RESUMEN
The high requirement of the gut for threonine has often been ascribed to the synthesis of mucins, secreted threonine-rich glycoproteins protecting the intestinal epithelium from injury. This requirement could be even greater during intestinal inflammation, when mucin synthesis is enhanced. In this study, we used an animal model to investigate the effects of an acute ileitis on threonine splanchnic fluxes. Eight adult multi-catheterized minipigs were fed with an enteral solution. Four of them were subjected to experimental ileitis involving direct administration of trinitrobenzene sulfonic acid (TNBS) into the ileum (TNBS-treated group) and the other 4 were not treated (control group). Threonine fluxes across the portal-drained viscera (PDV) were quantified with the use of simultaneous i.g. L-[(15)N]threonine and i.v. L-[U-(13)C]threonine infusions. Ileal mucosa was sampled for mucin fractional synthesis rate measurement, which was greater in the TNBS-treated group (114 +/- 15%/d) than in the control group (61 +/- 8%/d) (P = 0.021). The first-pass extraction of dietary threonine by the PDV and liver did not differ between groups and accounted for approximately 27 and 10% of the intragastric delivery, respectively. PDV uptake of arterial threonine increased from 25 +/- 14 micromol x kg(-1) x h(-1) in the control group to 171 +/- 35 micromol x kg(-1) x h(-1) in the TNBS-treated group (P < 0.001). In conclusion, ileitis increased intestinal mucin synthesis and PDV utilization of threonine from arterial but not luminal supply. This leads to the mobilization of endogenous proteins to meet the increased threonine demand associated with acute intestinal inflammation.
Asunto(s)
Tracto Gastrointestinal/metabolismo , Ileítis/metabolismo , Mucinas/biosíntesis , Treonina/metabolismo , Alimentación Animal , Animales , Ileítis/tratamiento farmacológico , Inflamación/metabolismo , Porcinos , Porcinos Enanos , Ácido Trinitrobencenosulfónico/uso terapéuticoRESUMEN
The aim of the present study was to determine whether the addition of soluble fibre in the diet affected protein metabolism in the intestinal tissues, some visceral organs and in skeletal muscle. A diet supplemented with pectin (80 g/kg) was fed to young growing rats and the effect on organ mass and protein metabolism in liver, spleen, small and large intestines and gastrocnemius muscle was monitored and compared with the control group. Protein synthesis rates were determined by measuring [13C]valine incorporation in tissue protein. In the pectin-fed rats compared with the controls, DM intake and body weight gain were reduced (9 and 20 %, respectively) as well as gastrocnemius muscle, liver and spleen weights (6, 14 and 11 %, respectively), but the intestinal tissues were increased (64 %). In the intestinal tissues all protein metabolism parameters (protein and RNA content, protein synthesis rate and translational efficiency) were increased in the pectin group. In liver the translational efficiency was also increased, whereas its protein and RNA contents were reduced in the pectin group. In gastrocnemius muscle, protein content, fractional and absolute protein synthesis rates and translational efficiency were lower in the pectin group. The stimulation of protein turnover in intestines and liver by soluble fibre such as pectins could be one of the factors that explain the decrease in muscle turnover and whole-body growth rate.
Asunto(s)
Fibras de la Dieta/farmacología , Sistema Digestivo/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Pectinas/farmacología , Biosíntesis de Proteínas/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Sistema Digestivo/anatomía & histología , Sistema Digestivo/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/anatomía & histología , Intestinos/efectos de los fármacos , Masculino , Músculo Esquelético/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Proteínas/metabolismo , Ratas , Ratas Sprague-Dawley , Bazo/anatomía & histología , Bazo/efectos de los fármacos , Bazo/metabolismoRESUMEN
BACKGROUND: Inflammation is known to affect sulfur amino acid metabolism. Aging is associated with an increased prevalence of inflammatory conditions, but the metabolism of methionine has been poorly explored in the elderly. OBJECTIVES: The aims of this study were to compare methionine kinetics between elderly and young subjects and to explore the effect of aging on the response to a mild inflammatory challenge induced by a vaccination. DESIGN: Seven elderly volunteers aged 66-76 y and 8 young volunteers aged 22-26 y were studied before and 2 d after a vaccination (diphtheria, tetanus, poliomyelitis, and typhoid vaccines). Methionine kinetics were measured by using an infusion of L-[1-13C, methyl-2H3]methionine in the postabsorptive and fed states. RESULTS: Before vaccination, the contribution of homocysteine remethylation to methionine-methyl flux (Qm) and the ratio of remethylation to homocysteine transsulfuration were significantly lower in the elderly subjects than in the young subjects (P < 0.05). In contrast, the contribution of transsulfuration to methionine transmethylation was higher in the elderly (P < 0.05). Vaccination significantly increased the ratio of transsulfuration to transmethylation and decreased the ratio of remethylation to Qm (P < 0.05). CONCLUSIONS: The preferential methionine metabolism toward cysteine synthesis observed after vaccination suggests an increased requirement of sulfur amino acids even in mild inflammatory situations. The main finding of this study is a higher proportion of methionine entering the transsulfuration pathway in elderly subjects before vaccination. This finding suggests an increased cysteine demand during aging.
Asunto(s)
Envejecimiento/metabolismo , Inflamación/metabolismo , Metionina/farmacocinética , Vacunación , Adulto , Anciano , Envejecimiento/fisiología , Isótopos de Carbono , Cisteína/biosíntesis , Cisteína/metabolismo , Deuterio , Femenino , Homocisteína/metabolismo , Humanos , Marcaje Isotópico/métodos , Masculino , Matemática , Metionina/metabolismo , Metilación , Necesidades Nutricionales , Periodo PosprandialRESUMEN
One of the most important effects of aging is sarcopenia, which is associated with impaired locomotion and general weakness. In addition, there is increased susceptibility to illness in aging, which often results in muscle wasting episodes. In such instances, the mobilization of muscle proteins provides free amino acids that are used for energetic purpose, the synthesis of acute phase proteins, and the immune response. However, since muscle protein mass is already depleted, the ability of the aged organism to recover from stress is impaired. Therefore, elucidating the mechanisms that result in sarcopenia is of obvious importance. Age-related changes in protein synthesis and proteolysis are rather small and our current methodology does not enable one to establish unequivocally whether sarcopenia results from depressed protein synthesis, increased proteolysis or both. By contrast, in anabolic and catabolic periods, a number of dysregulations in muscle protein turnover became clearly apparent. The aim of this review is to provide an overview of such altered responses to nutrients and catabolic treatments, which may ultimately contribute to explain sarcopenia. This includes impaired recovery in catabolic states, impaired anabolic effects of nutrients, in particular leucine, and a lack of regulation of the ubiquitin-proteasome proteolytic system. These alterations are discussed with respect to modifications in the insulin/IGF-1 axis and glucocorticoid related effects.
Asunto(s)
Envejecimiento/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Aminoácidos/metabolismo , Aminoácidos/farmacología , Glucocorticoides/farmacología , Glucocorticoides/uso terapéutico , Humanos , Insulina/metabolismo , Insulina/farmacología , Factor I del Crecimiento Similar a la Insulina/metabolismo , InaniciónRESUMEN
To further explore whether immune function and acute phase response are altered during ageing, the response to a mild inflammatory stress (DT-Polio-Typhim vaccination) was studied in elderly and young subjects. Cytokine production (IFN-gamma, TNF-alpha, IL-6, IL-10) by whole blood cultures, circulating cytokines and acute phase proteins were analysed before and 2 days after vaccination. Prior to vaccination, only IFN-gamma production was lower in the elderly than in the young subjects due to a lower mononuclear cell number. In the same time, although in the normal range, several acute phase proteins were greater in elderly than in young subjects, suggesting a low-grade inflammatory state in the elderly. After vaccination, IFN-gamma production remained lower in the elderly than in the young, supporting an altered cell-mediated immunity with advancing age. TNF-alpha production was unaffected by either ageing or vaccination. IL-6 production was stimulated by vaccination in young subjects but not significantly in the elderly. IL-10 production was inhibited by vaccination in the elderly but not in the young. Acute phase proteins were less increased in elderly than in young subjects. Taken together, these results support a general lack of inflammatory response in the elderly exposed to an immune challenge and suggest that immune deficiency may concern both Th1 and Th2 responses. However, the interpretation must respect the limitation of small subjects number.
Asunto(s)
Envejecimiento , Proteínas de Fase Aguda/metabolismo , Adulto , Factores de Edad , Anciano , Citocinas/biosíntesis , Vacuna contra Difteria, Tétanos y Tos Ferina , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunidad Celular , Inflamación , Interferón gamma/metabolismo , Interleucina-10/biosíntesis , Interleucina-6/biosíntesis , Leucocitos Mononucleares/citología , Masculino , Células TH1/metabolismo , Células Th2/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis , Vacunas Tifoides-Paratifoides , VacunaciónRESUMEN
The free radical theory of aging proposes that oxidative stress plays a key role in the aging process. By altering muscle protein degradation rates, it could accelerate the age-related loss of muscle proteins. Glutathione (GSH), one of the main body antioxidants, could prevent this phenomenon, but its concentration decreases during aging. Our aims were to have a better understanding of the mechanisms of the age-related decrease in glutathione availability and of the links with sarcopenia. Male Wistar rats aged 6, 9, 12, 15, 19, 22, 25 and 28 months (n = 6 per age) were used to measure plasma and skeletal muscle protein carbonyl content, plasma total and free cyst(e)ine content, liver and muscle glutathione content as well as liver GSSG reductase, GSH peroxidase, GSH transferase and gamma glutamyl cysteine synthetase (GCS) activities. Although tissue glutathione content decreased with age, the other markers of oxidative stress were little changed during aging. In particular, muscle protein carbonyl content was unchanged. Variations in glutathione availability were not explained by cyst(e)ine availability but depended on gamma GCS activity. The stability of skeletal muscle carbonyl content during aging suggests a very efficient degradation of oxidized proteins in muscle.
Asunto(s)
Envejecimiento/metabolismo , Glutatión/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Envejecimiento/fisiología , Animales , Peso Corporal/fisiología , Cisteína/sangre , Hígado/anatomía & histología , Hígado/metabolismo , Masculino , Músculo Esquelético/anatomía & histología , Tamaño de los Órganos/fisiología , Estrés Oxidativo/fisiología , Ratas , Ratas WistarRESUMEN
The aim of this work was to test the hypothesis that the trophic effect of lentil feeding on large intestine results from a stimulation of protein synthesis and to determine whether it interferes with protein metabolism in other splanchnic or peripheral organs. Two groups of growing Sprague Dawley male rats were pair-fed iso-caloric iso-nitrogenous balanced diets containing either cooked lentils (Lens esculenta puyensis) or casein as unique protein source. Protein synthesis rates were measured in vivo, in large intestine, liver and gastrocnemius at the postprandial state. In large intestine, protein and ribonucleic acid contents were higher in the lentil-fed group than in the control group, and the amount of proteins synthesized was also higher (+57%). By contrast, liver protein and ribonucleic acid contents as well as protein synthesis rates were significantly lower in the lentil-fed group than in the control group. In the gastrocnemius muscle protein and ribonucleic acid contents were significantly lower and the amount of protein synthesized was also lower (-18%) in the lentil fed group than in the control group. This study suggests that stimulation of protein synthesis in the large intestine is compensated for by a decrease in liver and muscle.
Asunto(s)
Alimentación Animal , Proteínas en la Dieta , Intestino Grueso/metabolismo , Lens (Planta) , Hígado/metabolismo , Músculo Esquelético/metabolismo , Biosíntesis de Proteínas , Animales , Peso Corporal , Dieta , Ingestión de Energía , Masculino , ARN/metabolismo , Ratas , Ratas Sprague-Dawley , Ribosomas/metabolismoRESUMEN
Glutamine is the major fuel for enterocytes and promotes the growth of intestinal mucosa. Although oral glutamine exerts a positive effect on intestinal villus height in very old rats, how glutamine is used by enterocytes is unclear. Adult (8 months) and very old (27 months) female rats were exposed to intermittent glutamine supplementation for 50% of their age lifetime. Treated rats received glutamine added to their drinking water, and control rats received water alone. Jejunal epithelial cells (~300×10(6) cells) were incubated in oxygenated Krebs-Henseleit buffer for 30 min containing [1-(13)C] glutamine (~17 M) for analysis of glutamine metabolites by (13)C nuclear magnetic resonance ((13)C NMR). An aliquot fraction was incubated in the presence of [U-(14)C] glutamine to measure produced CO2. Glutamine pretreatment increased glutamate production and decreased CO2 production in very old rats. The ratio CO2/glutamate, which was very high in control very old rats, was similar at both ages after glutamine pretreatment, as if enterocytes from very old rats recovered the metabolic abilities of enterocytes from adult rats. Our results suggest that long-term treatment with glutamine started before advanced age (a) prevented the loss of rat body weight without limiting sarcopenia and (b) had a beneficial effect on enterocytes from very old rats probably by favoring the role of glutamate as a precursor for glutathione, arginine and proline biosynthesis, which was not detected in (13)C NMR spectra in our experimental conditions.
Asunto(s)
Envejecimiento/metabolismo , Dióxido de Carbono/metabolismo , Enterocitos/metabolismo , Ácido Glutámico/biosíntesis , Glutamina/metabolismo , Animales , Ratas , Ratas WistarRESUMEN
The protein content in foodstuffs is estimated by multiplying the determined nitrogen content by a nitrogen-to-protein conversion factor. Jones' factors for a series of foodstuffs, including 6.25 as the standard, default conversion factor, have now been used for 75 years. This review provides a brief history of these factors and their underlying paradigm, with an insight into what is meant by "protein." We also review other compelling data on specific conversion factors which may have been overlooked. On the one hand, when 6.25 is used irrespective of the foodstuff, "protein" is simply nitrogen expressed using a different unit and says little about protein (s.s.). On the other hand, conversion factors specific to foodstuffs, such as those provided by Jones, are scientifically flawed. However, the nitrogen:protein ratio does vary according to the foodstuff considered. Therefore, from a scientific point of view, it would be reasonable not to apply current specific factors any longer, but they have continued to be used because scientists fear opening the Pandora's box. But because conversion factors are critical to enabling the simple conversion of determined nitrogen values into protein values and thus accurately evaluating the quantity and the quality of protein in foodstuffs, we propose a set of specific conversion factors for different foodstuffs, together with a default conversion factor (5.6). This would be far more accurate and scientifically sound, and preferable when specifically expressing nitrogen as protein. These factors are of particular importance when "protein" basically means "amino acids," this being the principal nutritional viewpoint.
Asunto(s)
Aminoácidos/análisis , Nitrógeno/análisis , Proteínas/análisis , Proteínas/normas , Análisis de los Alimentos , Humanos , Valor NutritivoRESUMEN
Characterisation and identification of peptides (800 to 5000 Da) generated by intestinal digestion of fish or meat were performed using MS analyses (matrix-assisted laser desorption ionisation time of flight and nano-liquid chromatography electrospray-ionisation ion trap MS/MS). Four pigs fitted with cannulas at the duodenum and jejunum received a meal exclusively made of cooked Pectoralis profundus beef meat or cooked trout fillets. A protein-free meal, made of free amino acids, starch and fat, was used to identify peptides of endogenous origin. Peptides reproducibly detected in digesta (i.e. from at least three pigs) were evidenced predominantly in the first 3 h after the meal. In the duodenum, most of the fish- and meat-derived peptides were characteristic of a peptic digestion. In the jejunum, the majority of peptides appeared to result from digestion by chymotrypsin and trypsin. Despite slight differences in gastric emptying kinetics and overall peptide production, possibly in relation to food structure and texture, six and four similar peptides were released after ingestion of fish or meat in the duodenum and jejunum. A total of twenty-six different peptides were identified in digesta. All were fragments of major structural (actin, myosin) or sarcoplasmic (creatine kinase, glyceraldehyde-3-phosphate dehydrogenase and myoglobin) muscle proteins. Peptides were short ( < 2000 Da) and particularly rich in proline residues. Nineteen of them contained bioactive sequences corresponding mainly to an antihypertensive activity. The present work showed that after fish or meat ingestion, among the wide variety of peptides produced by enzymic digestion, some of them can be reproducibly observed in intestinal digesta.
Asunto(s)
Bovinos , Digestión , Carne , Fragmentos de Péptidos/metabolismo , Porcinos/metabolismo , Trucha , Animales , Antihipertensivos/metabolismo , Duodeno/metabolismo , Alimentos , Contenido Digestivo/química , Yeyuno/metabolismo , Modelos Animales , Proteínas Musculares/metabolismo , Fragmentos de Péptidos/análisis , Distribución Aleatoria , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
PURPOSE OF REVIEW: The delivery rate of amino acids to an organism significantly affects protein anabolism. The rate can be controlled by the type and the timing of feeding. Our aim was to bring new insights to the way they may act. RECENT FINDINGS: During young and adult ages, when food supply is liberal, subjects can adapt to various modes of protein feeding. However, during food restriction, protein anabolism is favored when the delivery of amino acids is evenly distributed over the day, either with frequent meals, or through the use of slowly absorbed proteins like casein. In contrast, during aging, quickly absorbed protein sources become more efficient. During recovery after exercise, the timing of protein feeding after the end of exercise may or may not influence its anabolic effect, depending on the subject's age and the type of exercise. SUMMARY: The synchronization of variations in anabolic capability with amino acid supply partly explains the effects of the type and timing of protein feeding. This effect is modulated by the amount of amino acids required to increase whole-body proteins and by the signaling properties of some amino acids to stimulate protein synthesis. Indeed, the anabolic effect of amino acids is determined by their interaction with other anabolic factors (other nutrients or physiological factors, whose efficiency is mainly related to their effect on protein degradation). It is clear that benefits can be obtained from adapted protein feeding patterns.
Asunto(s)
Proteínas en la Dieta/administración & dosificación , Biosíntesis de Proteínas , Absorción , Envejecimiento , Aminoácidos/administración & dosificación , Aminoácidos/sangre , Aminoácidos/metabolismo , Dieta , Ingestión de Energía , Ejercicio Físico , Femenino , Humanos , Masculino , Proteínas Musculares/biosíntesis , Factores de TiempoRESUMEN
Dietary CLA isomers were shown to reduce adipose tissues in growing animals, mainly in mice, but their effects in adult animals remain unclear. This study was conducted to determine whether these effects depend on the isomer fed, on physical activity, or on the initial level of body fat. Male Wistar rats (4 mo old) were fed for 6 wk diets containing either no CLA, the cis-9, trans-11 CLA isomer (10 g/kg), the trans-10, cis-12 CLA isomer (10 g/kg), or both isomers (10 g/kg each). Half of the rats were assigned to exercise by treadmill running (1 h/d, 22 m/min). The initial body fat level was normal (12.7%) in a first trial, and high (18.9%) in a second trial. Chemical and anatomical body compositions were determined by chemical analysis and organ dissection. In both trials, the CLA diets, whatever the isomer, had no effect on food intake and body weight changes, on body chemical composition (fat, protein and water contents or gains), or on the body anatomical composition (weights or gains in epididymal and perirenal adipose tissues, in liver and in 4 muscles). There was no interaction between CLA treatment and physical activity. In conclusion, adult male rats do not appear to be responsive to the fat-to-lean partitioning effect of CLA described in growing rats. This was not affected by exercise or initial body fat level.