Combined effect of citrulline and lactoserum on amino acid availability in aged rats.

OBJECTIVE: Age-associated sarcopenia is due to anabolic resistance to feeding. Muscle protein synthesis is improved by fast proteins (e.g., lactoserum), which increase peripheral amino acid (AA) bioavailability more rapidly than slow proteins (e.g., casein), and by citrulline. Citrulline, which limits splanchnic sequestration of AA, may more effectively increase peripheral AA bioavailability when combined with lactoserum than with casein when administered as an oral nutritional protein supplement. METHODS: In this study, 25 fasted aged rats received a single gavage administration of lactoserum or casein 0.4 g/kg, alone or with citrulline 0.4 g/kg, and AA pharmacokinetics, glucose, insulin, triglycerides, and insulin-like growth factor 1 (IGF1) were monitored for 4 h. At 4 h, muscle protein and AA contents and protein synthesis activation were measured. RESULTS: While lactoserum was associated with higher AA availability, citrulline exerts only limited effects on the plasma profile of AAs from the two proteins. Maximum plasma citrulline was reached earlier with casein (T90 min) than with lactoserum (T120 min). A protein x citrulline interaction was observed for some plasma and muscle AA levels with a significant activation of mechanistic target of rapamycin complex 1 (mTORC1) signaling suggesting higher anabolism with the combination of citrulline and lactoserum. Lower plasma and muscle AA levels with citrulline and lactoserum compared to lactoserum alone suggest a greater AA utilization in a context of muscle anabolic signaling activation. CONCLUSION: Provision of a citrulline-lactoserum combination as a nutritional supplement could therefore be beneficial in terms of muscle protein balance and prevention of sarcopenia. Further studies are warranted to evaluate the efficacy of this combination.

Lkb1 suppresses amino acid-driven gluconeogenesis in the liver.

Excessive glucose production by the liver is a key factor in the hyperglycemia observed in type 2 diabetes mellitus (T2DM). Here, we highlight a novel role of liver kinase B1 (Lkb1) in this regulation. We show that mice with a hepatocyte-specific deletion of Lkb1 have higher levels of hepatic amino acid catabolism, driving gluconeogenesis. This effect is observed during both fasting and the postprandial period, identifying Lkb1 as a critical suppressor of postprandial hepatic gluconeogenesis. Hepatic Lkb1 deletion is associated with major changes in whole-body metabolism, leading to a lower lean body mass and, in the longer term, sarcopenia and cachexia, as a consequence of the diversion of amino acids to liver metabolism at the expense of muscle. Using genetic, proteomic and pharmacological approaches, we identify the aminotransferases and specifically Agxt as effectors of the suppressor function of Lkb1 in amino acid-driven gluconeogenesis.