscle protein fractions: myosin, mitochondrial, or sarcoplasmic protein synthesis rates were influenced by neither the dietary protein level nor the nutritional status. CONCLUSION: Modulation of protein kinetics and accretion by the HP diet is tissue-specific and the liver plays a critical role in such adaptations in a unique situation associating an inhibition of protein synthesis and protein pool expansion. The mechanisms underlying these changes and their physiologic incidence remain to be elucidated.