A dietary supplementation with leucine and antioxidants is capable to accelerate muscle mass recovery after immobilization in adult rats

Prolonged inactivity induces muscle loss due to an activation of proteolysis and decreased protein synthesis; the latter is also involved in the recovery of muscle mass. The aim of the present work was to explore the evolution of muscle mass and protein metabolism during immobilization and recovery and assess the effect of a nutritional strategy for counteracting muscle loss and facilitating recovery. Adult rats (6-8 months) were subjected to unilateral hindlimb casting for 8 days (10-18) and then permitted to recover for 10 to 40 days (R10-R40). They were fed a Control or Experimental diet supplemented with antioxidants/polyphenols (AOX) (10 to 18), AOX and leucine (AOX + LEU) (18 to R15) and LEU alone (R15 to R40). Muscle mass, absolute protein synthesis rate and proteasome activities were measured in gastrocnemius muscle in casted and non-casted legs in post prandial (PP) and post absorptive (PA) states at each time point. Immobilized gastrocnemius protein content was similarly reduced (-37%) in both diets compared to the non-casted leg. Muscle mass recovery was accelerated by the AOX and LEU supplementation (+6% AOX+LEU vs. Control, P<0.05 at R40) due to a higher protein synthesis both in PA and PP states (+23% and 31% respectively, Experimental vs. Control diets, P<0.05, R40) without difference in trypsin-and chymotrypsin-like activities between diets. Thus, this nutritional supplementation accelerated the recovery of muscle mass via a stimulation of protein synthesis throughout the entire day (in the PP and PA states) and could be a promising strategy to be tested during recovery from bed rest in humans

Liver glycogen stores via 13C magnetic resonance spectroscopy in healthy children: randomized, controlled study

BackgroundOwing to its role in glucose homeostasis, liver glycogen concentration ([LGly]) can be a marker of altered metabolism seen in disorders which impact health of children. However, there is a paucity of normative data for this measure in children to allow comparison with patients, and time-course assessment of [LGly] in response to feeding has not been reported. 13C-magnetic resonance spectroscopy (13C-MRS) is used extensively in research to non-invasively assess liver metabolites in adult health and disease, but similar measurements in children are lacking.ObjectiveThe main objectives were to quantify the depletion of [LGly] after overnight fasting, and the subsequent response to feeding.DesignIn a randomized, open-label, incomplete block design study, healthy, normal-weight children (8-12y) attended 2 evening visits, each separated by ≥5 days and directly followed by a morning visit. An individually tailored, standardized meal was consumed 3-hours prior to evening assessments. Participants then remained fasted until the morning visit. [LGly] was assessed once in the fed (20:00hrs) and fasted state (08:00hrs) using 13C-MRS. After the 8:00hrs assessment, 200ml of a mixed-macronutrient drink containing 15.5g (402kJ) or 31g carbohydrate (804kJ), or water only, was consumed, with 13C-MRS measurements then performed hourly for 4h. Each child was randomized to 2 of 3 drink options across the 2 mornings. Data are expressed as mean (SD).ResultsTwenty-four children (13F:11M) completed the study (9.9(1.1)y, BMI percentile 45.7(25.9)). [LGly] decreased from 377.9(141.3) to 277.3(107.4) mmol·l-1 overnight; depletion rate 0.14(0.15) mmol·l-1·min-1. Incremental responses of [LGly] to test drinks differed (P<0.001), with incremental net AUC of [LGly] over 4h (i.netAUC240min) being higher for 15.5g (-67.1(205.8) mmol·l-1·240min; P<0.01) and 31g carbohydrate (101.6(180.9) mmol·l-1·240min; P<0.005) compared to water (-253.1(231.2) mmol·l-1·240min).ConclusionAfter overnight fasting, [LGly] decreased by 22.9(25.1)%, and [LGly] i.netAUC240min was higher after subsequent consumption of 15.5g and 31g carbohydrate, compared to water.Clinical Trial Registry number: NCT04278209 (www.clinicaltrials.gov

Contribution des tissus du système immunitaire au métabolisme protéique dans les situations d'agression aiguës et chroniques

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Beneficial effect of amino acid supplementation, especially cysteine, on body nitrogen economy in septic rats

Article originalInternational audienceBACKGROUND AND AIMS: Muscle wasting and increased synthesis of proteins and compounds involved in host defense characterize severe injury. The aims of the studies reported were to determine which amino acids exhibited an increased tissue content linked to anabolic processes in infected rats by comparison with healthy pair-fed controls, and to explore whether diets supplemented with these amino acids attenuate the catabolic response to infection. METHODS: Total amino acid content of the liver and the rest of the body were measured in control well-fed rats, in infected rats and their pair-fed controls 2 days after infection. In the nutritional protocols, infected rats were fed with a diet supplemented with alanine (basal diet), or threonine, serine, aspartate, asparagine and arginine (AA) or AA+cysteine (complete diet). RESULTS: Infection significantly increased liver total amino acid content by 38% for most amino acids. In contrast, the percentage increase was cysteine 79.3, threonine 45.3, aspartate-asparagine 46.3 and serine 46.5. Whole body without liver content of most amino acids decreased after infection due to the catabolic response, while the content of cysteine increased by 6% (P<0.05) and those of threonine and arginine did not decrease. After infection, animals fed the complete diet lost less weight than animals fed the basal diet (P<0.05). Furthermore, AA plus cysteine supplementation reduced significantly urinary nitrogen excretion and muscle wasting. CONCLUSIONS: The results provide evidence that diet supplementation with cysteine, threonine, serine, aspartate-asparagine and arginine supports the synthesis of vital proteins to spare body protein catabolism during infection

Long-term cysteine fortification impacts cysteine/glutathione homeostasis and food intake in ageing rats

International audienceHealthy ageing is associated with higher levels of glutathione. The study aimed to determine whether long-term dietary fortification with cysteine increases cysteine and glutathione pools, thus alleviating age-associated low-grade inflammation and resulting in global physiological benefits. The effect of a 14-week dietary fortification with cysteine was studied in non-inflamed (NI, healthy at baseline) and in spontaneously age-related low-grade inflamed (LGI, prefrail at baseline) 21-month-old rats. Fifty-seven NI rats and 14 LGI rats received cysteine-supplemented diet (4.0 g/kg of free cysteine added to the standard diet containing 2.8 g/kg cysteine). Fifty-six NI rats and 16 LGI rats received a control alanine-supplemented diet. Cysteine fortification in NI rats increased free cysteine (P < 0.0001) and glutathione (P < 0.03) in the liver and the small intestine. In LGI rats, cysteine fortification increased total non-protein cysteine (P < 0.0007) and free cysteine (P < 0.03) in plasma, and free cysteine (P < 0.02) and glutathione (P < 0.01) in liver. Food intake decreased over time in alanine-fed rats (r (2) = 0.73, P = 0.0002), whereas it was constant in cysteine-fed rats (r (2) = 0.02, P = 0.68). Cysteine fortification did not affect inflammatory markers, mortality, body weight loss, or tissue masses. Doubling the dietary intake of cysteine in old rats increased cysteine and glutathione pools in selected tissues. Additionally, it alleviated the age-related decline in food intake. Further validation of these effects in the elderly population suffering from age-related anorexia would suggest a useful therapeutic approach to the problem

The inflammatory response to vaccination is altered in the elderly

International audienceTo further explore whether immune function and acute phase response are altered during ageing, the response to a mild inflammatory stress (DT-Polio-Typhim vaccination) was studied in elderly and young subjects. Cytokine production (IFN-gamma, TNF-alpha, IL-6, IL-10) by whole blood cultures, circulating cytokines and acute phase proteins were analysed before and 2 days after vaccination. Prior to vaccination, only IFN-gamma production was lower in the elderly than in the young subjects due to a lower mononuclear cell number. In the same time, although in the normal range, several acute phase proteins were greater in elderly than in young subjects, suggesting a low-grade inflammatory state in the elderly. After vaccination, IFN-gamma production remained lower in the elderly than in the young, supporting an altered cell-mediated immunity with advancing age. TNF-alpha production was unaffected by either ageing or vaccination. IL-6 production was stimulated by vaccination in young subjects but not significantly in the elderly. IL-10 production was inhibited by vaccination in the elderly but not in the young. Acute phase proteins were less increased in elderly than in young subjects. Taken together, these results support a general lack of inflammatory response in the elderly exposed to an immune challenge and suggest that immune deficiency may concern both Th1 and Th2 responses. However, the interpretation must respect the limitation of small subjects number

Methionine transsulfuration is increased during sepsis in rats

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Nutritional method

International Application No: PCT/EP2006/063229 Publication Date: 21.12.2006 International Filing Date: 14.06.2006A method of improving nutrition and/or treating low grade inflammation in an elderly human subject comprises administering to said subject a cysteine source so as to provide metabolically available cysteine in the diet of said subject in a proportion relative to all available amino acids which is greater that the proportion of cysteine relative to all amino acids which corresponds to the requirements of a healthy young human subject

Modulation of skeletal muscle lactate metabolism following bacteremia by insulin or insulin-like growth factor-i

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