Background: Muscle mass maintenance is largely regulated by basal muscle protein synthesis and the capacity to stimulate muscle protein synthesis aft

Background: Anemia is a major complication of end stage renal disease. The anemia is mainly the result of impaired formation of erythrocytes due to lack of erythropoietin and iron deficiency. Compelling evidence, however, points to the contribution of accelerated erythrocyte death, which decreases the life span of circulating erythrocytes. Erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by cell membrane scrambling with phosphatidylserine-exposure at the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i). Erythrocytes could be sensitized to cytosolic Ca²⁺ by ceramide. In end stage renal disease, eryptosis may possibly be stimulated by uremic toxins. The present study explored, whether the uremic toxin acrolein could trigger eryptosis. Methods: Cell volume was estimated from forward scatter, phosphatidylserine-exposure from annexin-V-binding, hemolysis from hemoglobin release, [Ca²⁺]_i from Fluo3-fluorescence, and ceramide from fluorescent antibodies. Results: A 48 h exposure to acrolein (30 － 50 µM) did not significantly modify [Ca²⁺]_i but significantly decreased forward scatter and increased annexin-V-binding. Acrolein further triggered slight, but significant hemolysis and increased ceramide formation in erythrocytes. Acrolein (50 µM) induced annexin-V-binding was significantly blunted in the nominal absence of extracellular Ca²⁺. Acrolein augmented the annexin-V-binding following treatment with Ca²⁺ ionophore ionomycin (1 µM). Conclusion: Acrolein stimulates suicidal erythrocyte death or eryptosis, an effect at least in part due to stimulation of ceramide formation with subsequent sensitisation of the erythrocytes to cytosolic Ca²⁺.

O assess whether resistance-type exercise performed in the evening increases the overnight muscle protein synthetic response to presleep protein ingestion. Methods Twenty-four healthy young men were randomly assigned to ingest 30 g intrinsically L-[1-13C]-phenylalanine and L-[1-13C]-leucine-labeled casein protein before going to sleep with (PRO + EX, n = 12) or without (PRO, n = 12) prior resistance-type exercise performed in the evening. Continuous intravenous L-[ring-2H5]-phenylalanine, L-[1-13C]-leucine, and L-[ring-2H2]-tyrosine infusions were applied. Blood and muscle tissue samples were collected to assess whole-body protein balance, myofibrillar protein synthesis rates, and overnight incorporation of dietary protein-derived amino acids into de novo myofibrillar protein. Results A total of 57% ± 1% of the ingested protein-derived phenylalanine appeared in the circulation during overnight sleep. Overnight myofibrillar protein synthesis rates were 37% (0.055%·h−1 ± 0.002%·h−1 vs. 0.040%·h−1 ± 0.003%·h−1, P < 0.001, based on L-[ring-2 H5]-phenylalanine) and 31% (0.073%·h−1 ± 0.004%·h−1 vs. 0.055%·h−1 ± 0.006%·h−1, P = 0.024, based on L-[1-13C]-leucine) higher in PRO + EX compared with PRO. Substantially more of the dietary protein-derived amino acids were incorporated into de novo myofibrillar protein during overnight sleep in PRO + EX compared with PRO (0.026 ± 0.003 vs. 0.015 ± 0.003 molar percent excess, P = 0.012). Conclusions Resistance-type exercise performed in the evening augments the overnight muscle protein synthetic response to presleep protein ingestion and allows more of the ingested protein-derived amino acids to be used for de novo myofibrillar protein synthesis during overnight sleep....

Muscle loss is a severe complication of many medical conditions such as cancer, cardiac failure, muscular dystrophies, and nerve damage. The contribution of myofibrillar protein synthesis (MPS) to the loss of muscle mass after nerve damage is not clear. Using deuterium oxide (D₂O) labeling, we demonstrate that MPS is significantly increased in rat m. tibialis anterior (TA) compared to control (3.23 ± 0.72 [damaged] to 2.09 ± 0.26%^∗day⁻¹ [control]) after 4 weeks of nerve constriction injury. This is the case despite substantial loss of mass of the TA (350 ± 96 mg [damaged] to 946 ± 361 mg [control]). We also show that expression of regulatory proteins involved with MPS (p70s6k1: 2.4 ± 0.3 AU [damaged] to 1.8 ± 0.2 AU [control]) and muscle protein breakdown (MPB) (MAFbx: 5.3 ± 1.2 AU [damaged] to 1.4 ± 0.4 AU [control]) are increased in nerve damaged muscle. Furthermore, the expression of p70s6k1 correlates with MPS rates (r² = 0.57). In conclusion, this study shows that severe muscle wasting following nerve damage is accompanied by increased as opposed to decreased MPS.

The large decrease in body weight with glucagon-like peptide-1 (GLP-1) medicines raises concern about a loss of lean body mass (LBM) and skeletal muscle. In this work, we present four pre-clinical studies and a proof-of-concept clinical trial that address this issue. We report that in obese mice, GLP-1 medicines predominantly reduce body fat alongside a small but significant decrease in LBM. Among lean tissues, loss of liver mass exceeds change in muscle mass. While absolute muscle mass and strength decrease, relative muscle mass and strength improve, resulting in better running performance. Interestingly, while atrophy is similar during immobilization, GLP-1 medicines have a distinct effect on the muscle proteome compared to calorie restriction. Patients with obesity on GLP-1 medicines improve their body composition without negatively affecting strength. Overall, in middle-aged mice and men, GLP-1 medicines slightly decrease absolute muscle values but positively impact body composition and mobility. The clinical trial is registered on clinicaltrials.gov (NCT05606471).