Plant Protein Can Be as Efficient as Milk Protein to Maintain Fat Free Mass in Old Rats, Even When Fat and Sugar Intakes Are High.

BACKGROUND: Alternative, sustainable, and adequate sources of protein must be found to meet global demand. OBJECTIVES: Our aim was to assess the effect of a plant protein blend with a good balance of indispensable amino acids and high contents of leucine, arginine, and cysteine on the maintenance of muscle protein mass and function during aging in comparison to milk proteins and to determine if this effect varied according to the quality of the background diet. METHODS: Old male Wistar rats (n = 96, 18 mo old) were randomly allocated for 4 mo to 1 of 4 diets, differing according to protein source (milk or plant protein blend) and energy content (standard, 3.6 kcal/g, with starch, or high, 4.9 kcal/g, with saturated fat and sucrose). We measured: every 2 mo, body composition and plasma biochemistry; before and after 4 mo, muscle functionality; after 4 mo, in vivo muscle protein synthesis (flooding dose of L-[1-13C]-valine) and muscle, liver, and heart weights. Two-factor ANOVA and repeated measures 2-factor ANOVA were conducted. RESULTS: There was no difference between protein type on the maintenance during aging of lean body mass, muscle mass, and muscle functionality. The high-energy diet significantly increased body fat (+47%) and heart weight (+8%) compared to the standard energy diet but had no effect on fasting plasma glucose and insulin. Muscle protein synthesis was significantly stimulated by feeding to the same extent in all groups (+13%). CONCLUSIONS: Since high-energy diets had little impact on insulin sensitivity and related metabolism, we could not test the hypothesis that in situations of higher insulin resistance, our plant protein blend may be better than milk protein. However, this rat study offers significant proof of concept from the nutritional standpoint that appropriately blended plant proteins can have high nutritional value even in demanding situations such as aging protein metabolism.

Lysine and homoarginine are closely interrelated metabolites in the rat.

L-Lysine (Lys) and L-arginine (Arg), but not L-homoarginine (hArg), are proteinogenic amino acids. In healthy humans, oral administration of hArg increased the plasma concentration of Lys, suggesting Lys as a metabolite of hArg. In humans and animals, hArg is biosynthesized from Arg and Lys by arginine:glycine amidinotransferase (AGAT). In vitro, recombinant human arginase and bovine liver arginase I hydrolyzed hArg to Lys, suggesting Lys as a metabolite of hArg. The aim of the present study was to investigate whether changes in blood concentrations of hArg and Lys in old rats fed for 4 months with varied controlled experimental diets could suggest interconversion of these amino acids. Blood samples (n = 253) were taken before (T0) and after 2 months (T2) and 4 months (T4) of the experiment. Plasma concentrations of Lys and hArg were determined by gas chromatography-mass spectrometry. The plasma hArg concentration markedly correlated with the plasma Lys concentration at all timepoints (r ≥ 0.7, P < 0.0001). Further analysis demonstrated that hArg and Lys are closely and specifically associated independently of experimental time/rat age and diet, suggesting that hArg and Lys are mutual metabolites in old rats. Based on the plasma concentration changes, the median yield of hArg from Lys was determined to be 0.17% at T0 and each 0.27% at T2 and T4. With a circulating concentration of about 3 µM, hArg a major metabolite of Lys in healthy humans. hArg supplementation is currently investigated as a cardioprotective means to improve impaired hArg synthesis. Present knowledge suggests that Lys rather than hArg supplementation may be even more favorable.

Important determinants to take into account to optimize protein nutrition in the elderly: solutions to a complex equation.

During ageing, skeletal muscle develops anabolic resistance towards the stimulation of protein synthesis induced by dietary amino acids. The stimulation of muscle protein synthesis after food intake remains insufficient, even with a protein intake recommended for healthy adults. This alteration is one of the mechanisms known to be responsible for the decrease of muscle mass and function during ageing, namely sarcopenia. Increasing dietary protein intake above the current RDA(0⋅83 g/kg/d) has been strongly suggested to overcome the anabolic resistance observed. It is also specified that the dietary protein ingested should be of good quality. A protein of good quality is a protein whose amino acid (AA) composition covers the requirement of each AA when ingested at the RDA. However, the biological value of proteins may vary among dietary sources in which AA composition could be unbalanced. In the present review, we suggest that the quality of a dietary protein is also related to several other determinants. These determinants include the speed of digestion of dietary proteins, the presence of specific AA, the food matrix in which the dietary proteins are included, the processes involved in the production of food products (milk gelation and cooking temperature), the energy supply and its nature, and the interaction between nutrients before ingestion. Particular attention is given to plant proteins for nutrition of the elderly. Finally, the timing of protein intake and its association with the desynchronized intake of energetic nutrients are discussed.

Post Meal Energy Boluses Do Not Increase the Duration of Muscle Protein Synthesis Stimulation in Two Anabolic Resistant Situations.

BACKGROUND: When given in the long term, whey proteins alone do not appear to be an optimal nutritional strategy to prevent or slow down muscle wasting during aging or catabolic states. It has been hypothesized that the digestion of whey may be too rapid during a catabolic situation to sustain the anabolic postprandial amino acid requirement necessary to elicit an optimal anabolic response. Interestingly, it has been shown recently that the duration of the postprandial stimulation of muscle protein synthesis in healthy conditions can be prolonged by the supplementary ingestion of a desynchronized carbohydrate load after food intake. We verified this hypothesis in the present study in two different cases of muscle wasting associated with anabolic resistance, i.e., glucocorticoid treatment and aging. METHODS: Multi-catheterized minipigs were treated or not with glucocorticoids for 8 days. Muscle protein synthesis was measured sequentially over time after the infusion of a 13C phenylalanine tracer using the arterio-venous method before and after whey protein meal ingestion. The energy bolus was given 150 min after the meal. For the aging study, aged rats were fed the whey meal and muscle protein synthesis was measured sequentially over time with the flooding dose method using 13C Valine. The energy bolus was given 210 min after the meal. RESULTS: Glucocorticoid treatment resulted in a decrease in the duration of the stimulation of muscle protein synthesis. The energy bolus given after food intake was unable to prolong this stimulation despite a simultaneous increase of insulin and glucose following its absorption. In old rats, a similar observation was made with no effect of the energy bolus on the duration of the muscle anabolic response following whey protein meal intake. CONCLUSIONS: Despite very promising observations in healthy situations, the strategy aimed at increasing muscle protein synthesis stimulation by giving an energy bolus during the postprandial period remained inefficient in our two anabolic resistance models.

Impaired Skeletal Muscle Branched-Chain Amino Acids Catabolism Contributes to Their Increased Circulating Levels in a Non-Obese Insulin-Resistant Fructose-Fed Rat Model.

Elevated plasma branched-chain amino acids (BCAA) levels are often observed in obese insulin-resistant (IR) subjects and laboratory animals. A reduced capacity of the adipose tissues (AT) to catabolize BCAA has been proposed as an explanation, but it seems restricted to obesity models of genetically modified or high fat⁻fed rodents. We aimed to determine if plasma BCAA levels were increased in a model of IR without obesity and to explore the underlying mechanisms. Rats were fed with a standard diet, containing either starch or fructose. BCAA levels, body weight and composition were recorded before and after 5, 12, 30, or 45 days of feeding. Elevated blood BCAA levels were observed in our IR model with unaltered body weight and composition. No changes were observed in the liver or the AT, but instead an impaired capacity of the skeletal muscle to catabolize BCAA was observed, including reduced capacity for transamination and oxidative deamination. Although the elevated blood BCAA levels in the fructose-fed rat seem to be a common feature of the IR phenotype observed in obese subjects and high fat⁻fed animals, the mechanisms involved in such a metabolic phenomenon are different, likely involving the skeletal muscle BCAA metabolism.

A meal with mixed soy/whey proteins is as efficient as a whey meal in counteracting the age-related muscle anabolic resistance only if the protein content and leucine levels are increased.

With aging, skeletal muscle becomes resistant to the anabolic effect of dietary proteins and sarcopenia develops. Animal proteins, which are rich in leucine, are recommended for the elderly, but it is not known whether their replacement by plant proteins would maintain the health and physical independence of this population. Aged rats were fed with animal proteins (casein and whey proteins) with different leucine contents and compared to rats fed with diets in which whey was substituted with soy proteins and by increasing the total protein content or not. Our results clearly showed that the meal with mixed soy/whey proteins allowed the anabolic response of skeletal muscle during aging only if the protein content was increased by 25%. Indeed, if the protein content of the soy/whey diet was decreased to a similar protein content such as a whey diet, i.e. 13%, the anabolic effect decreased. The same observation was recorded if the whey proteins were totally substituted with soy proteins.

Effect of high chronic intake of sucrose on liver metabolism in aging rats. Modulation by rutin and micronutrients

High-sugar intake and senescence share common deleterious effects, in particular in liver, but combination of these two factors was little studied. Our aims were to examine the effect of a high-sucrose diet in liver of old rats and also the potential benefices of a polyphenol/micronutrient supplementation. Four groups of 22-month-old male rats fed during 5 months with a diet containing either 13 or 62% sucrose, supplemented or not with rutin, vitamin E, A, D, selenium, and zinc were compared. We measured liver macronutrient composition, glycation/oxidative stress, enzyme activities (lipogenesis, Beta-oxidation, fructokinase), gene expression (enzymes and transcription factors), in vivo protein synthesis rates and plasma parameters. Sucrose induced an increase in plasma and liver lipid content, and a stimulation of liver protein synthesis rates. Gene expression was little changed by sucrose, with lower levels for LXR-alfa and LXR-Beta. Polyphenol/micronutrient supplementation tended to limit liver triglyceride infiltration through variations in fatty acid synthase, acyl coA oxidase, and possibly ATP-citrate lyase activities. In conclusion, despite differences in enzymatic regulations, and blunted responses of gene expression, high-sucrose diet was still able to induce a marked increase in liver lipid content in old animals. However, it probably attenuated the positive impact of polyphenol/micronutrients

No disponible

Effects of nutritional state, aging and high chronic intake of sucrose on brain protein synthesis in rats: modulation of it by rutin and other micronutrients.

Little is still known about brain protein synthesis. In order to increase our knowledge of it, we aimed to modulate brain protein synthesis rates through aging, variations in nutritional state (fed state vs. fasted state), high sucrose diet and micronutrient supplementation. Four groups of 16 month-old male rats were fed for five months with a diet containing either 13% or 62% sucrose (wheat starch was replaced with sucrose), supplemented or not with rutin (5 g kg-1 diet), vitamin E (4×), A (2×), D (5×), selenium (10×) and zinc (+44%) and compared with an adult control group. We measured cerebellum protein synthesis and hippocampus gene expression of antioxidant enzymes, inflammatory cytokines and transcription factors. We showed that cerebellum protein synthesis was unchanged by the nutritional state, decreased during aging (-8%), and restored to the adult level by micronutrient supplementation. Sucrose diet did not change protein synthesis but reduced the protein content. Micronutrient supplementation had no effect in sucrose fed rats. Hippocampus gene expressions were affected by age (an increase of TNF-α), sucrose treatment (an increase of IL-1ß and IL-6), and micronutrient supplementation (a decrease of heme oxygenase, catalase, glutathione peroxidase, TNF-α, and Nrf2). We noted that cerebellum protein synthesis and hippocampus TNF-α gene expression were modulated by the same factors: they were affected by aging and micronutrient supplementation and unchanged by feeding and by high sucrose diet.

Effect of high chronic intake of sucrose on liver metabolism in aging rats. Modulation by rutin and micronutrients.

High-sugar intake and senescence share common deleterious effects, in particular in liver, but combination of these two factors was little studied. Our aims were to examine the effect of a high-sucrose diet in liver of old rats and also the potential benefices of a polyphenol/micronutrient supplementation. Four groups of 22-month-old male rats fed during 5 months with a diet containing either 13 or 62% sucrose, supplemented or not with rutin, vitamin E, A, D, selenium, and zinc were compared. We measured liver macronutrient composition, glycation/oxidative stress, enzyme activities (lipogenesis, ß-oxidation, fructokinase), gene expression (enzymes and transcription factors), in vivo protein synthesis rates and plasma parameters. Sucrose induced an increase in plasma and liver lipid content, and a stimulation of liver protein synthesis rates. Gene expression was little changed by sucrose, with lower levels for LXR-α and LXR-ß. Polyphenol/micronutrient supplementation tended to limit liver triglyceride infiltration through variations in fatty acid synthase, acyl coA oxidase, and possibly ATP-citrate lyase activities. In conclusion, despite differences in enzymatic regulations, and blunted responses of gene expression, high-sucrose diet was still able to induce a marked increase in liver lipid content in old animals. However, it probably attenuated the positive impact of polyphenol/micronutrients.

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.

At same leucine intake, a whey/plant protein blend is not as effective as whey to initiate a transient post prandial muscle anabolic response during a catabolic state in mini pigs.

BACKGROUND: Muscle atrophy has been explained by an anabolic resistance following food intake and an increase of dietary protein intake is recommended. To be optimal, a dietary protein has to be effective not only to initiate but also to prolong a muscle anabolic response in a catabolic state. To our knowledge, whether or not a dairy or a dairy/plant protein blend fulfills these criterions is unknown in a muscle wasting situation. OBJECTIVE: Our aim was, in a control and a catabolic state, to measure continuously muscle anabolism in term of intensity and duration in response to a meal containing casein (CAS), whey (WHEY) or a whey/ plant protein blend (BLEND) and to evaluate the best protein source to elicit the best post prandial anabolism according to the physio-pathological state. METHODS: Adult male Yucatan mini pigs were infused with U-13C-Phenylalanine and fed either CAS, WHEY or BLEND. A catabolic state was induced by a glucocorticoid treatment for 8 days (DEX). Muscle protein synthesis, proteolysis and balance were measured with the hind limb arterio-venous differences technique. Repeated time variance analysis were used to assess significant differences. RESULTS: In a catabolic situation, whey proteins were able to initiate muscle anabolism which remained transient in contrast to the stimulated muscle protein accretion with WHEY, CAS or BLEND in healthy conditions. Despite the same leucine intake compared to WHEY, BLEND did not restore a positive protein balance in DEX animals. CONCLUSIONS: Even with WHEY, the duration of the anabolic response was not optimal and has to be improved in a catabolic state. The use of BLEND remained of lower efficiency even at same leucine intake than whey.

In the elderly, meat protein assimilation from rare meat is lower than that from meat that is well done.

Background: Meat cooking conditions in in vitro and in vivo models have been shown to influence the rate of protein digestion, which is known to affect postprandial protein metabolism in the elderly.Objective: The present study was conducted to demonstrate the effect of cooking conditions on meat protein assimilation in the elderly. We used a single-meal protocol to assess the meat protein absorption rate and estimate postprandial meat protein utilization in elderly subjects.Design: The study recruited 10 elderly volunteers aged 70-82 y. Each received, on 2 separate occasions, a test meal exclusively composed of intrinsically 15N-labeled bovine meat (30 g protein), cooked at 55°C for 5 min [rare meat (RM)] or at 90°C for 30 min [fully cooked meat (FCM)], and minced. Whole-body fluxes of leucine, before and after the meal, were determined with the use of a [1-13C]leucine intravenous infusion. Meat protein absorption was recorded with the use of 15N enrichment of amino acids.Results: Postprandial time course observations showed a lower concentration in the plasma of indispensable amino acids (P < 0.01), a lower entry rate of meat leucine in the plasma (P < 0.01), and a lower contribution of meat nitrogen to plasma amino acid nitrogen (P < 0.001), evidencing lower peripheral bioavailability of meat amino acids with RM than with FCM. This was associated with decreased postprandial whole-body protein synthesis with RM than with FCM (40% compared with 56% of leucine intake, respectively; P < 0.01).Conclusions: Whereas meat cooking conditions have little effect on postprandial protein utilization in young adults, the present work showed that the bioavailability and assimilation of meat amino acids in the elderly is lower when meat is poorly cooked. In view to preventing sarcopenia, elderly subjects should be advised to favor the consumption of well-cooked meat. This trial was registered at clinicaltrials.gov as NCT02157805.

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.

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.

Assessment of protein modifications in liver of rats under chronic treatment with paracetamol (acetaminophen) using two complementary mass spectrometry-based metabolomic approaches.

Liver protein can be altered under paracetamol (APAP) treatment. APAP-protein adducts and other protein modifications (oxidation/nitration, expression) play a role in hepatotoxicity induced by acute overdoses, but it is unknown whether liver protein modifications occur during long-term treatment with non-toxic doses of APAP. We quantified APAP-protein adducts and assessed other protein modifications in the liver from rats under chronic (17 days) treatment with two APAP doses (0.5% or 1% of APAP in the diet w/w). A targeted metabolomic method was validated and used to quantify APAP-protein adducts as APAP-cysteine adducts following proteolytic hydrolysis. The limit of detection was found to be 7ng APAP-cysteine/mL hydrolysate i.e. an APAP-Cys to tyrosine ratio of 0.016‰. Other protein modifications were assessed on the same protein hydrolysate by untargeted metabolomics including a new strategy to process the data and identify discriminant molecules. These two complementary mass spectrometry (MS)-based metabolic approaches enabled the assessment of a wide range of protein modifications induced by chronic treatment with APAP. BIOLOGICAL SIGNIFICANCE: APAP-protein adducts were detected even in the absence of glutathione depletion and hepatotoxicity, i.e. in the 0.5% APAP group, and increased by 218% in the 1% APAP group compared to the 0.5% APAP group. At the same time, the untargeted metabolomic method revealed a decrease in the binding of cysteine, cysteinyl-glycine and GSH to thiol groups of protein cysteine residues, an increase in the oxidation of tryptophan and proline residues and a modification in protein expression. This wide range of modifications in liver proteins occurred in rats under chronic treatment with APAP that did not induce hepatotoxicity.

High whey protein intake delayed the loss of lean body mass in healthy old rats, whereas protein type and polyphenol/antioxidant supplementation had no effects.

Our aim was to compare and combine 3 nutritional strategies to slow down the age-related loss of muscle mass in healthy old rats: 1) increase protein intake, which is likely to stimulate muscle protein anabolism; 2) use leucine rich, rapidly digested whey proteins as protein source (whey proteins are recognized as the most effective proteins to stimulate muscle protein anabolism). 3) Supplement animals with a mixture of chamomile extract, vitamin E, vitamin D (reducing inflammation and oxidative stress is also effective to improve muscle anabolism). Such comparisons and combinations were never tested before. Nutritional groups were: casein 12% protein, whey 12% protein, whey 18% protein and each of these groups were supplemented or not with polyphenols/antioxidants. During 6 months, we followed changes of weight, food intake, inflammation (plasma fibrinogen and alpha-2-macroglobulin) and body composition (DXA). After 6 months, we measured muscle mass, in vivo and ex-vivo fed and post-absorptive muscle protein synthesis, ex-vivo muscle proteolysis, and oxidative stress parameters (liver and muscle glutathione, SOD and total antioxidant activities, muscle carbonyls and TBARS). We showed that although micronutrient supplementation reduced inflammation and oxidative stress, the only factor that significantly reduced the loss of lean body mass was the increase in whey protein intake, with no detectable effect on muscle protein synthesis, and a tendency to reduce muscle proteolysis. We conclude that in healthy rats, increasing protein intake is an effective way to delay sarcopenia.

Hibernoma: a clinical model for exploring the role of brown adipose tissue in the regulation of body weight?

CONTEXT: Hibernoma is a rare benign tumor histologically similar to brown adipose tissue. Some studies reported weight loss in patients with this tumor; however, the mechanisms have never been investigated. OBJECTIVE: The purpose of this study is to explore the impact of hibernoma resection on the whole-body metabolism. PATIENT AND METHODS: A 68-year-old woman was examined after a weight loss of 10 kg in 6 months. Body composition, food intake, physical activity, blood levels of thyroid hormones, and lipid profile were assessed before surgery and during 1 year after surgery. The patient's resting energy expenditure (REE) over time was compared to a control group of 18 matched healthy volunteers. RESULTS: Within 1 year after hibernoma resection, the patient gained 15 kg of body weight. This was associated with fat mass gain (+41%), mainly in the abdominal region (+48%). The patient also developed hepatic nonalcoholic steatosis, mild hypertriglyceridemia, and reduced levels of high-density lipoproteins. REE increased during the dynamic phase of weight gain, compared to the presurgery measurement, and returned to baseline after 1 year. Food intake was increased by 37.5% 6 weeks after resection of the hibernoma and returned to baseline values within 6 months. CONCLUSIONS: In our study conditions, hibernoma did not alter REE, but weight gain did. Specific physical activities and dietetic follow-ups are suggested for those patients to prevent excess fat mass gain and metabolic disorders after hibernoma resection. More studies should focus on hibernoma mechanisms inducing weight loss.

Protein feeding pattern, casein feeding, or milk-soluble protein feeding did not change the evolution of body composition during a short-term weight loss program.

Studies have shown that timing of protein intake, leucine content, and speed of digestion significantly affect postprandial protein utilization. Our aim was to determine if one can spare lean body mass during energy restriction by varying the quality and the timing of protein intake. Obese volunteers followed a 6-wk restricted energy diet. Four groups were compared: casein pulse, casein spread, milk-soluble protein (MSP, = whey) pulse, and MSP spread (n = 10-11 per group). In casein groups, caseins were the only protein source; it was MSP in MSP groups. Proteins were distributed in four meals per day in the proportion 8:80:4:8% in the pulse groups; it was 25:25:25:25% in the spread groups. We measured weight, body composition, nitrogen balance, 3-methylhistidine excretion, perception of hunger, plasma parameters, adipose tissue metabolism, and whole body protein metabolism. Volunteers lost 7.5 ± 0.4 kg of weight, 5.1 ± 0.2 kg of fat, and 2.2 ± 0.2 kg of lean mass, with no difference between groups. In adipose tissue, cell size and mRNA expression of various genes were reduced with no difference between groups. Hunger perception was also never different between groups. In the last week, due to a higher inhibition of protein degradation and despite a lower stimulation of protein synthesis, postprandial balance between whole body protein synthesis and degradation was better with caseins than with MSP. It seems likely that the positive effect of caseins on protein balance occurred only at the end of the experiment.