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Inflammatory bowel diseases are chronic inflammation of the intestinal mucosa characterized by relapsing–remitting cycle periods of variable duration. Infliximab (IFX) was the first monoclonal antibody used for the treatment of Crohn’s disease and ulcerative colitis (UC). High variability between treated patients and loss of IFX efficiency over time support the further development of drug therapy. An innovative approach has been suggested based on the presence of orexin receptor (OX1R) in the inflamed human epithelium of UC patients. In that context, the aim of this study was to compare, in a mouse model of chemically induced colitis, the efficacy of IFX compared to the hypothalamic peptide orexin-A (OxA). C57BL/6 mice received 3.5% dextran sodium sulfate (DSS) in drinking water for 5 days. Since the inflammatory flare was maximal at day 7, IFX or OxA was administered based on a curative perspective at that time for 4 days using intraperitoneal injection. Treatment with OxA promoted mucosal healing and decreased colonic myeloperoxidase activity, circulating concentrations of lipopolysaccharide-binding protein, IL-6 and tumor necrosis factor alpha (TNFα) and decreased expression of genes encoding cytokines in colonic tissues with better efficacy than IFX allowing for more rapid re-epithelization. This study demonstrates the comparable anti-inflammatory properties of OxA and IFX and shows that OxA is efficient in promoting mucosal healing, suggesting that OxA treatment is a promising new biotherapy.

Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system. These past 20 years had revealed that orexins/receptors system was also present in the peripheral nervous system where they participated to the regulation of multiple functions including blood pressure regulation, intestinal motility, hormone secretion, lipolyze and reproduction functions. Associated to these peripheral functions, it was found that orexins and their receptors were involved in various diseases such as acute/chronic inflammation, metabolic syndrome and cancers. The present review suggests that orexins or the orexin neural circuitry represent potential therapeutic targets for the treatment of multiple pathologies related to inflammation including intestinal bowel disease, multiple sclerosis and septic shock, obesity and digestive cancers.

Amino acid supplementation may be indicated to correct for insufficient amino acid intake in healthy individuals, and in specific physiological or pathophysiological situations. However, there is a concern to not supplement beyond the tolerable upper intake level (UL) by determining parameters of no-observed-adverse-effect level (NOAEL) or lowest-observed-adverse-effect level (LOAEL) for each amino acid. Since the NOAEL and LOAEL values are at least one order of magnitude different when comparing the values obtained in rats and humans, the aim of this review is to evaluate to what extent the amino acid UL measured in the rat model, when referenced to the dietary usual consumption (UC) and dietary requirement (RQ) for indispensable amino acids, may be used as an approximation of the UL in humans. This review then compares the ratios of the NOAEL or LOAEL over UC and RQ in the rat model with the same ratios calculated in humans for the nine amino acids (arginine, serine, glycine, histidine, leucine, lysine, methionine, phenylalanine, and tryptophan) for which this comparison can be done. From the calculations made, it appears that for these 9 amino acids, the calculated ratios for rats and humans, although rather different for several amino acids, remains for all of them in the same order of magnitude. For tryptophan, tyrosine, and valine, the ratios calculated in rats are markedly different according to the sex of animals, raising the view that it may be also the case in humans.

The metabolism of methionine and cysteine in the body tissues determines the concentrations of several metabolites with various biologic activities, including homocysteine, hydrogen sulfide (H2S), taurine, and glutathione. Hyperhomocysteinemia, which is correlated with lower HDL cholesterol in blood in volunteers and animal models, has been associated with an increased risk for cardiovascular diseases. In humans, the relation between methionine intake and hyperhomocysteinemia is dependent on vitamin status (vitamins B-6 and B-12 and folic acid) and on the supply of other amino acids. However, lowering homocysteinemia by itself is not sufficient for decreasing the risk of cardiovascular disease progression. Other compounds related to methionine metabolism have recently been identified as being involved in the risk of atherosclerosis and steatohepatitis. Indeed, the metabolism of sulfur amino acids has an impact on phosphatidylcholine (PC) metabolism, and anomalies in PC synthesis due to global hypomethylation have been associated with disturbances of lipid metabolism. In addition, impairment of H2S synthesis from cysteine favors atherosclerosis and steatosis in animal models. The effects of taurine on lipid metabolism appear heterogeneous depending on the populations of volunteers studied. A decrease in the concentration of intracellular glutathione, a tripeptide involved in redox homeostasis, is implicated in the etiology of cardiovascular diseases and steatosis. Last, supplementation with betaine, a compound that allows remethylation of homocysteine to methionine, decreases basal and methionine-stimulated homocysteinemia; however, it adversely increases plasma total and LDL cholesterol. The study of these metabolites may help determine the range of optimal and safe intakes of methionine and cysteine in dietary proteins and supplements. The amino acid requirement for protein synthesis in different situations and for optimal production of intracellular compounds involved in the regulation of lipid metabolism also needs to be considered for dietary attenuation of atherosclerosis and steatosis risk.

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To study, in young growing rats, the consequences of different levels of dietary protein deficiency on food intake, body weight, body composition, and energy balance and to assess the role of FGF21 in the adaptation to a low protein diet. Thirty-six weanling rats were fed diets containing 3%, 5%, 8%, 12%, 15% and 20% protein for three weeks. Body weight, food intake, energy expenditure and metabolic parameters were followed throughout this period. The very low-protein diets (3% and 5%) induced a large decrease in body weight gain and an increase in energy intake relative to body mass. No gain in fat mass was observed because energy expenditure increased in proportion to energy intake. As expected, Fgf21 expression in the liver and plasma FGF21 increased with low-protein diets, but Fgf21 expression in the hypothalamus decreased. Under low protein diets (3% and 5%), the increase in liver Fgf21 and the decrease of Fgf21 in the hypothalamus induced an increase in energy expenditure and the decrease in the satiety signal responsible for hyperphagia. Our results highlight that when dietary protein decreases below 8%, the liver detects the low protein diet and responds by activating synthesis and secretion of FGF21 in order to activate an endocrine signal that induces metabolic adaptation. The hypothalamus, in comparison, responds to protein deficiency when dietary protein decreases below 5%.

OBJECTIVES: In mice, low protein (LP) diets increase food intake (FI) thereby energy intake, to compensate for protein deficiency, but mice do not gain fat because total energy expenditure (TEE) is also increased. Fibroblast Growth Factor 21 (FGF21), which is expressed in the liver and in the brain, appears as a key player in these effects. The present study hypothesized that both LP diet but also only lysine or threonine deficiency can modulate FGF21 in the liver and in the hypothalamus that in turn is involved in the control of FI and energy expenditure. METHODS: Growing rats were fed for 3 weeks: i) LP diets containing 3-5-8-12-15 or 20% of milk protein, or ii) the same diets but supplemented with free amino acids at the level of the 20% protein diet except for lysine or threonine leading to lysine or threonine deficient diets. Body weight and FI were measured daily and energy expenditure were measured by indirect calorimetry. At the end of the experiment, rats were euthanized, tissues and biological fluids were removed and frozen, and body composition as well as gene expression and plasma FGF21 were analyzed. RESULTS: Diets with 3 and 5% protein, and diets highly deficient in lysine or threonine (85% and 75%) result in significant growth retardation. LP 3% and 5% induced an increase in relative FI. Surprisingly, an increase in TEE was observed under LP 5% protein, due to an increase in motor activity. Hepatic FGF21 expression is increased at 3 and 5% and strongly decreased at 12, 15 and 20% protein. In contrast, in the hypothalamus, FGF21 expression was significantly lower in LP 3% compared to a 20% protein diet, and for the other LP diets, the values are intermediate. Plasma FGF21 was higher in 3, 5, 8 and 12% protein than in 15 and 20% protein diets. Lysine or threonine deficiency were able to reproduce the effect of LP diet at 3 and 5% whereas at 8%, only the deficiency of threonine was able to reproduce the LP effect. CONCLUSIONS: These results showed that hepatic and hypothalamic expression FGF21 are inversely affected by protein deficiency. Such situations of deficiency induced an up-regulation of hepatic expression of FGF21 that increased TEE and a down-regulation of hypothalamic expression of FGF21 that could led to hyperphagia. Interestingly, the levels of FGF21 observed for the 3, 5, 8% protein diets could be due at least to lysine and threonine deficiency. FUNDING SOURCES: ABIES, AlimH department of INRAe.

International audience; Sphingolipids appear as a promising class of components susceptible to prevent the onset of the metabolic syndrome (MetS). Gut availability and effects of Camelina sativa sphingolipids were investigated in a mouse model of dietary-induced MetS. Seed meals from two Camelina sativa lines enriched, respectively, in C24-and C16-NH 2 − glycosyl-inositol-phosphoryl-ceramides (NH 2 GIPC) were used in hypercaloric diets. After 5 weeks on these two hypercaloric diets, two markers of the MetS were alleviated (adiposity and insulin resistance) as well as inflammation markers and colon barrier dysfunction. A more pronounced effect was observed with the C16-NH 2 GIPC-enriched HC diet, in particular for colon barrier function. Despite a lower digestibility, C16-NH 2 GIPC were more prevalent in the intestine wall. Sphingolipids provided as camelina meal can therefore counteract some deleterious effects of a hypercaloric diet in mice at the intestinal and systemic levels. Interestingly, these beneficial effects seem partly dependent on sphingolipid acyl chain length.

Introduction:The quality of dietary protein sources became a particularly sensitive issue in the current debates on a rebalancing between animal and vegetable food sources.The ability of a protein to meet the nutritional requirements of essential amino acid (EAA) is the basis for assessing the quality of protein.The objective of this study was to characterize the impact of lysine- and threonine-deficient gluten-based diets on the metabolism of growing rats and to identify molecular markers of these diets.Materials and Methods:Growing rats were fed for 3 weeks with a threonine-supplemented and 70% lysine-deficient gluten diet; a lysine-supplemented and 47% threonine-deficient gluten diet; a gluten diet supplemented in lysine and threonine to meet all the AA requirements, and a control diet with milk protein to meet all the AA requirements.Body weight and food intake were measured daily. At the end of the experiment, tissues and biological fluids were removed. The body composition was analyzed, gene expression measurements involved in protein and lipid metabolism were performed and the urinary metabolome was analyzed by LC-MS. Statistical analysis was done by variance analysis and metabolome analysis by discriminant analysis of independent components.Results:This EAA deficiency does not modify the food intake. Lysine deficiency induces a decrease in body weight gain, and lean body mass, associated with an increased in proteolysis and a decreased in proteosynthesis, a decreased in bone mineral density, and no effect on lipid metabolism.Threonine deficiency induces a decrease in body weight gain, and liver and skin weight, without changes in protein metabolism, bone mineral density, and lipid metabolism. After approval of the deficiency model, the metabolomic analysis performed on urine samples revealed the presence of specific discriminating molecules of the diets and types of proteins.Discussion:EAA deficiency has an impact on the growth, and bone and protein metabolism of growing rats. These deficiency states have resulted in different metabolome profiles that could lead to the identification of specific molecular markers of protein sources and related to EAA deficiencies.

In Western societies, unbalanced diets may lead to intestinal allostatic stress, with microbial dysbiosis and alteration of the gut barrier function. These local modifications may induce a low-grade inflammation via endotoxemic process, which contribute to systemic alterations clustering into the metabolic syndrome (MetS) and increasing the risk of cardiovascular diseases and type 2 diabetes. We investigated the sequence of events initiating the MetS in rats challenged with a diet that differed moderately from the dietary guidelines, regarding the proportions and nature of energy, carbohydrates, lipids and fibre.Male Wistar rats (265 g upon arrival) were with either a standard diet (Con, n = 10, 3730 kcalkg, 4.0% lipids, 6.3% sucrose, 58.0% starch, 5.0% fibre) or a westernized induction diet (Ind, n = 10, moderately enriched in energy (4120 kcal/kg), lipid (24.0%), and sugars (15%, half sucrose-half fructose), and low in starch (25.5%) and fibre (1.25%). An oral glucose tolerance test (OGTT) was performed after 3 weeks. Rats were euthanized after a further week for body composition and collection of caecum content and tissue samples. LPS-binding protein (LPS-BP) was assayed in plasma; ileum and colon samples were used for measurement of wall barrier function (using Ussing chambers) and microbial activity was assessed in caecum (enzymes and metabolites).Body weight did not differ between Con and Ind groups at any time, as well as the absolute masses and proportions of visceral adipose tissue and liver. Fasting triglyceride, glucose, insulin and LPS-BP concentrations, HOMA index and glucose AUC during the OGTT were similar in both groups. When compared to the Con group, Ind rats showed significantly higher risk markers, i.e.: (1) Insulin AUC (x2); (2) Hepatic triglyceride content (x2.8); (3) Wall permeability at both the para- and transcellular levels (x2.6 and 4.3, respectively) in the ileum (but not in the colon). In the caecum, H2S absolute and relative amounts were twice higher in the Ind group, in relation with 2–3-fold increases in specific and total activities of microbial cysteine desulfhydrase and proteases.Multiple dietary changes mimicking a moderately westernized diet induced an increased ileal permeability and changes in the caecal microbial activity, without evidence of endotoxemia. These perturbations were associated with detrimental rupture of homeostasis at both the splanchnic (hepatic steatosis) and systemic (insulin resistance) levels. In this realistic model, these alterations preceded the occurrence of clinical markers of the MetS (obesity and elevated plasma concentrations of glucose and triglyceride).

Sphingolipids appear as a promising class of components susceptible to prevent the onset of the metabolic syndrome (MetS). Gut availability and effects of

Introduction et but de l’etude Differentes etudes ont rapporte qu’une restriction proteique impacte le metabolisme energetique de rats en croissance. Une deficience severe en proteine (3 % ou 5 % du besoin) induit notamment une diminution du gain de poids corporel, une augmentation de la prise alimentaire relative, de la depense energetique, ainsi que des taux de fibroblast growth factor 21 (FGF21) plasmatiques. Cependant, l’implication precise de tous ou certains acides amines (AA) dans ces effets reste inconnue. Cette etude a pour objectif d’evaluer les effets d’une deficience en un AA strictement indispensable (lysine ou threonine ; AAI) sur le metabolisme energetique de rats en croissance. Materiel et methodes Des rats en croissance ont ete nourris avec des regimes deficients en lysine ou threonine pendant trois semaines : severement deficients (P3 L/T15 et P5 L/T25), moderement deficients (P8 L/T40 et P12 L/T60), controles (P15 L/T75 et P20 L/T100), excessif (P20 L/T170) ou un controle de l’effet des AA libres dans le regime (P3 L/T100). Le poids corporel et la prise alimentaire ont ete mesures quotidiennement, la depense energetique a ete evaluee par calorimetrie indirecte durant la troisieme semaine. A la fin de l’experimentation, les tissus et fluides biologiques ont ete preleves et la composition corporelle a ete analysee. L’analyse statistique a ete faite par modele mixte en mesure repetee et ANOVA a 1 facteur. Resultats et analyse statistique Les regimes severement deficients en lysine induisent une reduction du gain de poids corporel, des 3 et 6 jours (pour P3 L15 et P5 L25 respectivement). Pour la threonine, les regimes severement deficients, ainsi que le regime P8 T40, provoquent une diminution du gain de poids corporel des 1 et 6 jours. Parallelement, on observe une augmentation de la prise alimentaire relative (PAR) pour les regimes severement deficients en lysine et threonine, ainsi que pour les regimes P8 L40/P8 T40. Les regimes deficients en lysine n’influent pas sur la depense energetique de repos (DER) et le cout d’activite, et ne sont pas significativement differents des regimes controles pour la depense energetique totale (DET) et d’activite (DEA). Pour la deficience en threonine, on observe une diminution de la DET pour le regime P3 T15, confortee par une diminution de la DER, sans difference significative de la DEA par rapport aux regimes controles. De plus, le cout d’activite tend a etre diminue pour le regime P3 T15. Les deficiences severes en lysine ou threonine induisent une augmentation de FGF21 plasmatique. Conclusion La deficience en un AAI, lysine ou threonine, induit une diminution du gain de poids corporel chez le rat en croissance, malgre une PAR augmentee, avec un effet plus marque dans le cas de la threonine. Comparativement aux regimes controles, la deficience en lysine n’impacte pas la depense energetique, contrairement a la deficience en threonine qui entraine une diminution de la DET et de la DER.

Adequate protein intake during development is critical to ensure optimal bone gain and to attain a higher peak bone mass later. Using a mild protein restriction model in Balb/C mice consuming 6% of their total energy intake as soy protein (LP‐SOY)—for which we observed a significantly lower femoral cortical thickness, bone volume, trabecular number, and thickness reduction—we evaluated the effects of monosodium glutamate (MSG) supplementation at different concentrations (0.5, 1, 5, 10, and 20 g/kg of diet) on bone characteristics in LP‐SOY‐fed mice. After 6 and 12 weeks, LP‐SOY‐fed mice had lower BMD and reduced body weight related to lower lean mass, which was associated with a reduced IGF‐1 level. The negative effect of the LP‐SOY diet on BMD correlated with impaired bone formation. MSG supplementation, at 5, 10, and 20 g/kg of diet, and PTH injection, used as a positive control, were able to improve BMD and to increase osteoblast activity markers (P1NP and osteocalcin), as well as glutamine plasma concentration. An analysis of bone microarchitecture found that cortical bone was less sensitive to protein restriction than trabecular bone, and that MSG ingestion was able to preserve bone quality through an increase of collagen synthesis, although it did not allow normal bone growth. Our study reinforces the view that glutamate can act as a functional amino acid for bone physiology and support clinical investigation of glutamate supplementation in adults characterized by poor bone status, notably as a result of insufficient protein intake. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

International audience; BACKGROUNDMucosal healing has become a therapeutic goal to achieve stable remission in patients with inflammatory bowel diseases. To achieve this objective, overlapping actions of complex cellular processes, such as migration, proliferation, and differentiation, are required. These events are longitudinally and tightly controlled by numerous factors including a wide range of distinct regulatory proteins. However, the sequence of events associated with colon mucosal repair after colitis and the evolution of the luminal content characteristics during this process have been little studied.AIMTo document the evolution of colon mucosal characteristics during mucosal healing using a mouse model with chemically-induced colitis.METHODSC57BL/6 male mice were given 3.5% dextran sodium sulfate (DSS) in drinking water for 5 d. They were euthanized 2 (day 7), 5 (day 10), 8 (day 13), and 23 (day 28) d after DSS removal. The colonic luminal environment and epithelial repair processes during the inflammatory flare and colitis resolution were analyzed with reference to a non-DSS treated control group, euthanized at day 0. Epithelial repair events were assessed histo-morphologically in combination with functional permeability tests, expression of key inflammatory and repairing factors, and evaluation of colon mucosa-adherent microbiota composition by 16S rRNA sequencing.RESULTSThe maximal intensity of colitis was concomitant with maximal alterations of intestinal barrier function and histological damage associated with goblet cell depletion in colon mucosa. It was recorded 2 d after termination of the DSS-treatment, followed by a progressive return to values similar to those of control mice. Although signs of colitis were severe (inflammatory cell infiltrate, crypt disarray, increased permeability) and associated with colonic luminal alterations (hyperosmolarity, dysbiosis, decrease in short-chain fatty acid content), epithelial healing processes were launched early during the inflammatory flare with increased gene expression of certain key epithelial repair modulators, including transforming growth factor-β, interleukin (Il)-15, Il-22, Il-33, and serum amyloid A. Whereas signs of inflammation progressively diminished, luminal colonic environment alterations and microscopic abnormalities of colon mucosa persisted long after colitis induction.CONCLUSIONThis study shows that colon repair can be initiated in the context of inflamed mucosa associated with alterations of the luminal environment and highlights the longitudinal involvement of key modulators.

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International audience; Low-protein diets most often induce increased energy intake in an attempt to increase protein intake to meet protein needs with a risk of accumulation as fat of the excess energy intake. In female adult BALB/c mice, a decrease in dietary casein from 20% to 6% and 3% increased energy intake and slightly increased adiposity, and this response was exacerbated with soy proteins with low methionine content. The effect on fat mass was however limited because total energy expenditure increased to the same extent as energy intake. Lean body mass was preserved in all 6% fed mice and reduced only in 3% casein-fed animals. Insulin response to an oral glucose tolerance test was reduced in soy-fed mice and in low-protein-fed mice. Low-protein diets did not affect uncoupling protein 1 and increased fibroblast growth factor 21 (FGF21) in brown adipose tissue and increased FGF21, fatty acid synthase, and cluster of differentiation 36 in the liver. In the hypothalamus, neuropeptide Y was increased and proopiomelanocortin was decreased only in 3% casein-fed mice. In plasma, when protein was decreased, insulin-like growth factor-1 decreased and FGF21 increased and plasma FGF21 was best described by using a combination of dietary protein level, protein-to-carbohydrate ratio, and protein-to-methionine ratio in the diet. In conclusion, reducing dietary protein and protein quality increases energy intake but also energy expenditure resulting in an only slight increase in adiposity. In this process, FGF21 is probably an important signal that responds to a complex combination of protein restriction, protein quality, and carbohydrate content of the diet.

Diet of mothers during gestation may impact offspring phenotype. This study evaluated the consequences of a maternal High-Protein (HP) diet during gestation on food preferences and phenotypic characteristics in adult rat offspring. Dams were fed a HP or a Normal-Protein (NP) isocaloric diet during gestation only. Weaned female pups were divided into 3 diet groups: NP control or one of two dietary self-selection (DSS) conditions. In DSS1, offspring had a free choice between proteins (100%) or a mix of carbohydrates (88%) and lipids (12%). In DSS2, the choice was between proteins (100%), carbohydrate (100%) or lipids (100%). DSS2 groups consumed more of their energy from protein and lipids, with a decreased carbohydrate intake (p &lt, 0.0001) compared to NP groups, regardless of the maternal diet. Offspring from HP gestation dams fed the DSS2 diet (HPDSS2) had a 41.2% increase of total adiposity compared to NPDSS2 (p &lt, 0.03). Liver Insulin receptor and Insulin substrate receptor 1 expression was decreased in offspring from HP compared to NP gestation dams. These results showed the specific effects of DSS and maternal diet and data suggested that adult, female offspring exposed to a maternal HP diet during foetal life were more prone to adiposity development, in response to postweaning food conditions.

International audience; Mucosal healing after an inflammatory flare is associated with lasting clinical remission. The aim of the present work was to evaluate the impact of the amount of dietary protein on epithelial repair after an acute inflammatory episode. C57BL/6 DSS-treated mice received isocaloric diets with different levels of dietary protein 14% (P14), 30% (P30) and 53% (P53) for 3 (day 10), 6 (day 13) and 21 (day 28) days after the time of colitis maximal intensity. While the P53 diet worsened the DSS- induced inflammation both in intensity and duration, the P30 diet, when compared to the P14 diet, showed a beneficial effect during the epithelial repair process by accelerating inflammation resolution, reducing colonic permeability and increasing epithelial repair together with epithelial hyperproliferation. Dietary protein intake also impacted mucosa-adherent microbiota composition after inflammation since P30 fed mice showed increased colonization of butyrate-producing genera throughout the resolution phase. This study revealed that in our colitis model, the amount of protein in the diet modulated mucosal healing, with beneficial effects of a moderately high-protein diet, while very high-protein diet displayed deleterious effects on this process.

Discipline Experimental/mecanismes cellulaires et moleculaires Introduction et but de l’etude La qualite des sources alimentaires de proteines est devenue une question particulierement sensible dans le cadre des debats actuels sur un reequilibrage entre les sources alimentaires animales et vegetales. Les proteines sont un composant alimentaire indispensable a la survie, fournissant de l’azote et des acides amines (AA), et en particulier les neuf acides amines indispensables (AAI). En outre, parmi les AAI, la lysine et la threonine sont dits strictement indispensables car ne participant pas aux processus de transamination. La capacite d’une proteine a couvrir les besoins nutritionnels en AAI est a la base de l’evaluation de la qualite des sources alimentaires de proteines. L’objectif de cette etude etait de caracteriser l’impact de regimes a base de gluten deficients en lysine et en threonine sur le metabolisme de rats en croissance et d’identifier des biomarqueurs de ces regimes. L’hypothese est qu’un deficit en un AAI entraine une activation des systemes enzymatiques de catabolisme des autres AA, produisant des metabolites specifiques de ces degradations detectables dans les fluides biologiques et susceptibles de representer des biomarqueurs de tels regimes. Materiel et methodes Des rats en croissance ont ete nourris pendant 3 semaines avec un regime a base de gluten supplemente en threonine et deficient a 70% en lysine, un regime a base de gluten supplemente en lysine et deficient a 47% en threonine, un regime a base de gluten supplemente en lysine et en threonine couvrant 100% des besoins en tous les AA, et un regime temoin a base de proteine de lait couvrant 100% des besoins en tous les AA (APAFiS #5497). Le poids et la prise alimentaire ont ete mesures quotidiennement. A la fin de l’experience, les tissus et fluides biologiques ont ete preleves. La composition corporelle a ete analysee, des mesures d’expression de genes impliques dans le metabolisme proteique et lipidique ont ete realisees et le metabolome urinaire a ete analyse par LC-MS. L’analyse statistique a ete faite par analyse de variance et l’analyse des metabolomes par analyse discriminante des composants independants (IC-DA). Resultats et analyse statistique La deficience en ces AAI ne modifie pas la prise alimentaire. La deficience en lysine induit une diminution du gain de poids corporel, et de la masse maigre, en lien avec une augmentation de la proteolyse et une diminution de la proteosynthese, une diminution de la densite minerale osseuse, et aucun effet sur le metabolisme lipidique. La deficience en threonine, induit une diminution du gain de poids corporel, et du poids du foie et de la peau, sans modification du metabolisme proteique, de la densite minerale osseuse et metabolisme lipidique. Apres validation du modele de deficience, l’analyse metabolomique realisee sur des echantillons d’urine a mis en evidence la presence de molecules discriminantes specifiques des regimes et des types de proteines. Conclusion La deficience en un AAI a un impact sur la croissance et le metabolisme osseux et proteique de rats en croissance. Ces etats de deficience se sont traduits par des profils de metabolomes differents qui pourraient conduire a l’identification de biomarqueurs specifiques des sources de proteines et des deficiences associees en AAI.

International audience; Obesity is an increasing major public health concern asking for dietary strategies to limit weight gain and associated comorbidities. In this review, we present animal models, particularly rats and mice, which have been extensively used by scientists to understand the consequences of diet quality on weight gain and health. Notably, modulation of dietary protein quantity and/or quality has been shown to exert huge effects on body composition homeostasis through the modulation of food intake, energy expenditure, and metabolic pathways. Interestingly, the perinatal window appears to represent a critical period during which the protein intake of the dam can impact the offspring's weight gain and feeding behavior. Animal models are also widely used to understand the processes and mechanisms that contribute to obesity at different physiological and pathophysiological stages. An interesting example of such aspect is the situation of decreased estrogen level occurring at menopause, which is linked to weight gain and decreased energy expenditure. To study metabolic disorders associated with such situation, estrogen withdrawal in ovariectomized animal models to mimic menopause are frequently used. According to many studies, clear species-specific differences exist between rats and mice that need to be taken into account when results are extrapolated to humans.

Orexin-A and -B are hypothalamic neuropeptides of 33 and 28-amino acids, which regulate many homeostatic systems including sleep/wakefulness states, energy balance, energy homeostasis, reward seeking and drug addiction. Orexin-A treatment was also shown to reduce tumor development in xenografted nude mice and is thus a potential treatment for carcinogenesis. The aim of this work was to explore in healthy mice the consequences on energy expenditure components of an orexin-A treatment at a dose previously shown to be efficient to reduce tumor development. Physiological approaches were used to evaluate the effect of orexin-A on food intake pattern, energy metabolism body weight and body adiposity. Modulation of the expression of brain neuropeptides and receptors including NPY, POMC, AgRP, cocaine-and amphetamine related transcript (CART), corticotropin-releasing hormone (CRH) and prepro-orexin (HCRT), and Y-2 and Y-5 neuropeptide Y, MC4 (melanocortin), OX1 and OX2 orexin receptors (Y2R, Y5R, MC4R, OX1R and OX2R, respectively) was also explored. Our results show that orexin-A treatment does not significantly affect the components of energy expenditure, and glucose metabolism but reduces intraperitoneal fat deposit, adiposity and the expression of several brain neuropeptide receptors suggesting that peripheral orexin-A was able to reach the central nervous system. These findings establish that orexin-A treatment which is known for its activity as an inducer of tumor cell death, do have minor parallel consequence on energy homeostasis control.

OBJECTIVES: Low-protein diets are reported to induce hyperphagia to fulfil protein needs but at the expense of energy balance with a risk to gain in adiposity. However, different studies did not show body fat gain because an increased energy expenditure partly compensated the increase in energy intake and prevents the gain in adiposity. The present study evaluated in mice the consequence of protein restricted diets combined with protein quality (milk protein versus soy protein with slight methionine deficiency) on energy balance and adiposity and the role of FGF21 in the response to the protein restricted diets. METHODS: The study investigated in female BalbC mice the behavioural, metabolic and phenotypic responses to 8 weeks feeding a very low (3% energy - P3), moderately low (6% - P6) or adequate (20% - P20) dietary protein diet and evaluated if methionine scarcity, using soy protein (S) vs casein (C), affected these responses. Food intake, body weight, adiposity (assessed by DEXA), were measured throughout the study and body composition determined at the end of the study. Plasma, liver, muscle, adipose tissue and hypothalamus samples were collected for nutrient, hormones and gene expression measurements. RESULTS: Decreasing dietary casein from 20% to 3% increased energy intake, slightly increased adiposity, and this was exacerbated with methionine-deficient soy protein (figure 1). Lean body mass was reduced in 3% casein fed mice but preserved in all 6% fed mice. The effect on fat mass was limited because energy expenditure was also increased (figure 2). In plasma, low protein diets decreased IGF-1 and increased FGF21 that was related to protein level, protein to carbohydrate ratio and methionine content in the diet (figure 3). Insulin response to an oral glucose test was reduced in soy and low-protein fed mice. Low-protein diets did not affect Ucp1 but increased Fgf21 in brown adipose tissue and Fgf21, Fas, and Cd36 in the liver. In the hypothalamus, Npy was increased and Pomc was decreased only in 3% casein fed mice. CONCLUSIONS: Reducing dietary protein and protein quality increases both energy intake and energy expenditure resulting only in slight increase in adiposity. In this process FGF21 is probably a signal that responds to a combination of protein restriction and carbohydrate content of the diet. FUNDING SOURCES: Institut National de la Recherche Agronomique, AgroParisTech. SUPPORTING TABLES, IMAGES AND/OR GRAPHS

OBJECTIVES: Low protein diet and essential amino acid deficient-diet have an impact on body weight and growth and different studies also showed an impact of lysine intake on bone metabolism. Lysine has been shown to promote the absorption of intestinal calcium and to participate in the collagen synthesis through its involvement in the reticulation process of the tropocollagen beams. The assembly of tropocollagen bundle into mature collagen fibers is essential for bone formation and remodeling (civitelli et al, 1992; Fini et al, 2001). The objective of this study was to characterize the impact of low protein diet and lysine-deficient diet on bone metabolism of growing rats. METHODS: Study 1: 6 group of growing rats were fed for 3 weeks different diet with different content of milk protein at levels of 3%, 5%, 8%, 12%, 15% or 20% (% total energy). Study 2: 7 group of growing rats were fed diets with different lysine content (as % of lysine requirement), for 3 weeks: 15%, 25%, 40%, 60%, 75%, 100% or 170% (% Lysine requirement). Body weight was measured daily. At the end of the experiment, the body composition was analyzed and tissues were removed for measurements of the expression of genes involved in protein and bone metabolism. Statistical analysis was done by variance analysis. RESULTS: Rats fed low protein diet (3% and 5% of milk protein), compared to control have a lower growth, with a lower body weight and naso-anal length. This weak growth was associated with a lower lean body mass, and also had an impact on bone metabolism. There was a decrease in the bone mineral density, bone mineral content and femur size, associated with a decrease of markers of bone turnover and formation. The same results on bone metabolism were observed on rats fed the 85% lysine deficient diet. CONCLUSIONS: Low protein diet and lysine-deficient diet reduce growth and bone metabolism. The impact of low protein diet could be related to the lysine deficiency, which have an impact on the calcium intestinal absorption and on collagen synthesis. FUNDING SOURCES: INRA, AgroParisTech. Supporting Tables, Images and/or Graphs

WOS:000375891000010; International audience; To prevent the development of adiposity-associated metabolic diseases, early biomarkers are needed. Such markers could bring insight to understand the complexity of susceptibility to obesity. Urine and plasma metabolomics fingerprints have been successfully associated with metabolic dysfunctions. Fat resistance (FR) was found to be associated with higher urinary levels of acylglycines and leucine. However, no differences were observed before the diet switch. In this context, we aimed at characterizing metabolic signatures predictive of resistance or sensitivity to fat in the C57Bl6/J mouse model. Urinary metabolic profiles of FR (n = 15) and fat sensitivity (FS) mice (n = 14) were performed on liquid chromatography mass spectrometry. Urinary and plasma metabolic profiles were first collected at baseline (during low-fat diet), then after 10 weeks of high-fat (HF) feeding. Mice were sorted a posteriori into FS and FR based on their final adiposity. After HF feeding for 10 weeks, FS mice tended to have lower plasma levels of p-hydroxybutyrate than FR ones. Urinary metabolic profiles showed that baseline levels of octanoylglycine, leucine and valine were significantly lower in FS mice. Moreover, expressions in the adipose tissue of Baat and Glyat mRNA were lower in FS than in FR mice. In muscle, mRNA encoding CaD and UbE2b tended to be lower in FS mice than in FR mice (P=.056 and P=.071, respectively). The data show that lower levels of urinary octanoylglycine, leucine and valine are potential predictive biomarkers of FS and could be related to a lower stimulation in adipose acyl-coenzyme A conjugation to glycine and to muscle protein breakdown. (C) 2016 Elsevier Inc. All rights reserved.

Nutritional approaches may help to preserve bone quality. The purpose of our study was to demonstrate the efficiency of an innovative bone health product (BHP) including micellar casein rich in calcium, vitamin D2 and vitamin K2, to improve bone mineral density. The aim of postmenopausal osteoporosis treatment is to decrease bone resorption and/or increase bone formation. Because of the slow bone turnover, osteoporosis prevention and therapies are long-lasting, implying great costs and poor compliance. Even if the effects of nutrition on bone are not as marked as that of pharmaceutical agents, it can be of great help. The purpose of our study was to demonstrate the efficiency of an innovative bone health product (BHP) containing micellar casein rich in calcium, vitamin D2 and vitamin K2, for the improvement of bone mineral density (BMD). An ovariectomized mice model was used to study the effect of different concentrations of the ingredient on BMD and microarchitectural parameters. Blood concentrations of C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type 1 procollagene (PINP), alkaline phosphatase (ALP), osteocalcin (OC) and RANKL were also measured to evaluate bone remodelling, To evaluate the efficiency of the product to modulate osteoblast and osteoclast growth and differentiation, primary murine bone cells were used. In vivo studies showed that BMD and microarchitectural parameters were dose-dependently improved after ingestion of the supplement for 3 months. We also report increased osteoblast activity as shown by increased OC activity and decreased osteoclastogenesis as shown by reduced CTX activity. In vitro studies support that BHPs stimulate osteoblast differentiation and mineralization and inhibit osteoclast resorption activity. Our results show that, when chronically ingested, BHPs improve BMD of ovariectomized mice. This work supports that providing an ingredient including micellar casein rich in calcium, vitamin D2 and vitamin K2 is more efficient than the control diet to maintain bone quality.

We have previously shown that bovine lactoferrin (bLF) supplementation can have a beneficial effect on postmenopausal bone loss by modulating bone formation and resorption. A direct effect of bLF on bone metabolism is support by its presence in mice blood. Moreover we know that LF plays a key role in innate immunity and recent studies have shown its ability to modulate adaptive immunity. In particular bLF ingestion prevents recruitment and activation of immune cells at inflammatory sites. We propose that LF through its ability to modulate maturation and differentiation of leucocytes can participate to abolish the deregulation induced by estrogen deficiency on T cells. This study evaluated the effects of bovine lactoferrin on immune function in ovariectomized mice. We investigated whether bLF ingestion could prevent bone loss via modulation of immune function. Three-month-old female C3H mice were either ovariectomized or sham-operated and fed for 1, 2 or 4 months with a control diet (AIN-93M) or the same diet including 10g bLF/kg diet. Bone mineral density was determined using a Lunar Piximus densitometer. The immune parameters were assessed by flow cytometry. In addition, Real-Time PCR was performed to quantify TNFα expression and plasma cytokines were measured at 4 months with Luminex. Ovariectomy induced significant changes on bone parameters and increased recruitment of macrophages, dendritic cells, and B and T cells associated with T lymphocyte activation in bone marrow. Compared to the control diet, ingestion of bLF-enriched diet for 2 months prevented T cell activation and restored dendritic and B cell populations in the bone micro-environment in ovariectomized mice. Furthermore, TNFα expression in bone was decreased by bLF supplementation after 2 and 4 months. Similarly, a decreased plasma level of TNFα was observed concomitantly to an increase of IL-10 level. In conclusion, these experiments suggest that bLF can mediate the prevention of lymphocyte activation and cytokine release in the bone micro-environment. Dietary bLF supplementation could have a beneficial effect on postmenopausal bone loss by modulating immune function.

Introduction et but de l’etude Depuis peu, la cicatrisation complete de la muqueuse intestinale est consideree comme un objectif therapeutique pour la prevention des complications associees aux maladies inflammatoires chroniques de l’intestin. Cependant, le role de l’apport proteique alimentaire et les besoins proteiques necessaires a la cicatrisation muqueuse ont ete peu etudies. Le but de cette l’etude est de tester l’effet de differents niveaux d’apport proteique sur la reparation epitheliale apres un episode inflammatoire colique aigu. Materiel et methodes Des souris C57BL/6 traitees avec du dextran sulfate de sodium (DSS, 3,5 %, 5 jours) ont ete reparties en 3 groupes a j7, recevant un regime isocalorique dont le niveau en proteines varie : 14, 30 et 53 % pendant 3 (j10), 6 (j13) et 21 (j28) jours. Une etude de suivi ainsi que des analyses biochimiques, histologiques, transcriptionnelles et du microbiote associe a la muqueuse ont ete realisees. Resultats et analyse statistique Le score inflammatoire est plus eleve de j9 a j22 chez les animaux sous regime P53 vs P14 et P30 (p Conclusion L’ingestion de proteines alimentaires module differenciellement la resolution de la colite chimio-induite selon le niveau d’apport. Notre etude revele qu’un regime moderement eleve en proteines (P30) favorise la reparation epitheliale en limitant l’inflammation, en renforcant la fonction barriere et en contribuant a restaurer la composition du microbiote apres dysbiose.

Galacto-oligosaccharides (GOS) are non-digestible oligosaccharides with short galactosyl chain units produced by lactose fermentation which are considered as prebiotics. Only few studies have investigated the effects of GOS medium-term ingestion on the small intestinal epithelium characteristics. In this study, we evaluated the consequences of GOS ingestion on small intestinal mucosal morphology, on brush-border membrane enzyme activities and on mucin content in BALB/c mice. Mice received the experimental diets for 4 weeks and then the small intestine was collected to measure sucrase, lactase and alkaline phosphatase activities, to study the villus heights in the jejunum mucosa and to determine mucosal mucin content as well as MUC-2 and MUC-4 mRNAs expression by qRT-PCR. Our results showed that GOS has no detectable effect on the intestine villus height but increased the total protein content by twofold. Sucrase activity was significantly increased in the intestinal mucosa recovered from animals fed the GOS diet without any detectable modification of lactase and phosphatase activities. Interestingly, GOS was also able to increase sucrase activity in cultured Caco-2 cells raising the view that they likely act directly on these cells. Furthermore, GOS was found to markedly increase O-linked glycoproteins associated with the intestinal mucosa without modifying MUC-2, MUC-4 mRNAs expression. Lastly, TNF-α mRNA expression was also not modified after GOS ingestion. These results suggest that, in BALB/c mice, 4-week GOS ingestion is able to increase the small intestinal mucosa-associated mucin content and enterocyte-associated sucrase activity without modifying villus height.

The aim of the present study was to evaluate the effect of dietary lactoferrin on bone metabolism in vivo using a postmenopausal animal model. We investigated whether bovine lactoferrin (bLF) ingestion could prevent bone loss in ovariectomized mice. Twelve-week-old female C3H mice either ovariectomized or sham operated were fed for 27 wk with the control diet (AIN-93M with 140 g of total milk protein as a protein source per kg of diet). Four groups of ovariectomized mice received diets including different concentrations of bLF (1, 5, 10, or 20 g of total milk protein were replaced by bLF). Ovariectomy induced a decreased uterine weight and a smaller gain of bone mineral density. Immunoreactive bLF was detected in the peripheral blood, and its concentration was related to the amount of bLF ingestion. bLF supplementation to the diet improved bone mineral density (BMD) and femoral failure load in a dose-dependent manner. We confirmed the direct effects of bLF in vitro using established and primary cultures of murine bone cells. Addition of bLF to the culture medium at a concentration of between 1 and 1,000 μg/ml stimulated both cell growth and differentiation of osteoblastic MC3T3 cells while inhibiting the growth of preosteoclastic RAW 267.4 cells. In primary culture of mixed bone cells, an enhanced osteoblast differentiation was associated with an inhibition of osteoclast differentiation at lower bLF concentrations (1–10 μg/ml). In conclusion, these findings suggest that dietary lactoferrin supplementation can have a beneficial effect on postmenopausal bone loss by modulating bone formation and resorption.

Lactoferrin is a glycoprotein with antimicrobial and immunoregulatory properties, which is found in milk, other external secretions, and in the secondary granules of neutrophils. The present study examined the time course of uptake and the pattern of tissue accumulation of bovine lactoferrin (bLf) following intragastric intubation of a single dose to adult naïve mice or to mice daily fed bLf for 4 weeks. Following ingestion, bLf was transferred from the intestine into peripheral blood in a form with intact molecular weight (80 kDa) and localized within 10 to 20 min after oral administration in the liver, kidneys, gall bladder, spleen, and brain of both groups of mice. Immunoreactive bLf could also be detected in the luminal contents of the stomach, small intestine and colon 1 h after intragastric intubation. Interestingly, serum and tissue accumulation of bLf was approximately 50% lower in mice chronically fed this protein than in those given only the single oral dose. Furthermore, significant levels of bLf-specific IgA and IgG antibodies as well as bLf-containing IgA- and IgG immune complexes were detected in mice chronically fed bLf but not in those fed only once. Taken together, these results indicate that bLf resists major proteolytic degradation in the intestinal lumen and is readily absorbed in an antigenic form in blood and various mouse tissues. Chronic ingestion of lactoferrin reduces its uptake, probably through mechanisms such as immune exclusion, which minimize potential harmful reactions to food products.

Omnivores show recognition of essential (indispensable) amino acid deficiency by changing their feeding behavior within 20 min, yet the cellular mechanisms of amino acid sensation in eukaryotes are poorly understood. The anterior piriform cortex (APC) of the brain in rats or its analog in birds likely houses the in vivo amino acid chemosensor. Because amino acid transporters adapt rapidly to essential amino acid deficiency in several cell models, we hypothesized that activation of electrogenic amino acid transport in APC neurons might contribute to the function of the amino acid sensor. We evaluated transport systems in primary cultures of neurons from the APC, hippocampus and cerebellum, or glia, incubated in complete or threonine-devoid (deficient) medium. After 10 min in deficient medium, uptake of threonine or a system A-selective substrate, methyl amino-isobutyric acid, was increased 60% in APC neurons only (P < 0.05). These results demonstrated upregulation of system A, an electrogenic amino acid-sodium symporter. This depletion-induced activation required sodium, intact intracellular trafficking, and phosphorylation of signal transduction-related kinases. Efflux studies showed that other transporter types were functional in the APC; they appeared to be altered dynamically in threonine-deficient cells in response to rapid increases in system A activity. The present data provided support for the chemical sensitivity of the APC and its role as the brain area housing the indispensable amino acid chemosensor. They also showed a region-specific, phosphorylation-dependent activation of the system A transporter in the brain in response to threonine deficiency.

This study was designed to analyse the effects of human (h) and bovine lactoferrin (bLF) on the growth and differentiation of intestinal cells using the mice model supplemented with Lactoferrin (LF) and the enterocyte-like model of Caco-2 cells which spontaneously differentiate after confluency. In mice, bLF supplementation increased jejunal villus height and the expression of several intestinal brush border membrane enzymes activities. Addition of bLF or hLF to undifferentiated Caco-2 cells was able to increase cell proliferation with confluency being reached more rapidly. Moreover, when Caco-2 cells were grown in the presence of LF for 3 weeks, brush-border membrane-associated enzyme activities i.e. sucrase, alkaline phosphatase and neutral aminopeptidase, as well as the l-glutamate transporter expression were all increased indicating an increased Caco-2 cell differentiation. Accordingly, cDNA Atlas array and Western blot analysis of cell cycle proteins shown a decreased expression of Cdck2 and an increased TAF1 expression; these proteins being implicated in the regulation of numerous genes related to cellular proliferation and differentiation. These modifications were associated with an inhibition of Caco-2 cell spontaneous apoptosis. Altogether, our results indicate that LF increase in vivo and in vitro enterocyte differentiation. In addition, LF was found to increase in vitro enterocyte proliferation resulting in higher cell density in cell flasks, an effect that was likely partly due to a reduction of the cellular apoptosis. The different stimulation patterns observed for the different parameters associated with cell differentiation in relationship with specific gene regulation is discussed.

Adequate protein intake during development is critical to ensure optimal bone gain and to attain a higher peak bone mass later on. We hypothesized that the quality of the dietary protein is of prime importance for bone physiology during moderate protein restriction. The target population was growing Balb/C mice. We compared two protein restricted diets (6% of total energy as protein), one based on soy (LP-SOY) and one based on casein (LP-CAS). For comparison, a normal protein soy-based control group (NP-SOY) and a low protein group receiving an anabolic daily parathyroid hormone (PTH) 1-34 injection (LP-SOY + PTH) were included in the protocol. After 8 weeks, LP-SOY mice had reduced body weights related to a lower lean mass whereas LP-CAS mice were not different from the NP-SOY group. LP-SOY mice were characterized by lower femoral cortical thickness, bone volume, trabecular number and thickness and increased medullar adiposity when compared to both the LP-CAS and NP-SOY groups. However, the dietary intervention had no effect on the vertebral parameters. The negative effect of the LP-SOY diet was correlated to an impaired bone formation as shown by the reduced P1NP serum level as well as the reduced osteoid surfaces and bone formation rate in the femur. PTH injection in LP-SOY mice had no effect on total weight or lean mass, but improved all bone parameters at both femoral and vertebral sites, suggesting that amino acid deficiency was not the primary reason for degraded bone status in mice consuming soy protein. In conclusion, our study showed that under the same protein restriction (6% of energy), a soy diet leads to impaired bone health whereas a casein diet has little effect when compared to a normal protein control. (C) 2013 Elsevier Inc. All rights reserved.

Introduction et but de l’etude Les orexines ou hypocretines 1 et 2, via la stimulation des recepteurs aux orexines 1 (OX1R) et 2 (OX2R), jouent un role non seulement dans la regulation des phases d’eveil et de sommeil, de la prise alimentaire, du controle du poids et de la depense energetique mais egalement stimulent l’apoptose des cellules cancereuses. Voisin et al. (2011) ont montre que les recepteurs OX1R sont specifiquement exprimes dans les cellules cancereuses du colon, les cellules saines adjacentes n’exprimant pas ce recepteur. Ces travaux suggerent que les orexines pourraient etre un traitement prometteur de certains types de cancer. Connaissant l’implication des orexines dans de nombreuses fonctions physiologiques et en particulier dans le controle de la prise alimentaire il semblait indispensable de verifier les consequences d’un traitement chronique aux orexines sur ces fonctions avant d’envisager une approche therapeutique. Materiel et methodes Notre etude incluait deux groupes de souris Balb/c qui ont recu soit des injections avec le vehicule (groupe temoin) ou avec l’orexine A (1 μmole/kg) pendant 6 semaines. Les animaux ont ete peses quotidiennement. Les sequences de prise alimentaires alimentaire ont ete etudiees au cours de la derniere semaine par enregistrement sur 24 h et un test de tolerance au glucose a ete effectue avant le sacrifice des animaux. A la fin de l’etude les compositions corporelles ont ete mesurees par dissection et pesee des principaux organes et depots adipeux. L’expression hypothalamique des neuropeptides et des recepteurs a ete quantifiee par PCR en temps reel. Resultats Nos travaux montrent qu’un traitement chronique avec une dose d’orexine capable d’induire l’apoptose des cellules cancereuses, est capable de reduire au niveau du cerveau l’expression du recepteur (OX1R) et d’induire une legere diminution du tissu adipeux. Cependant ce traitement n’a pas d’impact sur la prise de poids des animaux, ni sur le metabolisme glucidique. Concernant la prise alimentaire seule la vitesse d’ingestion de la nourriture augmente significativement mais pas la quantite ingeree. Conclusion A une concentration efficace pour induire l’apoptose des cellules cancereuses nous n’observons pas de modifications du comportement alimentaire ni de la prise de poids des animaux apres 6 semaines de traitement.

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Dietary proteins represent 10 to 20% of energy consumption. The recommended daily minimum intake of protein and amino acids in adults is 0.8 g per kg of body weight. However, no upper limit has been identified. In industrialized countries, the main sources of protein are milk, eggs and meat. The nutritional value of protein is influenced by several factors, especially the amino acid (AA) composition, protein digestibility, protein digestion kinetics and the ability to transfer AA for protein synthesis. Diets based on either animal or vegetable products supply proteins of differing quality in differing quantities. Plant proteins are often deficient or low in some specific indispensable AAs. Soy protein is reported as a “complete” protein but its overall indispensable AA content is relatively low (~85% lower than milk) (Wilson & Wilson, 2006).

International audience; This study evaluates the effect of hydrolyzed collagen (HC) on bone health of ovariectomized mice (OVX) at different ages. Twenty-six weeks after the OVX procedure, HC ingestion was still able to improve significantly bone mineral density (BMD) and some femur biomechanical parameters. Moreover, HC ingestion for 1 month before surgery prevented BMD decrease. HC can play an important role in preserving BMD before osteoporosis appears. The aim of this study was to evaluate the effect of HC on bone health of ovariectomized mice at different ages. Female C3H mice were either OVX at 3 or 6 months and fed for 6 months (first experiment) or 3 months (second experiment) with diet including 0, 10, or 25 g/kg of HC. In the second experiment, one group received HC 1 month before surgery, and two groups received the supplementation immediately after surgery, one fed ad libitum and the other by gavage. Mice treated with raloxifene were used as a positive control. BMD, femur intrinsic and extrinsic biomechanical properties, and type I collagen C-terminal telopeptide were measured after 12 and 26 weeks. Food intake and spontaneous physical activity were also recorded. The OVX procedure increased body weight, while food intake decreased, thus suggesting that resting metabolism was decreased. Ingestion of 25 g/kg of HC for 3 or 6 months reduced bone loss significantly in, respectively, 3- and 6-month-old OVX mice. The lowest HC concentration was less efficient. HC ingestion for 3 months is as efficient as raloxifene to protect 3-month-old OVX mice from bone loss. Our results also demonstrated that HC ingestion before surgery prevented the BMD decreases. This study confirms that dietary collagen reduces bone loss in OVX mice by increasing the diameter of the cortical areas of femurs and can have a preventive effect.