Protein depletion and replenishment in mice: different roles of muscle and liver

Abstract

Fully grown male CD-1 mice, fed a protein-free diet for 3 days, received 1 g of starch with or without 300 mg casein by intragastric intubation. We surveyed the acute effects of these nutrients on protein synthesis in all tissues (by extrapolating to infinity the incorporation of radioactive leucine after its injection in massive doses) and protein degradation in skeletal muscle and liver (by the accumulation of bestatin-induced peptide intermediates). Muscle proteolysis was the major source of N during depletion. Compared with postabsorptive animals, starch suppressed muscle protein loss (synthesis +21%, degradation −24%, P < 0.01) and stimulated hepatic proteolysis (degradation +28%, P < 0.01). Addition of casein to the starch was anabolic in liver (synthesis +41%, degradation −33%, P < 0.01), gastrointestinal tract, pancreas, and skin (synthesis +38, +69 and +38%, respectively, P < 0.01) but had no effect on muscle. Protein turnover proved uniquely sensitive to the dietary supply of carbohydrates in muscle and to the endogenous or exogenous supply of amino acids in liver.

Absorption kinetics are a key factor regulating postprandial protein metabolism in response to qualitative and quantitative variations in protein intake

“…The model also predicted that meal ingestion gave rise to a strong splanchnic anabolic response, since ϳ70% of the total 8-h postprandial accretion of Nm concerned splanchnic proteins, which is consistent with our current knowledge of the system (1,17,71) and previous findings of compartmental modeling of Nm postprandial interorgan metabolism (32,33,36). This result is in agreement with the idea that the acute anabolic effect of a mixed meal occurs primarily in the splanchnic area (24,60,72,77), while muscle protein synthesis only makes a minor contribution to the wholebody postprandial anabolic response, despite the large mass of muscle (57,68,80). In addition, the model predicted a recycling efficiency of dietary urea N ranging from 5% to 25% at the end of the postprandial period, in line with previous findings in the literature (6,30,50,56).…”

Contribution of plasma proteins to splanchnic and total anabolic utilization of dietary nitrogen in humans

“…For instance, the synthesis of albumin (the most abundant plasma protein), which takes place exclusively in the liver, has been reported to be regulated by insulin and enteral AA delivery, levels of which rise dramatically after the ingestion of a mixed meal (16,17,30,52,54). The acute anabolic effect of a mixed meal thus occurs primarily in the splanchnic area (16,17,25,38,44,49,52,54), whereas muscle protein synthesis makes only a minor contribution to the whole body anabolic response despite the large mass of muscle (37,56). It is believed that the splanchnic anabolic processes allow for the sparing of dietary N from deamination through the temporary "storage" of ingested AA in the labile splanchnic protein pool (17,45,48,50,57) while simultaneously buffering the peripheral tissues from excessive changes in free AA concentrations (1,45,47).…”

Energy nutrients modulate the splanchnic sequestration of dietary nitrogen in humans: a compartmental analysis

“…protein metabolism; postprandial period; insulin; mathematical model; parameter estimation CONSIDERABLE ATTENTION has been paid to interactions between energy nutrients and nitrogen (N) metabolism, leading to the conclusion that carbohydrate (CHO) is more likely than fat to exert a sparing effect on body protein (25,30,33,42). Certain studies have addressed the effects of dietary CHO (33,48) or insulin availability (32) on splanchnic N anabolism in the fed state, whereas others have aimed at studying the effects of amino acids (AA), CHO, and/or insulin on the stimulation of muscle protein synthesis (5,11,41,44). However, little is still known, particularly in humans, about the dietary N partitioning between splanchnic and peripheral tissues and its immediate orientation in the anabolic and catabolic pathways of different organs after protein ingestion.…”

“…The balance between dietary AA anabolic and catabolic pathways depends on the tissue under consideration and varies as a function of dietary factors, especially protein or energy intake (2,49). Liver and muscle, the most important tissues involved in postprandial protein turnover, do not participate in these metabolic processes in the same way because of their different specificity (high rate of protein turnover in the liver vs. large mass of the muscle protein pool) (33).…”