Skeletal Muscle Proteome Modifications following Antibiotic-Induced Microbial Disturbances in Cancer Cachexia.

Cancer cachexia is an involuntary loss of body weight, mostly of skeletal muscle. Previous research favors the existence of a microbiota-muscle crosstalk, so the aim of the study was to evaluate the impact of microbiota alterations induced by antibiotics on skeletal muscle proteins expression. Skeletal muscle proteome changes were investigated in control (CT) or C26 cachectic mice (C26) with or without antibiotic treatment (CT-ATB or C26-ATB, n = 8 per group). Muscle protein extracts were divided into a sarcoplasmic and myofibrillar fraction and then underwent label-free liquid chromatography separation, mass spectrometry analysis, Mascot protein identification, and METASCAPE platform data analysis. In C26 mice, the atrogen mafbx expression was 353% higher than CT mice and 42.3% higher than C26-ATB mice. No effect on the muscle protein synthesis was observed. Proteomic analyses revealed a strong effect of antibiotics on skeletal muscle proteome outside of cachexia, with adaptative processes involved in protein folding, growth, energy metabolism, and muscle contraction. In C26-ATB mice, proteome adaptations observed in CT-ATB mice were blunted. Differentially expressed proteins were involved in other processes like glucose metabolism, oxidative stress response, and proteolysis. This study confirms the existence of a microbiota-muscle axis, with a muscle response after antibiotics that varies depending on whether cachexia is present.

Protein and amino acids in obesity: friends or foes?

PURPOSE OF REVIEW: Nutritional interventions using protein and amino acids in obesity are popular therapeutical strategies to limit obesity development. However, the effects of dietary protein intake and amino acid metabolic alterations involved in obesity pathophysiology have not been completely unravelled. Significant recent studies have brought to light new findings in these areas, which are the primary focus of this review. RECENT FINDINGS: We describe the effects of protein intake on weight regain prevention, the influence on gut microbiota, the response to low-protein highly processed foods, and the contrasting impacts of a high-protein diet on adults and children. We also explore newly discovered correlations between amino acids, liver fat accumulation, and the dysregulation of the liver-pancreas axis due to alterations in amino acid levels in the context of obesity. Lastly, we consider branched-chain amino acids, along with glycine and tryptophan, as significant biomarkers during periods of positive or negative energy balance. SUMMARY: Interventions using dietary protein in obesity may be useful, especially during energy restriction but also in sarcopenic obesity. Furthermore, metabolic profiles that encompass alterations in certain amino acids can provide valuable insights into the metabolic condition of patients with obesity, particularly in relation to insulin resistance and the risk of developing type 2 diabetes.

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.

A new clinically-relevant rat model of letrozole-induced chronic nociceptive disorders.

Among postmenopausal women with estrogen receptor-positive breast cancer, more than 80% receive hormone therapy including aromatase inhibitors (AIs). Half of them develop chronic arthralgia - characterized by symmetric articular pain, carpal tunnel syndrome, morning stiffness, myalgia and a decrease in grip strength - which is associated with treatment discontinuation. Only a few animal studies have linked AI treatment to nociception, and none to arthralgia. Thus, we developed a new chronic AI-induced nociceptive disorder model mimicking clinical symptoms induced by AIs, using subcutaneous letrozole pellets in ovariectomized (OVX) rats. Following plasma letrozole dosage at the end of the experiment (day 73), only rats with at least 90 ng/ml of letrozole were considered significantly exposed to letrozole (OVX + high LTZ group), whereas treated animals with less than 90 ng/ml were pooled in the OVX + low LTZ group. Chronic nociceptive disorder set in rapidly and was maintained for more than 70 days in the OVX + high LTZ group. Furthermore, OVX + high LTZ rats saw no alteration in locomotion, myalgia or experimental anxiety during this period. Bone parameters of the femora were significantly altered in all OVX rats compared to Sham+vehicle pellet. A mechanistic analysis focused on TRPA1, receptor suspected to mediate AI-evoked pain, and showed no modification in its expression in the DRG. This new long-lasting chronic rat model, efficiently reproduces the symptoms of AI-induced nociceptive disorder affecting patients' daily activities and quality-of-life. It should help to study the pathophysiology of this disorder and to promote the development of new therapeutic strategies.

Protein, amino acids and obesity treatment.

Dietary proteins have been used for years to treat obesity. Body weight loss is beneficial when it concerns fat mass, but loss of fat free mass - especially muscle might be detrimental. This occurs because protein breakdown predominates over synthesis, thus administering anabolic dietary compounds like proteins might counter fat free mass loss while allowing for fat mass loss.Indeed, varying the quantity of proteins will decrease muscle anabolic response and increase hyperphagia in rodents fed a low protein diet; but it will favor lean mass maintenance and promote satiety, in certain age groups of humans fed a high protein diet. Beyond protein quantity, protein source is an important metabolic regulator: whey protein and plant based diets exercize favorable effects on the risk of developing obesity, body composition, metabolic parameters or fat free mass preservation of obese patients. Specific amino-acids like branched chain amino acids (BCAA), methionine, tryptophan and its metabolites, and glutamate can also positively influence parameters and complications of obesity especially in rodent models, with less studies translating this in humans.Tuning the quality and quantity of proteins or even specific amino-acids can thus be seen as a potential therapeutic intervention on the body composition, metabolic syndrome parameters and appetite regulation of obese patients. Since these effects vary across age groups and much of the data comes from murine models, long-term prospective studies modulating proteins and amino acids in the human diet are needed.

Nutritional evaluation of mixed wheat-faba bean pasta in growing rats: impact of protein source and drying temperature on protein digestibility and retention.

This study aimed to evaluate the nutritional value of pasta enriched with legume or wheat gluten proteins and dried at varying temperature. A total of four isonitrogenous experimental diets were produced using gluten powder/wheat semolina (6/94, g/g) pasta and faba bean flour/wheat semolina (35/65, g/g) pasta dried at either 55°C (GLT and FLT, respectively) or 90°C (FVHT and GVHT, respectively). Experimental diets were fed to ten 1-month-old Wistar rats (body weight=176 (sem 15) g) for 21 d. Growth and nutritional, metabolic and inflammatory markers were measured and compared with an isonitrogenous casein diet (CD). The enrichment with faba bean increased the lysine, threonine and branched amino acids by 97, 23 and 10 %, respectively. Protein utilisation also increased by 75 % (P<0·01) in FLT in comparison to GLT diet, without any effect on the corrected faecal digestibility (P>0·05). Faba bean pasta diets' corrected protein digestibility and utilisation was only 3·5 and 9 %, respectively, lower than the CD. Growth rate, blood composition and muscle weights were not generally different with faba bean pasta diets compared with CD. Corrected protein digestibility was 3 % lower in GVHT than GLT, which may be associated with greater carboxymethyllysine. This study in growing rats clearly indicates improvement in growth performance of rats fed legume-enriched pasta diet compared with rats fed gluten-wheat pasta diet, regardless of pasta drying temperature. This means faba bean flour can be used to improve the protein quality and quantity of pasta.

Fast digestive proteins and sarcopenia of aging.

PURPOSE OF REVIEW: The speed of dietary protein digestion influences postprandial amino acid availability which is crucial for improving altered anabolic response of skeletal muscle one feature of sarcopenia during aging. RECENT FINDINGS: By analogy with carbohydrate and in reference to their absorption rate, dietary proteins can be classified as 'fast' or 'slow' proteins depending on matrix food structure and technological processes, which can influence amino acids availability and their subsequent metabolic actions. 'Fast' digestive proteins have been shown to stimulate muscle protein synthesis and to improve muscle function in several recent studies involving older patients. These new aspects may be applied for improving health through preservation or restoration of muscle protein mass and function in clinical situations (obesity, rheumatoid arthritis and cancer cachexia). SUMMARY: Using fast digestive proteins is of major interest to overcome 'anabolic resistance' of aging for limiting sarcopenia. Fast proteins' action on muscle anabolism may be stimulated by other nutrients like vitamin D or omega 3 fatty acids or by combination with exercise. The beneficial impact of the 'fast' protein concept beyond the amount of dietary protein on muscle preservation is a promising therapeutic perspective to improve mobility and quality of life of older patients affected with chronic disease.

Exercise training and return to a well-balanced diet activate the neuregulin 1/ErbB pathway in skeletal muscle of obese rats.

KEY POINTS: Some studies suggest that neuregulin 1 (NRG1) could be involved in the regulation of skeletal muscle energy metabolism in rodents. Here we assessed whether unbalanced diet is associated with alterations of the NRG1 signalling pathway and whether exercise and diet might restore NRG1 signalling in skeletal muscle of obese rats. We show that diet-induced obesity does not impair NRG1 signalling in rat skeletal muscle. We also report that endurance training and a well-balanced diet activate the NRG1 signalling in skeletal muscle of obese rats, possibly via a new mechanism mediated by the protease ADAM17. These results suggest that some beneficial effects of physical activity and diet in obese rats could be partly explained by stimulation of the NRG1 signalling pathway. ABSTRACT: Some studies suggest that the signalling pathway of neuregulin 1 (NRG1), a protein involved in the regulation of skeletal muscle metabolism, could be altered by nutritional and exercise interventions. We hypothesized that diet-induced obesity could lead to alterations of the NRG1 signalling pathway and that chronic exercise could improve NRG1 signalling in rat skeletal muscle. To test this hypothesis, male Wistar rats received a high fat/high sucrose (HF/HS) diet for 16 weeks. At the end of this period, NRG1 and ErbB expression/activity in skeletal muscle was assessed. The obese rats then continued the HF/HS diet or were switched to a well-balanced diet. Moreover, in both groups, half of the animals also performed low intensity treadmill exercise training. After another 8 weeks, NRG1 and ErbB expression/activity in skeletal muscle were tested again. The 16 week HF/HS diet induced obesity, but did not significantly affect the NRG1/ErbB signalling pathway in rat skeletal muscle. Conversely, after the switch to a well-balanced diet, NRG1 cleavage ratio and ErbB4 amount were increased. Chronic exercise training also promoted NRG1 cleavage, resulting in increased ErbB4 phosphorylation. This result was associated with increased protein expression and phosphorylation ratio of the metalloprotease ADAM17, which is involved in NRG1 shedding. Similarly, in vitro stretch-induced activation of ADAM17 in rat myoblasts induced NRG1 cleavage and ErbB4 activation. These results show that low intensity endurance training and well-balanced diet activate the NRG1-ErbB4 pathway, possibly via the metalloprotease ADAM17, in skeletal muscle of diet-induced obese rats.

Sarcopenia and Sarcopenic Obesity and Mortality Among Older People.

Importance: Sarcopenia and obesity are 2 global concerns associated with adverse health outcomes in older people. Evidence on the population-based prevalence of the combination of sarcopenia with obesity (sarcopenic obesity [SO]) and its association with mortality are still limited. Objective: To investigate the prevalence of sarcopenia and SO and their association with all-cause mortality. Design, Setting, and Participants: This large-scale, population-based cohort study assessed participants from the Rotterdam Study from March 1, 2009, to June 1, 2014. Associations of sarcopenia and SO with all-cause mortality were studied using Kaplan-Meier curves, Cox proportional hazards regression, and accelerated failure time models fitted for sex, age, and body mass index (BMI). Data analysis was performed from January 1 to April 1, 2023. Exposures: The prevalence of sarcopenia and SO, measured based on handgrip strength and body composition (BC) (dual-energy x-ray absorptiometry) as recommended by current consensus criteria, with probable sarcopenia defined as having low handgrip strength and confirmed sarcopenia and SO defined as altered BC (high fat percentage and/or low appendicular skeletal muscle index) in addition to low handgrip strength. Main Outcome and Measure: The primary outcome was all-cause mortality, collected using linked mortality data from general practitioners and the central municipal records, until October 2022. Results: In the total population of 5888 participants (mean [SD] age, 69.5 [9.1] years; mean [SD] BMI, 27.5 [4.3]; 3343 [56.8%] female), 653 (11.1%; 95% CI, 10.3%-11.9%) had probable sarcopenia and 127 (2.2%; 95% CI, 1.8%-2.6%) had confirmed sarcopenia. Sarcopenic obesity with 1 altered component of BC was present in 295 participants (5.0%; 95% CI, 4.4%-5.6%) and with 2 altered components in 44 participants (0.8%; 95% CI, 0.6%-1.0%). An increased risk of all-cause mortality was observed in participants with probable sarcopenia (hazard ratio [HR], 1.29; 95% CI, 1.14-1.47) and confirmed sarcopenia (HR, 1.93; 95% CI, 1.53-2.43). Participants with SO plus 1 altered component of BC (HR, 1.94; 95% CI, 1.60-2.33]) or 2 altered components of BC (HR, 2.84; 95% CI, 1.97-4.11) had a higher risk of mortality than those without SO. Similar results for SO were obtained for participants with a BMI of 27 or greater. Conclusions and Relevance: In this study, sarcopenia and SO were found to be prevalent phenotypes in older people and were associated with all-cause mortality. Additional alterations of BC amplified this risk independently of age, sex, and BMI. The use of low muscle strength as a first step of both diagnoses may allow for early identification of individuals at risk for premature mortality.

Associating Inulin with a Pea Protein Improves Fast-Twitch Skeletal Muscle Mass and Muscle Mitochondrial Activities in Old Rats.

Aging is associated with a decline in muscle mass and function, leading to increased risk for mobility limitations and frailty. Dietary interventions incorporating specific nutrients, such as pea proteins or inulin, have shown promise in attenuating age-related muscle loss. This study aimed to investigate the effect of pea proteins given with inulin on skeletal muscle in old rats. Old male rats (20 months old) were randomly assigned to one of two diet groups for 16 weeks: a 'PEA' group receiving a pea-protein-based diet, or a 'PEA + INU' group receiving the same pea protein-based diet supplemented with inulin. Both groups showed significant postprandial stimulation of muscle p70 S6 kinase phosphorylation rate after consumption of pea proteins. However, the PEA + INU rats showed significant preservation of muscle mass with time together with decreased MuRF1 transcript levels. In addition, inulin specifically increased PGC1-α expression and key mitochondrial enzyme activities in the plantaris muscle of the old rats. These findings suggest that dietary supplementation with pea proteins in combination with inulin has the potential to attenuate age-related muscle loss. Further research is warranted to explore the underlying mechanisms and determine the optimal dosage and duration of intervention for potential translation to human studies.

Sarcopenic obesity research perspectives outlined by the sarcopenic obesity global leadership initiative (SOGLI) - Proceedings from the SOGLI consortium meeting in rome November 2022.

The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched the Sarcopenic Obesity Global Leadership Initiative (SOGLI) to reach expert consensus on a definition and diagnostic criteria for Sarcopenic Obesity (SO). The present paper describes the proceeding of the Sarcopenic Obesity Global Leadership Initiative (SOGLI) meeting that was held on November 25th and 26th, 2022 in Rome, Italy. This consortium involved the participation of 50 researchers from different geographic regions and countries. The document outlines an agenda advocated by the SOGLI expert panel regarding the pathophysiology, screening, diagnosis, staging and treatment of SO that needs to be prioritized for future research in the field.

Time-course changes of muscle protein synthesis associated with obesity-induced lipotoxicity.

The object of the study was to investigate the sequential changes of protein synthesis in skeletal muscle during establishment of obesity, considering muscle typology. Adult Wistar rats were fed a standard diet for 16 weeks (C; n = 14), or a high-fat, high-sucrose diet for 16 (HF16; n = 14) or 24 weeks (HF24; n = 15). Body composition was measured using a dual-energy X-ray absorptiometry scanner. The fractional synthesis rates (FSRs) of muscle protein fractions were calculated in tibialis anterior (TA) and soleus muscles by incorporation of l-13C-valine in muscle protein. Muscle lipid and mitochondria contents were determined using histochemical analysis. Obesity occurred in an initial phase, from 1 to 16 weeks, with an increase in weight (P < 0.05), fat mass (P < 0.001), muscle mass (P < 0.001) and FSR in TA (actin: 5.3 ± 0.2 vs. 8.8 ± 0.5% day−1, C vs. HF16, P < 0.001) compared with standard diet. The second phase, from 16 to 24 weeks, was associated with a weight stabilization, a decrease in muscle mass (P < 0.05) and a decrease in FSR in TA (mitochondrial: 5.6 ± 0.2 vs. 4.2 ± 0.4% day−1, HF16 vs. HF24, P < 0.01) compared with HF16 group. Muscle lipid content was increased in TA in the second phase of obesity development (P < 0.001). Muscle mass, lipid infiltration and muscle protein synthesis were differently affected, depending on the stage of obesity development and muscle typology. Chronic lipid infiltration in glycolytic muscle is concomitant with a reduction of muscle protein synthesis, suggesting that muscle lipid infiltration in response to a high-fat diet is deleterious for the incorporation of amino acid in skeletal muscle proteins.

Impact of an obesogenic diet program on bone densitometry, micro architecture and metabolism in male rat.

BACKGROUND: The relationships between fat mass and bone tissue are complex and not fully elucidated. A high-fat/high-sucrose diet has been shown to induce harmful effects on bone micro architecture and bone biomechanics of rat. When such diet leads to obesity, it may induce an improvement of biomechanical bone parameters in rodent.Here, we examined the impact of a high-fat/high-sucrose diet on the body composition and its resulting effects on bone density and structure in male rats. Forty three Wistar rats aged 7 months were split into 3 groups: 1 sacrificed before diet (BD, n = 14); 1 subjected to 16 weeks of high-fat/high-sucrose diet (HF/HS, n = 14); 1 subjected to standard diet (Control, n = 15). Abdominal circumference and insulin sensitivity were measured and visceral fat mass was weighed. The bone mineral density (BMD) was analyzed at the whole body and tibia by densitometry. Microcomputed tomography and histomorphometric analysis were performed at L2 vertebrae and tibia to study the trabecular and cortical bone structures and the bone cell activities. Osteocalcin and CTX levels were performed to assess the relative balance of the bone formation and resorption. Differences between groups have been tested with an ANOVA with subsequent Scheffe post-hoc test. An ANCOVA with global mass and global fat as covariates was used to determine the potential implication of the resulting mechanical loading on bone. RESULTS: The HF/HS group had higher body mass, fat masses and abdominal circumference and developed an impaired glucose tolerance (p < 0.001). Whole body bone mass (p < 0.001) and BMD (p < 0.05) were higher in HF/HS group vs. Control group. The trabecular thickness at vertebrae and the cortical porosity of tibia were improved (p < 0.05) in HF/HS group. Bone formation was predominant in HF/HS group while an unbalance bone favoring bone resorption was observed in the controls. The HF/HS and Control groups had higher total and abdominal fat masses and altered bone parameters vs. BD group. CONCLUSIONS: The HF/HS diet had induced obesity and impaired glucose tolerance. These changes resulted in an improvement of quantitative, qualitative and metabolic bone parameters. The fat mass increase partly explained these observations.

Variability in Skeletal Muscle Protein Synthesis Rates in Critically Ill Patients.

(1) Background: Muscle protein synthesis in critically ill patients is, on average, normal despite dramatic muscle loss, but the variation is much larger than in controls. Here, we evaluate if this variation is due to 1) heterogeneity in synthesis rates, 2) morphological variation or infiltrating cells, or 3) heterogeneity in the synthesis of different protein fractions. (2) Methods: Muscle biopsies were taken from both legs of critically ill patients (n = 17). Mixed and mitochondrial protein synthesis rates and morphologies were evaluated in both legs. Synthesis rates of myosin and actin were determined in combined biopsies and compared with controls. (3) Results: Muscle protein synthesis rates had a large variability in the patients (1.4-10.8%/day). No differences in mixed and mitochondrial protein synthesis rates between both legs were observed. A microscopic examination revealed no morphological differences between the two legs or any infiltrating inflammatory cells. The synthesis rates for myosin were lower and for actin they were higher in the muscles of critically ill patients, compared with the controls. (4) Conclusions: The large variation in muscle protein synthesis rates in critically ill patients is not the result of heterogeneity in synthesis rates, nor due to infiltrating cells. There are differences in the synthesis rates of different proteins, but these do not explain the larger variations.

Peripheral Amino Acid Appearance Is Lower Following Plant Protein Fibre Products, Compared to Whey Protein and Fibre Ingestion, in Healthy Older Adults despite Optimised Amino Acid Profile.

Plant-based proteins are generally characterised by lower Indispensable Amino Acid (IAA) content, digestibility, and anabolic properties, compared to animal-based proteins. However, they are environmentally friendlier, and wider consumption is advocated. Older adults have higher dietary protein needs to prevent sarcopenia, a disease marked by an accelerated loss of muscle mass and function. Given the lower environmental footprint of plant-based proteins and the importance of optimising dietary protein quality among older adults, this paper aims to assess the net peripheral Amino Acid (AA) appearance after ingestion of three different plant protein and fibre (PPF) products, compared to whey protein with added fibre (WPF), in healthy older adults. In a randomised, single-blind, crossover design, nine healthy men and women aged ≥65 years consumed four test meals balanced in AA according to the FAO reference protein for humans, matched for leucine, to optimally stimulate muscle protein synthesis in older adults. A fasted blood sample was drawn at each visit before consuming the test meal, followed by postprandial arterialise blood sampling every 30 min for 3 h. The test meal was composed of a soup containing either WPF or PPF 1-3. The PPF blends comprised pea proteins with varying additional rice, pumpkin, soy, oat, and/or almond protein. PPF product ingestion resulted in a lower maximal increase of postprandial leucine concentration and the sum of branched-chain AA (BCAA) and IAA concentrations, compared to WPF, with no effect on their incremental area under the curve. Plasma methionine and cysteine, and to a lesser extent threonine, appearance were limited after consuming the PPF products, but not WPF. Despite equal leucine doses, the WPF induced greater postprandial insulin concentrations than the PPF products. In conclusion, the postprandial appearance of AA is highly dependent on the protein source in older adults, despite providing equivalent IAA levels and dietary fibre. Coupled with lower insulin concentrations, this could imply less anabolic potential. Further investigation is required to understand the applicability of plant-based proteins in healthy older adults.

Vitamin D status modulates mitochondrial oxidative capacities in skeletal muscle: role in sarcopenia.

Skeletal muscle mitochondrial function is the biggest component of whole-body energy output. Mitochondrial energy production during exercise is impaired in vitamin D-deficient subjects. In cultured myotubes, loss of vitamin D receptor (VDR) function decreases mitochondrial respiration rate and ATP production from oxidative phosphorylation. We aimed to examine the effects of vitamin D deficiency and supplementation on whole-body energy expenditure and muscle mitochondrial function in old rats, old mice, and human subjects. To gain further insight into the mechanisms involved, we used C2C12 and human muscle cells and transgenic mice with muscle-specific VDR tamoxifen-inducible deficiency. We observed that in vivo and in vitro vitamin D fluctuations changed mitochondrial biogenesis and oxidative activity in skeletal muscle. Vitamin D supplementation initiated in older people improved muscle mass and strength. We hypothesize that vitamin D supplementation is likely to help prevent not only sarcopenia but also sarcopenic obesity in vitamin D-deficient subjects.

Is protein metabolism changed with obesity?

PURPOSE OF REVIEW: Although it is well established that obesity is accompanied by various degrees of metabolic impairments especially in the regulation of carbohydrate and lipid metabolism, the influence of obesity on protein metabolism is not clearly understood. The purpose of this review is to present data describing the modification in protein metabolism that have been reported in the clinical setting of obesity. RECENT FINDINGS: Recent findings suggest that protein metabolism at the whole-body level is less sensitive to insulin action. Impairments in skeletal muscle protein synthesis rates in the postabsorptive state and in response to anabolic factors are reported in obese human. Finally, chronic excessive energy intake and increased adiposity in rats, without the appearance of other metabolic disturbances, do not induce any changes in tissue protein synthesis rates. SUMMARY: Body composition in obesity is characterized by elevated fat mass but also lean body mass which is considered either increased or decreased (in the case of sarcopenic obesity). Thus protein metabolism as reflected by changes in protein synthesis and breakdown might be modified in obese individuals but it is still largely debated. Only a few studies have investigated muscle protein kinetics during obesity and do not lead to the same conclusions prolonging the controversies. Indeed, obesity is associated with many metabolic disturbances which might constitute confounding factors differently affecting muscle protein metabolism.

Effect of fast dietary proteins on muscle protein synthesis rate and muscle strength in ad libitum-fed and energy-restricted old rats.

Sarcopenia is defined as age-related loss of muscle mass and strength. Energy restriction (ER) delays fibre loss by limiting the accumulated deleterious effects of reactive oxygen species on muscle. However, insufficient protein intake during ER might affect muscle mass and function. We hypothesised that ingestion of fast-digested proteins such as whey protein (WP) improves muscle protein synthesis and muscle strength in aged ER rats. The effect of WP or casein (CAS, slow protein) on muscle mass, protein synthesis and strength was evaluated in 21-month-old rats fed for 5 months either ad libitum (AL) or a 40 % protein and energy-restricted (PER) or 40 % AL-isonitrogenous ER diet. The nitrogen balance was reduced in PER-CAS rats only ( - 48 % v. AL-CAS). WP stimulated muscle protein synthesis rates compared with CAS in all groups (+21,+37 and +34 % in AL, PER and ER conditions, respectively). Muscle strength was higher in ER rats than in AL rats (+23 and +12 % for WP or CAS, respectively). Muscle performance tended to be greater in ER rats fed WP than in ER-CAS rats (P < 0·09). In conclusion, we observed that long-term ER combined with maintained protein intake had a beneficial impact on muscle protein synthesis rate and function during ageing.

Deleterious Effect of High-Fat Diet on Skeletal Muscle Performance Is Prevented by High-Protein Intake in Adult Rats but Not in Old Rats.

The phenotype of sarcopenic obesity is frequently associated with impaired muscle strength and performance. Ectopic lipid deposition may interfere with muscle anabolic response especially during aging. Evidence is scarce concerning the potential interplay among aging and nutrient imbalance on skeletal muscle functionality. The objective of the present study was to investigate the impact of protein intake in the context of an obesogenic diet on skeletal muscle functional properties and intramuscular lipid infiltration. Two groups of forty-two adult and thirty-seven old male Wistar rats were randomly divided into four groups: isocaloric standard diet (12% protein, 14% lipid, as ST12); isocaloric standard (high-protein) diet (25% protein, 14% lipid, ST25); hypercaloric high-fat (normal-protein) diet (12% protein, 45% lipid, HF12); and hypercaloric high-fat (high-protein) diet (25% protein, 45% lipid, HF25). The nutritional intervention lasted 10 weeks. Total body composition was measured through Echo-MRI. Lipids were extracted from tibialis anterior muscle and analyzed by gas-liquid chromatography. The functional properties of the plantarflexor muscles were evaluated in vivo on an isokinetic dynamometer. Maximal torque was assessed from the torque-frequency relationship in isometric condition and maximal power was evaluated from the torque-velocity relationship in concentric condition. In adult rats high-protein intake combined with high-fat diet determined a lower decrease in relative isometric torque, normalized to either FFM or body weight, compared with adult rats fed a high-fat normal-protein diet. High-fat diet was also detrimental to relative muscle power, as normalized to body weight, that decreased to a larger extent in adult rats fed a high-fat normal-protein diet than their counterparts fed a normal-fat, high-protein diet. The effect of high-fat diet observed in adults, with the enhanced protein intake (25%) conferring some kind of protection against the negative effects of HFD, may be linked to the reduced intramuscular fat in this group, which may have contributed to preserve, at least partly, the contractile properties. A potential role for high-protein diet in preventing ectopic lipid deposition needs to be explored in future research. Detrimental effects of high- fat diet on skeletal muscle performance are mitigated by high- protein intake in adult rats but not in old rats.

Pea Proteins Have Anabolic Effects Comparable to Milk Proteins on Whole Body Protein Retention and Muscle Protein Metabolism in Old Rats.

Plant proteins are attracting rising interest due to their pro-health benefits and environmental sustainability. However, little is known about the nutritional value of pea proteins when consumed by older people. Herein, we evaluated the digestibility and nutritional efficiency of pea proteins compared to casein and whey proteins in old rats. Thirty 20-month-old male Wistar rats were assigned to an isoproteic and isocaloric diet containing either casein (CAS), soluble milk protein (WHEY) or Pisane™ pea protein isolate for 16 weeks. The three proteins had a similar effect on nitrogen balance, true digestibility and net protein utilization in old rats, which means that different protein sources did not alter body composition, tissue weight, skeletal muscle protein synthesis or degradation. Muscle mitochondrial activity, inflammation status and insulin resistance were similar between the three groups. In conclusion, old rats used pea protein with the same efficiency as casein or whey proteins, due to its high digestibility and amino acid composition. Using these plant-based proteins could help older people diversify their protein sources and more easily achieve nutritional intake recommendations.