Endurance-Type Exercise Increases Bulk and Individual Mitochondrial Protein Synthesis Rates in Rats.

Physical activity increases muscle protein synthesis rates. However, the impact of exercise on the coordinated up- and/or downregulation of individual protein synthesis rates in skeletal muscle tissue remains unclear. The authors assessed the impact of exercise on mixed muscle, myofibrillar, and mitochondrial protein synthesis rates as well as individual protein synthesis rates in vivo in rats. Adult Lewis rats either remained sedentary (n = 3) or had access to a running wheel (n = 3) for the last 2 weeks of a 3-week experimental period. Deuterated water was injected and subsequently administered in drinking water over the experimental period. Blood and soleus muscle were collected and used to assess bulk mixed muscle, myofibrillar, and mitochondrial protein synthesis rates using gas chromatography-mass spectrometry and individual muscle protein synthesis rates using liquid chromatography-mass spectrometry (i.e., dynamic proteomic profiling). Wheel running resulted in greater myofibrillar (3.94 ± 0.26 vs. 3.03 ± 0.15%/day; p < .01) and mitochondrial (4.64 ± 0.24 vs. 3.97 ± 0.26%/day; p < .05), but not mixed muscle (2.64 ± 0.96 vs. 2.38 ± 0.62%/day; p = .71) protein synthesis rates, when compared with the sedentary condition. Exercise impacted the synthesis rates of 80 proteins, with the difference from the sedentary condition ranging between -64% and +420%. Significantly greater synthesis rates were detected for F1-ATP synthase, ATP synthase subunit alpha, hemoglobin, myosin light chain-6, and synaptopodin-2 (p < .05). The skeletal muscle protein adaptive response to endurance-type exercise involves upregulation of mitochondrial protein synthesis rates, but it is highly coordinated as reflected by the up- and downregulation of various individual proteins across different bulk subcellular protein fractions

Dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during short-term bed rest

This is the author accepted manuscript. The final version is available from the American Physiological Society via the DOI in this record.Short periods of bed rest lead to the loss of muscle mass and quality. It has been speculated that dietary feeding pattern may impact upon muscle protein synthesis rates and, therefore, modulate the loss of muscle mass and quality. We subjected 20 healthy men (age: 25±1 y, BMI: 23.8±0.8 kg·m-2) to one week of strict bed rest with intermittent (4 meals/day) or continuous (24 h/day) enteral tube feeding. Participants consumed deuterium oxide for 7 days prior to bed rest and throughout the 7-day bed rest period. Prior to and immediately after bed rest, lean body mass (DXA), quadriceps cross-sectional area (CSA; CT), maximal oxygen uptake capacity (VO2peak), and whole-body insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) were assessed. Muscle biopsies were collected 7 days prior to, 1 day prior to, and immediately after bed rest to assess muscle tracer incorporation. Bed rest resulted in 0.3±0.3 vs 0.7±0.4 kg lean tissue loss and a 1.1±0.6 vs 0.8±0.5% decline in quadriceps CSA in the intermittent vs continuous feeding group, respectively (both P0.05). Moreover, feeding pattern did not modulate the bed rest-induced decline in insulin sensitivity (-46±3% vs 39±3%; P0.05). Myofibrillar protein synthesis rates during bed rest did not differ between the intermittent and continuous feeding group (1.33±0.07 vs 1.50±0.13%·d−1, respectively; P>0.05). In conclusion, dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during one week of bed rest in healthy men

Short-term muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates

This is the author accepted manuscript. The final version is available from the American Physiological Society via the DOI in this recordIntroduction: Short-term muscle disuse has been reported to lower both post-absorptive and post-prandial myofibrillar protein synthesis rates. This study assessed the impact of disuse on daily myofibrillar protein synthesis rates following acute (2 days) and more prolonged (7 days) muscle disuse under free living conditions. Methods: Thirteen healthy young men (age, 20±1 y; BMI, 23±1 kg·m-2) underwent 7 days of unilateral leg immobilization via a knee brace with the non-immobilized leg acting as a control. Four days prior to immobilization participants ingested 400 mL 70% deuterated water, with 50 mL doses consumed daily thereafter. Upper leg bilateral MRI scans and muscle biopsies were collected before, and after 2 and 7 days of immobilization to determine quadriceps volume and daily myofibrillar protein synthesis rates. Results: Immobilization reduced quadriceps volume in the immobilized leg by 1.7±0.3 and 6.7±0.6 % after 2 and 7 days, respectively, with no changes in the control leg. Over the one week immobilization period myofibrillar protein synthesis rates were 36±4% lower in the immobilized (0.81±0.04%·d-1) compared with the control (1.26±0.04%·d-1) leg (P<0.001). Myofibrillar protein synthesis rates in the control leg did not change over time (P=0.775), but in the immobilized leg were numerically lower during the 0-2 day period (16±6%, 1.11±0.09%·d-1, P=0.153) and were significantly lower during the 2-7 day period (44±5%, 0.70±0.06%·d-1, P<0.001) when compared with the control leg. Conclusion: One week of muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates in healthy young men.University of MaastrichtRoyal SocietyUniversity of ExeterNational Institute for Health Research (NIHR

The influence of population characteristics on variation in general practice based morbidity estimations

Contains fulltext : 96442.pdf (publisher's version ) (Open Access

Estimating loss of Brucella abortus antibodies from age-specific serological data in elk

Serological data are one of the primary sources of information for disease monitoring in wildlife. However, the duration of the seropositive status of exposed individuals is almost always unknown for many free-ranging host species. Directly estimating rates of antibody loss typically requires difficult longitudinal sampling of individuals following seroconversion. Instead, we propose a Bayesian statistical approach linking age and serological data to a mechanistic epidemiological model to infer brucellosis infection, the probability of antibody loss, and recovery rates of elk (Cervus canadensis) in the Greater Yellowstone Ecosystem. We found that seroprevalence declined above the age of ten, with no evidence of disease-induced mortality. The probability of antibody loss was estimated to be 0.70 per year after a five-year period of seropositivity and the basic reproduction number for brucellosis to 2.13. Our results suggest that individuals are unlikely to become re-infected because models with this mechanism were unable to reproduce a significant decline in seroprevalence in older individuals. This study highlights the possible implications of antibody loss, which could bias our estimation of critical epidemiological parameters for wildlife disease management based on serological data

The muscle protein synthetic response to carbohydrate and protein ingestion is not impaired in men with longstanding type 2 diabetes.

Protein ingestion stimulates muscle protein synthesis and improves net muscle protein balance. Insulin resistance has been suggested to result in a reduced muscle protein synthetic response to food intake. As such, we hypothesized that type 2 diabetes patients have a impaired muscle protein synthetic response to food ingestion. To test this hypothesis, 10 male type 2 diabetes patients using their normal oral glucose-lowering medication (68 +/- 2 y) and 10 matched, normoglycemic men (65 +/- 2 y) were randomly assigned to 2 crossover treatments in which whole body and muscle protein synthesis were measured following the consumption of either carbohydrate (CHO) or carbohydrate with a protein hydrolysate (CHO+PRO). Primed, continuous infusions with L-[ring-13C6]phenylalanine and L-[ring-2H2]tyrosine were applied and blood and muscle samples were collected to assess whole-body protein balance and mixed muscle protein fractional synthetic rate over a 6-h period. Whole-body phenylalanine and tyrosine flux were higher after the CHO+PRO treatment compared with the CHO treatment in the diabetes and control group (P < 0.01). Protein balance was negative following CHO but positive following CHO+PRO treatment in both groups. Muscle protein synthesis rates were higher in both groups following the CHO+PRO (0.086 +/- 0.014%/h) treatment than in the CHO treatment (0.040 +/- 0.003%/h; P < 0.01) with no difference between the diabetes patients and normoglycemic controls. We conclude that the muscle protein synthetic response to CHO or CHO+PRO ingestion is not substantially impaired in longstanding, type 2 diabetes patients treated with oral blood glucose-lowering medication

A single session of neuromuscular electrical stimulation does not augment postprandial muscle protein accretion

The loss of muscle mass and strength that occurs with aging, termed sarcopenia, has been (at least partly) attributed to an impaired muscle protein synthetic response to food intake. Previously, we showed that neuromuscular electrical stimulation (NMES) can stimulate fasting muscle protein synthesis rates and prevent muscle atrophy during disuse. We hypothesized that NMES prior to protein ingestion would increase postprandial muscle protein accretion. Eighteen healthy elderly (69 ± 1 yr) males participated in this study. After a 70-min unilateral NMES protocol was performed, subjects ingested 20 g of intrinsically l-[1-(13)C]phenylalanine-labeled casein. Plasma samples and muscle biopsies were collected to assess postprandial mixed muscle and myofibrillar protein accretion as well as associated myocellular signaling during a 4-h postprandial period in both the control (CON) and stimulated (NMES) leg. Protein ingestion resulted in rapid increases in both plasma phenylalanine concentrations and l-[1-(13)C]phenylalanine enrichments, which remained elevated during the entire 4-h postprandial period (P 0.05). In agreement, no differences were observed in the postprandial rise in myofibrillar protein bound l-[1-(13)C]phenylalanine enrichments between the CON and NMES legs (0.0115 ± 0.0014 vs. 0.0133 ± 0.0013 MPE, respectively, P > 0.05). Significant increases in mTOR and P70S6K phosphorylation status were observed in the NMES-stimulated leg only (P < 0.05). We conclude that a single session of NMES prior to food intake does not augment postprandial muscle protein accretion in healthy older men.We gratefully acknowledge the enthusiastic support of Rinske Franssen (NUTRIM School of Nutrition and Translational Research in Metabolism) in this study

Co-ingestion of protein and leucine stimulates muscle protein synthesis rates to the same extent in young and elderly lean men.

BACKGROUND: The progressive loss of skeletal muscle mass with aging is attributed to a disruption in the regulation of skeletal muscle protein turnover. OBJECTIVE: We investigated the effects on whole-body protein balance and mixed-muscle protein synthesis rates of the ingestion of carbohydrate with or without protein and free leucine after simulated activities of daily living. DESIGN: Eight elderly (75 +/- 1 y) and 8 young (20 +/- 1 y) lean men were randomly assigned to 2 crossover experiments in which they consumed either carbohydrate (CHO) or carbohydrate plus protein and free leucine (CHO+Pro+Leu) after performing 30 min of standardized activities of daily living. Primed, continuous infusions with L-[ring-13C6]phenylalanine and L-[ring-2H2]tyrosine were applied, and blood and muscle samples were collected to assess whole-body protein turnover and the protein fractional synthetic rate in the vastus lateralis muscle over a 6-h period. RESULTS: Whole-body phenylalanine and tyrosine flux were significantly higher in the young than in the elderly men (P < 0.01). Protein balance was negative in the CHO experiment but positive in the CHO+Pro+Leu experiment in both groups. Mixed-muscle protein synthesis rates were significantly greater in the CHO+Pro+Leu than in the CHO experiment in both the young (0.082 +/- 0.005%/h and 0.060 +/- 0.005%/h, respectively; P < 0.01) and the elderly (0.072 +/- 0.006%/h and 0.043 +/- 0.003%/h, respectively; P < 0.01) subjects, with no significant differences between groups. CONCLUSIONS: Co-ingestion of protein and leucine with carbohydrate after activities of daily living improves whole-body protein balance, and the increase in muscle protein synthesis rates is not significantly different between lean young and elderly men