High-protein diets differentially modulate protein content and protein synthesis in visceral and peripheral tissues in rats

Abstract 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 with13 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.