Plant protein, fibre and physical activity solutions to address poor appetite and prevent undernutrition in older adults: study protocol for the APPETITE randomised controlled trial.

Reduced appetite with ageing is a key factor that may increase risk of undernutrition. The objective of this study is to determine the impact of innovative plant protein fibre (PPF) products within a personalised optimised diet (PD), a physical activity (PA) programme, and their combination on appetite, and other nutritional, functional and clinical outcomes in community-dwelling older adults in a multi-country randomised controlled intervention trial. One hundred and eighty community-dwelling adults (approximately sixty per trial centre in Germany, Ireland and Italy) aged 65 years and over will be recruited to participate in a 12-week, parallel-group, controlled trial. Participants will be randomised into one of four groups: 1, PD (incorporating two PPF products): 2, PA; 3, PD + PA; and 4, no intervention (control). The primary outcome is appetite measured by visual analogue scales and energy intake from an ad libitum test meal. Secondary outcomes include fasting and postprandial appetite-related gut hormones, Simplified Nutritional Appetite Questionnaire score, body composition, cardiorespiratory fitness, muscle strength, physical function and PA. In addition, self-efficacy, cognitive status, dietary restraint, depressive symptoms and compliance and acceptability of the intervention will be assessed. Metabolomic profiles, RMR, muscle motor unit properties and gut microbiome will also be assessed to explore potential underlying mechanisms. This multi-centre randomised controlled trial will advance knowledge on how PD (incorporating PPF products), PA and their combination influence appetite, nutritional status and related health outcomes in community-dwelling older adults and contribute to the prevention of undernutrition. Trial registration: Clinical Trials.gov Registry NCT05608707 (registered on 2 November 2022). Protocol Version: NCT05608707 Version 4 (registered on 29 September 2023).

Age-Dependent Serum Volatilomics of Milk and Yogurt Intake: A Randomized Crossover Study in Healthy Young and Older Men.

Nutritional biomarkers of dairy intake can be affected by both food transformation and the metabolic status of the consumer. To assess these effects, this study investigated the serum volatilome of 14 young (YA) and 14 older (OA) adult men undergoing a 3 week restriction of dairy and fermented foods followed by a randomized crossover acute intake of milk and yogurt. 3,5-Dimethyl-octan-2-one was identified as a potential marker of dairy product intake as its response after both milk and yogurt intake was significantly increased during the postprandial phase but significantly decreased in fasting serum samples of the OA group after the restriction phase. The postprandial response of two metabolites was significantly different for the two dairy products while 19 metabolites were modulated by age. Remarkably, the response of all age-dependent metabolites was higher in the OA than in the YA group after milk or yogurt intake, whereas at the end of the restriction phase, their fasting concentrations were lower in the OA than in the YA group. Among these, p-cresol, a specific marker of colonic protein fermentation, had a significant response in the OA but not the YA group, which may suggest impaired intestinal processing of dietary proteins in the OA group.

Targeting the gut to prevent and counteract metabolic disorders and pathologies during aging.

Impairment of gut function is one of the explanatory mechanisms of health status decline in elderly population. These impairments involve a decline in gut digestive physiology, metabolism and immune status, and associated to that, changes in composition and function of the microbiota it harbors. Continuous deteriorations are generally associated with the development of systemic dysregulations and ultimately pathologies that can worsen the initial health status of individuals. All these alterations observed at the gut level can then constitute a wide range of potential targets for development of nutritional strategies that can impact gut tissue or associated microbiota pattern. This can be key, in a preventive manner, to limit gut functionality decline, or in a curative way to help maintaining optimum nutrients bioavailability in a context on increased requirements, as frequently observed in pathological situations. The aim of this review is to give an overview on the alterations that can occur in the gut during aging and lead to the development of altered function in other tissues and organs, ultimately leading to the development of pathologies. Subsequently is discussed how nutritional strategies that target gut tissue and gut microbiota can help to avoid or delay the occurrence of aging-related pathologies.

Fructose Feeding during the Postabsorptive State Alters Body Composition and Spares Nitrogen in Protein-Energy-Restricted Old Rats.

Background: Fructose feeding in the context of high energy intake is recognized as being responsible for metabolic dysregulation. However, its consumption in the postabsorptive state might contribute to reducing the use of amino acids (AAs) as energy substrates and thus spare nitrogen resources, which could be beneficial during catabolic states. Objective: We hypothesized that fructose feeding during a catabolic situation corresponding to protein-energy restriction (PER) in older rats would reduce AA utilization for energy purposes, thus slowing down the loss of body weight (BW) and improving body composition. Methods: For 45 d, 22-mo-old male Wistar rats (average weight: 716 g) were fed a control ration (13% protein) either at normal (20 g/d), restricted (PER: 10 g/d), or at PER levels supplemented with glucose (3 g/d) or fructose (3 g/d) and then studied in the postabsorptive state. We measured BW, body composition, and enzyme activities and metabolite concentrations related to glucose, fructose, and AA metabolism. Results: Both glucose and fructose feeding reduced PER-induced loss of BW and lean mass (-27% compared with PER), but only fructose reduced the loss of fat mass (-28% compared with PER). Fructose feeding prevented the PER-induced loss of muscle and intestinal mass. Fructose feeding also reduced circulating branched-chain AA concentrations by 50% (compared with PER) and increased those of alanine (+65% compared with PER). A reduction in hepatic enzymes related to AA catabolism was also observed during fructose feeding (compared with PER), whereas glycogen concentrations were enhanced in both intestine (+300%) and muscle (+21%). Conclusions: We showed that in PER older rats, fructose feeding improved body composition and the weight of several organs by reducing AA catabolism and utilization for energy production and liver autophagy potential. This could be advantageous in sparing body proteins, particularly during catabolic states, such as those related to malnutrition during aging.

Metabolomics Reveals that the Type of Protein in a High-Fat Meal Modulates Postprandial Mitochondrial Overload and Incomplete Substrate Oxidation in Healthy Overweight Men.

Background: A meal rich in saturated fatty acids induces a postprandial metabolic challenge. The type of dietary protein may modulate postprandial metabolism. Objective: We studied the effect of dietary protein type on postprandial changes in the metabolome after a high-fat meal. Methods: In a 3-period, crossover, postprandial study, 10 healthy overweight men with an elevated waist circumference (>94 cm) ingested high-fat meals made up of cream fat (70% of energy), sucrose (15% energy), and protein (15% energy) from either casein (CAS), whey protein (WHE), or α-lactalbumin-enriched whey protein (LAC). Urine collected immediately before and 2, 4, and 6 h after the meal was analyzed for metabolomics, a secondary outcome of the clinical study. We used mixed-effect models, partial least-square regression, and pathway enrichment analysis. Results: At 4 and 6 h after the meal, the postprandial metabolome was found to be fully discriminated according to protein type. We identified 17 metabolites that significantly explained the effect of protein type on postprandial metabolomic changes (protein-time interaction). Among this signature, acylcarnitines and other acylated metabolites related to fatty acid or amino acid oxidation were the main discriminant features. The difference in metabolic profiles was mainly explained by urinary acylcarnitines and some other acylated products (protein type, Ps < 0.0001), with a dramatically greater increase (100- to 1000-fold) after WHE, and to a lesser extent after LAC, as compared with CAS. Pathway enrichment analysis confirmed that the type of protein had modified fatty acid oxidation (P < 0.05). Conclusion: Taken together, our results indicate that, in healthy overweight men, the type of protein in a high-fat meal interplays with fatty acid oxidation with a differential accumulation of incomplete oxidation products. A high-fat meal containing WHE, but not CAS, resulted in this outpacing of the tricarboxylic acid cycle. This study was registered at clinicaltrials.gov as NCT00931151.

Metabolic adaptations to HFHS overfeeding: how whole body and tissues postprandial metabolic flexibility adapt in Yucatan mini-pigs.

PURPOSE: In the present study, we aimed to metabolically characterize the postprandial adaptations of the major tissues involved in energy, lipids and amino acids metabolisms in mini-pigs. METHOD: Mini-pigs were fed on high-fat-high-sucrose (HFHS) diet for 2 months and several tissues explored for metabolic analyses. Further, the urine metabolome was followed over the time to picture the metabolic adaptations occurring at the whole body level following overfeeding. RESULTS: After 2 months of HFHS consumption, mini-pigs displayed an obese phenotype characterized by high circulating insulin, triglycerides and cholesterol levels. At the tissue level, a general (muscle, adipose tissue, intestine) reduction in the capacity to phosphorylate glucose was observed. This was also supported by the enhanced hepatic gluconeogenesis potential, despite the concomitant normoglycaemia, suggesting that the high circulating insulin levels would be enough to maintain glucose homoeostasis. The HFHS feeding also resulted in a reduced capacity of two other pathways: the de novo lipogenesis, and the branched-chain amino acids transamination. Finally, the follow-up of the urine metabolome over the time allowed determining breaking points in the metabolic trajectory of the animals. CONCLUSIONS: Several features confirmed the pertinence of the animal model, including increased body weight, adiposity and porcine obesity index. At the metabolic level, we observed a perturbed glucose and amino acid metabolism, known to be related to the onset of the obesity. The urine metabolome analyses revealed several metabolic pathways potentially involved in the obesity onset, including TCA (citrate, pantothenic acid), amino acids catabolism (cysteine, threonine, leucine).

Impact of medication on protein and amino acid metabolism in the elderly: the sulfur amino acid and paracetamol case.

The optimisation of nutritional support for the growing number of older individuals does not usually take into account medication. Paracetamol (acetaminophen; APAP) is the first intention treatment of chronic pain that is highly prevalent and persistent in the elderly. Detoxification of APAP occurs in the liver and utilises sulfate and glutathione (GSH), both of which are issued from cysteine (Cys), a conditionally indispensable amino acid. The detoxification-induced siphoning of Cys could reduce the availability of Cys for skeletal muscle. Consequently, APAP could worsen sarcopenia, an important component of the frailty syndrome leading to dependency. The present review provides the rationale for the potential pro-sarcopenic effect of APAP then recent results concerning the effect of chronic APAP treatment on muscle mass and metabolism are discussed. The principal findings are that chronic treatments with doses of APAP comparable with the maximum posology for humans can increase the requirement for sulfur amino acids (SAA), reduce Cys availability for muscle, reduce muscle protein synthesis and aggravate sarcopenia in animals. One clinical study is in favour of an enhanced SAA requirement in the older individual under chronic treatment with APAP. Few clinical studies investigated the effect of chronic treatment with APAP combined with exercise, in nutritional conditions that probably did not affect Cys and GSH homeostasis. Whether APAP can aggravate sarcopenia in older individuals with low protein intake remains to be tested. If true, nutritional strategies based on enhancing Cys supply could be of prime interest to cut down the pro-sarcopenic effect of chronic treatment with APAP.

Glucagon's effect on liver protein metabolism in vivo.

The postprandial state is characterized by a storage of nutrients in the liver, muscle, and adipose tissue for later utilization. In the case of a protein-rich meal, amino acids (AA) stimulate glucagon secretion by the α-cell. The aim of the present study was to determine the impact of the rise in glucagon on AA metabolism, particularly in the liver. We used a conscious catheterized dog model to recreate a postprandial condition using a pancreatic clamp. Portal infusions of glucose, AA, and insulin were used to achieve postprandial levels, while portal glucagon infusion was either maintained at the basal level or increased by three-fold. The high glucagon infusion reduced the increase in arterial AA concentrations compared with the basal glucagon level (-23%, P < 0.05). In the presence of high glucagon, liver AA metabolism shifted toward a more catabolic state with less protein synthesis (-36%) and increased urea production (+52%). Net hepatic glucose uptake was reduced modestly (-35%), and AA were preferentially used in gluconeogenesis, leading to lower glycogen synthesis (-54%). The phosphorylation of AMPK was increased by the high glucagon infusion (+40%), and this could be responsible for increasing the expression of genes related to pathways producing energy and lowering those involved in energy consumption. In conclusion, the rise in glucagon associated with a protein-rich meal promotes a catabolic utilization of AA in the liver, thereby, opposing the storage of AA in proteins.

Dietary proteins and amino acids in the control of the muscle mass during immobilization and aging: role of the MPS response.

Dietary proteins/essential amino acids (EAAs) are nutrients with anabolic properties that may increase muscle mass or attenuate muscle loss during immobilization and aging via the stimulation of muscle protein synthesis (MPS). An EAA's anabolic threshold, capable to maximize the stimulation of MPS has been hypothesized, but during certain conditions associated with muscle loss, this anabolic threshold seems to increase which reduces the efficacy of dietary EAAs to stimulate MPS. Preliminary studies have demonstrated that acute ingestion of dietary proteins/EAA (with a sufficient amount of leucine) was capable to restore the postprandial MPS during bed rest, immobilization or aging; however, whether these improvements translate into chronic increases (or attenuates loss) of muscle mass is equivocal. For example, although free leucine supplementation acutely increases MPS and muscle mass in some chronic studies, other studies have reported no increases in muscle mass following chronic leucine supplementation. In contrast, chronically increasing leucine intake via the consumption of an overall increase in dietary protein appears to be the most effective dietary intervention toward increasing or attenuating lean mass during aging; however, more research investigating the optimal dose and timing of protein ingestion is necessary. Several studies have demonstrated that decreases in postprandial MPS as a result of increased circulating oxidative and inflammatory are more responsible than muscle protein breakdown for the decreases in muscle mass during disuse and health aging. Therefore, nutritional interventions that reduce oxidation or inflammation in conjunction with higher protein intakes that overcome the anabolic resistance may enhance the MPS response to feeding and either increase muscle mass or attenuate loss. In preliminary studies, antioxidant vitamins and amino acids with antioxidant or anti-inflammatory properties show potential to restore the anabolic response associated with protein ingestion. More research, however, is required to investigate if these nutrients translate to increases in MPS and, ultimately, increased lean mass in aging humans. The purpose of the present review is to discuss the role of protein/EAA intake to enhance postprandial MPS during conditions associated with muscle loss, and bring new perspectives and challenges associated nutritional interventions aimed to optimize the anabolic effects of dietary protein/EAAs ingestion.

Dairy products and inflammation: A review of the clinical evidence.

Inflammation is a major biological process regulating the interaction between organisms and the environment, including the diet. Because of the increase in chronic inflammatory diseases, and in light of the immune-regulatory properties of breastfeeding, the ability of dairy products to modulate inflammatory processes in humans is an important but unresolved issue. Here, we report a systematic review of 52 clinical trials investigating inflammatory markers in relation to the consumption of dairy products. An inflammatory score (IS) was defined to quantitatively evaluate this interaction. The IS was significantly positive for the entire data set, indicating an anti-inflammatory activity in humans. When the subjects were stratified according to their health status, the IS was strongly indicative of an anti-inflammatory activity in subjects with metabolic disorders and of a pro-inflammatory activity in subjects allergic to bovine milk. Stratifying the data by product categories associated both low-fat and high-fat products, as well as fermented products, with an anti-inflammatory activity. Remarkably, the literature is characterized by a large gap in knowledge on bioavailability of bioactive nutrients. Future research should thus better combine food and nutritional sciences to adequately follow the fate of these nutrients along the gastrointestinal and metabolic axes.

Dietary supplementation with cysteine prevents adverse metabolic outcomes of repeated cures with paracetamol in old rats.

Cysteine (Cys), a conditionally indispensable amino acid, is required for the detoxification of paracetamol (acetaminophen, N-acetyl-para-aminophenol, 4-hydroxy-acetanilide, APAP), a drug of widespread use in older persons. We recently reported that repeated APAP cures could worsen sarcopenia in old rats, likely to be due to the impairment of Cys/GSH homoeostasis. The aim of the study was to evaluate whether a dietary Cys supplementation during APAP cures could improve Cys/GSH homoeostasis and thus preserve skeletal muscle. Male 21·5-month-old Wistar rats received three 2-week-long cures of APAP (1 % of diet) alone or with extra Cys (0·5 % of diet), intercalated with washout periods of 2 weeks (APAP and APAP-Cys groups, respectively). They were compared with untreated control rats (CT group). CT and APAP-Cys groups were pair-fed to the APAP group. Dietary Cys supplementation was efficient to prevent increase in liver mass (P<0·0001), decrease in liver GSH (P<0·0001), increase in blood GSH concentration (P<0·0001), and to some extent, decrease in plasma free Cys concentration (P<0·05), all induced by repeated APAP cures. The addition of Cys to APAP cures decreased plasma alanine transaminase (P<0·05), the fractional synthesis rate of liver proteins (P<0·01), and increased masses of extensor digitorum longus (P<0·01), and soleus (P<0·05), compared with the APAP group. Cys supplementation prevented alteration in Cys/GSH homoeostasis and increased some muscle masses in old rats under repeated cures with a non-toxic dose of APAP.

Similarities and interactions between the ageing process and high chronic intake of added sugars.

In our societies, the proportions of elderly people and of obese individuals are increasing. Both factors are associated with high health-related costs. During obesity, many authors suggest that it is a high chronic intake of added sugars (HCIAS) that triggers the shift towards pathology. However, the majority of studies were performed in young subjects and only a few were interested in the interaction with the ageing process. Our purpose was to discuss the metabolic effects of HCIAS, compare with the effects of ageing, and evaluate how deleterious the combined action of HCIAS and ageing could be. This effect of HCIAS seems mediated by fructose, targeting the liver first, which may lead to all subsequent metabolic alterations. The first basic alterations induced by fructose are increased oxidative stress, protein glycation, inflammation, dyslipidaemia and insulin resistance. These alterations are also present during the ageing process, and are closely related to each other, one leading to the other. These basic alterations are also involved in more complex syndromes, which are also favoured by HCIAS, and present during ageing. These include non-alcoholic fatty liver disease, hypertension, neurodegenerative diseases, sarcopenia and osteoporosis. Cumulative effects of ageing and HCIAS have been seldom tested and may not always be strictly additive. Data also suggest that some of the metabolic alterations that are more prevalent during ageing could be related more with nutritional habits than to intrinsic ageing. In conclusion, it is clear that HCIAS interacts with the ageing process, accelerates the accumulation of metabolic alterations, and that it should be avoided.

Time Course of Molecular and Metabolic Events in the Development of Insulin Resistance in Fructose-Fed Rats.

We aimed to determine the time-course of metabolic changes related to the early onset of insulin resistance (IR), trying to evidence breaking points preceding the appearance of the clinical IR phenotype. The model chosen was the fructose (FRU)-fed rat compared to controls fed with starch. We focused on the hepatic metabolism after 0, 5, 12, 30, or 45 days of FRU intake. The hepatic molecular metabolic changes followed indeed a multistep trajectory rather than a continuous progression. After 5 d of FRU feeding, we observed deep modifications in the hepatic metabolism, driven by the induction of lipogenic genes and important glycogen depletion. Thereafter, a steady-state period between days 12 and 30 was observed, characterized by a switch from carbohydrate to lipid utilization at the hepatic level and increased insulin levels aiming at alleviating lipid accumulation and hyperglycemia, respectively. The FRU-fed animals were only clinically IR at day 45 (altered homeostasis model assessment-estimated insulin resistance and muscle glucose transport). Furthermore, the urine metabolome revealed even earlier metabolic trajectory changes that precede the hepatic alterations. We identified several candidate metabolites linked to the tryptophan-nicotinamide metabolism and the installation of fasting hyperglycemia that suggest a role of this metabolic pathway on the development of the IR phenotype in the FRU-fed rats.

Long-term dietary supplementation with cystathionine improves tissue glutathione in ageing rats.

BACKGROUND: Ageing is associated with decrease in tissue glutathione that can be reduced by food fortification with the amino acid cysteine. However, cysteine is not stable in solution and generates bad taste. Cystathionine, the direct precursor of cysteine, could be a valuable alternative. AIMS: This study aimed to determine whether long-term dietary supplementation with cystathionine induces an increase in glutathione pools. METHODS: Aged rats (20.5-month-old) were fed ad libitum during 29 weeks with either a cystathionine-supplemented diet (7.3 g/kg, n = 90 rats) or a control iso-nitrogenous alanine-supplemented diet (2.9 g/kg, n = 90 rats). RESULTS: Cystathionine was detected in the plasma of the cystathionine-supplemented rats but not in the control alanine-supplemented rats. Cystathionine increased glutathione concentrations in liver, small intestine and gastrocnemius muscle (P < 0.03). No adverse effect was observed. CONCLUSION: Cystathionine supplementation being able to increase moderately glutathione in healthy old rats could be considered as a candidate for nutritional supports aiming to revert the stronger glutathione depletions occurring in unhealthy elderly.

Slight chronic elevation of C-reactive protein is associated with lower aerobic fitness but does not impair meal-induced stimulation of muscle protein metabolism in healthy old men.

Ageing impairs the muscle anabolic effect of food intake, which may explain muscle loss and an increased risk of sarcopenia. Ageing is also associated with low grade inflammation (LGI), which has been negatively correlated with muscle mass and strength. In rodents, the muscle anabolic resistance observed during ageing and sarcopenia has been ascribed to the development of the LGI. We aimed to investigate this relationship in humans. We studied protein metabolism and physical fitness in healthy elderly volunteers with slight chronic C-reactive protein. Two groups of healthy elderly volunteers were selected on the presence (or not) of a chronic, slight, elevation of CRP (Control: <1; CRP+: >2 mg l(-1) and <10 mg l(-1) , for 2 months). Body composition, short performance battery test, aerobic fitness and muscle strength were assessed. Whole body and muscle protein metabolism and the splanchnic extraction of amino acids were assessed using [(13) C]leucine and [(2) H]leucine infusion. The anabolic effect of food intake was measured by studying the volunteers both at the post-absorptive and post-prandial states. Slight chronic CRP elevation resulted in neither an alteration of whole body, nor skeletal muscle protein metabolism at both the post-absorptive and the post-prandial states. However, CRP+ presented a reduction of physical fitness, increased abdominal fat mass and post-prandial insulin resistance. Plasma cytokines (interleukin-1, interleukin-6, tumour necrosis factor α) and markers of endothelial inflammation (intercellular adhesion molecule, vascular cell adhesion molecule, selectins) were similar between groups. An isolated elevated CRP in healthy older population does not indicate an impaired skeletal muscle anabolism after food intake, nor an increased risk of skeletal muscle wasting. We propose that a broader picture of LGI (notably with elevated pro-inflammatory cytokines) is required to impact muscle metabolism and mass. However, an isolated chronic CRP elevation could predict a decrease in aerobic fitness and insulin resistance installation in elderly individuals.

Chronic Intake of Sucrose Accelerates Sarcopenia in Older Male Rats through Alterations in Insulin Sensitivity and Muscle Protein Synthesis.

BACKGROUND: Today, high chronic intake of added sugars is frequent, which leads to inflammation, oxidative stress, and insulin resistance. These 3 factors could reduce meal-induced stimulation of muscle protein synthesis and thus aggravate the age-related loss of muscle mass (sarcopenia). OBJECTIVES: Our aims were to determine if added sugars could accelerate sarcopenia and to assess the capacity of antioxidants and anti-inflammatory agents to prevent this. METHODS: For 5 mo, 16-mo-old male rats were starch fed (13% sucrose and 49% wheat starch diet) or sucrose fed (62% sucrose and 0% wheat starch diet) with or without rutin (5 g/kg diet), vitamin E (4 times), vitamin A (2 times), vitamin D (5 times), selenium (10 times), and zinc (+44%) (R) supplementation. We measured the evolution of body composition and inflammation, plasma insulin-like growth factor 1 (IGF-I) concentration and total antioxidant status, insulin sensitivity (oral-glucose-tolerance test), muscle weight, superoxide dismutase activity, glutathione concentration, and in vivo protein synthesis rates. RESULTS: Sucrose-fed rats lost significantly more lean body mass (-8.1% vs. -5.4%, respectively) and retained more fat mass (+0.2% vs. -33%, respectively) than starch-fed rats. Final muscle mass was 11% higher in starch-fed rats than in sucrose-fed rats. Sucrose had little effect on inflammation, oxidative stress, and plasma IGF-I concentration but reduced the insulin sensitivity index (divided by 2). Meal-induced stimulation of muscle protein synthesis was significantly lower in sucrose-fed rats (+7.3%) than in starch-fed rats (+22%). R supplementation slightly but significantly reduced oxidative stress and increased muscle protein concentration (+4%) but did not restore postprandial stimulation of muscle protein synthesis. CONCLUSIONS: High chronic sucrose intake accelerates sarcopenia in older male rats through an alteration of postprandial stimulation of muscle protein synthesis. This effect could be explained by a decrease of insulin sensitivity rather than by changes in plasma IGF-I, inflammation, and/or oxidative stress.

Nutritional strategies to counteract muscle atrophy caused by disuse and to improve recovery.

Periods of immobilisation are often associated with pathologies and/or ageing. These periods of muscle disuse induce muscle atrophy which could worsen the pathology or elderly frailty. If muscle mass loss has positive effects in the short term, a sustained/uncontrolled muscle mass loss is deleterious for health. Muscle mass recovery following immobilisation-induced atrophy could be critical, particularly when it is uncompleted as observed during ageing. Exercise, the best way to recover muscle mass, is not always applicable. So, other approaches such as nutritional strategies are needed to limit muscle wasting and to improve muscle mass recovery in such situations. The present review discusses mechanisms involved in muscle atrophy following disuse and during recovery and emphasises the effect of age in these mechanisms. In addition, the efficiency of nutritional strategies proposed to limit muscle mass loss during disuse and to improve protein gain during recovery (leucine supplementation, whey proteins, antioxidants and anti-inflammatory compounds, energy intake) is also discussed.

Development of a protein food based on texturized wheat proteins, with high protein digestibility and improved lysine content.

The development of plant-based protein foods may facilitate the decrease in animal product consumption in western countries. Wheat proteins, as a starch coproduct, are available in large amounts and are good candidates for this development. We investigated the effect of a new texturing process on wheat protein digestibility and implemented strategies aimed at enhancing the lysine content of the product developed. Protein true ileal digestibility (TID) was determined in minipigs. In a preliminary experiment, the TID of wheat protein (WP), texturized wheat protein (TWP), TWP enriched with free lysine (TWP-L), or with chickpea flour (TWP-CP) was measured and compared to beef meat proteins. In the main experiment, minipigs (n = 6) were fed a dish (blanquette type) containing 40 g of protein in the form of TWP-CP, TWP-CP enriched with free lysine TWP-CP+L, chicken filet, or texturized soy, together with quinoa (18.5 g of protein) in order to improve meal supply of lysine. Wheat protein texturing did not affect total amino acid TID (96.8 % for TWP vs 95.3 % for WP), which was not different from that of beef meat (95.8 %). Chickpea addition did not affect protein TID (96.5 % for TWP-CP vs 96.8 % for TWP). The Digestible Indispensable Amino Acid Score for adults of the dish combining TWP-CP+L with quinoa was 91, whereas it was 110 and 111 for the dishes containing chicken filet or texturized soy. The above results show that, by optimizing lysine content through the formulation of the product, wheat protein texturization can enable the development of protein-rich products of nutritional quality compatible with quality protein intake in the context of a complete meal.

Contrarily to whey and high protein diets, dietary free leucine supplementation cannot reverse the lack of recovery of muscle mass after prolonged immobilization during ageing.

During ageing, immobilization periods increase and are partially responsible of sarcopaenia by inducing a muscle atrophy which is hardly recovered from. Immobilization-induced atrophy is due to an increase of muscle apoptotic and proteolytic processes and decreased protein synthesis. Moreover, previous data suggested that the lack of muscle mass recovery might be due to a defect in protein synthesis response during rehabilitation. This study was conducted to explore protein synthesis during reloading and leucine supplementation effect as a nutritional strategy for muscle recovery. Old rats (22­24 months old) were subjected to unilateral hindlimb casting for 8 days (I8) and allowed to recover for 10­40 days (R10­R40). They were fed a casein (±leucine) diet during the recovery. Immobilized gastrocnemius muscles atrophied by 20%, and did not recover even at R40. Amount of polyubiquitinated conjugates and chymotrypsin- and trypsin-like activities of the 26S proteasome increased. These changes paralleled an 'anabolic resistance' of the protein synthesis at the postprandial state (decrease of protein synthesis, P-S6 and P-4E-BP1). During the recovery, proteasome activities remained elevated until R10 before complete normalization and protein synthesis was slightly increased. With free leucine supplementation during recovery, if proteasome activities were normalized earlier and protein synthesis was higher during the whole recovery, it nevertheless failed in muscle mass gain. This discrepancy could be due to a 'desynchronization' between the leucine signal and the availability of amino acids coming from casein digestion. Thus, when supplemented with leucine-rich proteins (i.e. whey) and high protein diets, animals partially recovered the muscle mass loss.

Portal glucose delivery stimulates muscle but not liver protein metabolism.

Portal vein glucose delivery (the portal glucose signal) stimulates glucose uptake and glycogen storage by the liver, whereas portal amino acid (AA) delivery (the portal AA signal) induces an increase in protein synthesis by the liver. During a meal, both signals coexist and may interact. In this study, we compared the protein synthesis rates in the liver and muscle in response to portal or peripheral glucose infusion during intraportal infusion of a complete AA mixture. Dogs were surgically prepared with hepatic sampling catheters and flow probes. After a 42-h fast, they underwent a 3-h hyperinsulinemic (4× basal) hyperglucagonemic (3× basal) hyperglycemic (≈160 mg/dl) hyperaminoacidemic (hepatic load 1.5× basal; delivered intraportally) clamp (postprandial conditions). Glucose was infused either via a peripheral (PeG; n = 7) or the portal vein (PoG; n = 8). Protein synthesis was assessed with a primed, continuous [(14)C]leucine infusion. Net hepatic glucose uptake was stimulated by portal glucose infusion (+1 mg·kg(-1)·min(-1), P < 0.05) as expected, but hepatic fractional AA extraction and hepatic protein synthesis did not differ between groups. There was a lower arterial AA concentration in the PoG group (-19%, P < 0.05) and a significant stimulation (+30%) of muscle protein synthesis associated with increased expression of LAT1 and ASCT2 AA transporters and p70S6 phosphorylation. Concomitant portal glucose and AA delivery enhances skeletal muscle protein synthesis compared with peripheral glucose and portal AA delivery. These data suggest that enteral nutrition support may have an advantage over parenteral nutrition in stimulating muscle protein synthesis.