L’activité physique spontanée en condition d’obésité ralentit la croissance tumorale en modulant les signaux hormonaux tissulaires

Nutrition en pathologie : cancer, insuffisance d’organes, réanimation, pathologies digestives…COMMUNICATIONS AFFICHEESIntroduction et but de l’étude: En situation d’obésité, les dérégulations du tissu adipeux induisent la sécrétion d’œstradiol et de leptine (pro-inflammatoire) aux dépens d'adiponectine (anti-inflammatoire), une augmentation du stress oxydant associée à une baisse des capacités anti-oxydantes favorisant un microenvironnement pro-carcinogène. L’activité physique (AP), facteur de prévention de l’obésité et des cancers, favorise une inflammation aigüe modérée, la réponse anti-oxydante et la sécrétion d’adipokines anti-inflammatoires. Les mécanismes de protection de l’AP dans le cancer mammaire sont mal connus. Le but est de caractériser le dialogue inter-organe induit par l’AP spontanée et l’impact sur la croissance tumorale dans un modèle de carcinogenèse mammaire murin en situation d’obésité.Matériel et méthodes: Des souris C57BL/6 âgées (n=10/groupe), ovariectomisées, nourries avec un régime hyper-lipidique, sont hébergées en environnement standard (ES) ou en environnement enrichi (EE) favorisant l’AP spontanée. Après 4 semaines, des cellules tumorales syngéniques EO771 sont implantées par fat-pad. Au sacrifice, l’exploration des adipokines et des cytokines a été conduite dans les organes d’intérêt (tumeur, tissu adipeux inguinal, gastrocnémien, plasma) ainsi que la caractérisation du statut oxydatif et des voies de signalisation (JNK, AKT, NFκB, p38, S6K1) de la tumeur.Résultats et Analyse statistique : L’EE entraîne une augmentation de l’AP sans modification des masses maigres et adipeuses, ni des métabolites énergétiques (triglycérides, glucose). L’analyse factorielle multiple montre que les variables expliquant les différences entre individus sont les masses adipeuses (totale, viscérale et inguinale), l’adiponectine plasmatique, les taux de leptine des tissus d’intérêt, les capacités anti-oxydantes et les voies de signalisation intra-tumorales. Les adipokines plasmatiques sont corrélées aux masses adipeuses et aux voies de signalisation tumorales. Le taux de leptine dans le gastrocnémien est corrélé avec celui de la tumeur (r²=0,57 p<0,05) et montre une forte diminution chez les animaux EE vs ES (tumeur : 0,30 ± 0,07 vs 0,60 ± 0,10 pg/mg ; p<0,05 ; gastrocnémien : 0,09 ± 0,03 vs 0,45 ± 0,11 pg/mg ; p<0,05). L’IL6 plasmatique est diminuée et associée à une réduction du stress oxydant tumoral (thiols protéiques, GST, thiorédoxine) pour les souris EE vs ES. Une baisse de l’activation des voies tumorales de signalisation est observée pour les souris EE vs ES, corrélée positivement avec les masses musculaires et négativement avec les masses adipeuses.Conclusion: Ces résultats montrent que l'activité physique spontanée en condition d’obésité ralentie la croissance tumorale, en modifiant le dialogue inter-organe, conduisant à une réduction de l’inflammation et du stress oxydatif du microenvironnement tumoral. Une consommation de la leptine est observée dans la tumeur et le gastrocnémien alors que la production au niveau du tissu adipeux et la distribution plasmatique ne semblent pas affectées. Ainsi, l’activité physique module les signaux hormonaux tissulaires conduisant à une moindre stimulation des voies de signalisation nécessaires à la croissance tumorale

L-Arginine supplementation prevents allodynia and hyperalgesia in painful diabetic neuropathic rats by normalizing plasma nitric oxide concentration and increasing plasma agmatine concentration

Neuropathic pain is a common diabetic complication. It is characterized by symptoms of spontaneous and stimulus-evoked pain including hyperalgesia and allodynia. L-Arginine is a common precursor of many metabolites of biological interest, in particular, nitric oxide (NO), ornithine, and hence polyamines. In central nervous system, NO, glutamate, and polyamines share an N-methyl-D-aspartate (NMDA) receptor-mediated effect. We hypothesized that a variation in arginine metabolism caused by diabetes may contribute to development and maintenance of neuropathic pain and to the worsening of clinical and biological signs of diabetes.We examined whether oral L-arginine supplementation (2.58 ± 0.13 g/l in drinking water for 3 weeks) could improve the development of neuropathic pain and the clinical, biological, and metabolic complications of diabetes in streptozocin (STZ)-induced diabetic (D) rats.STZ administration induced classical symptoms of type 1 diabetes. Diabetic rats also displayed mechanical hypersensitivity, tactile, and thermal allodynia. Plasma citrulline and NO levels were increased in diabetic hyperalgesic/allodynic rats. L-Arginine supplementation failed to reduce hyperglycaemia, polyphagia, and weight loss. Moreover, it abolished hyperalgesia and allodynia by normalizing NO plasma concentration and increasing plasma agmatine concentration.L-Arginine supplementation prevented the development of mechanical hyperalgesia, tactile, and thermal allodynia in painful diabetic neuropathy with concomitant reduction of NO and increased agmatine production, offering new therapeutic opportunities for the management of diabetic neuropathic pain

Age-related change in the retinoid X receptor beta gene expression in peripheral blood mononuclear cells of healthy volunteers : Effect of 13-cis retinoic acid supplementation

International audienceThe regulation of cell growth and differentiation and also expression of a number of genes by retinoids are mediated by nuclear retinoid receptors (RARs and/or RXRs). In this study we investigated age-related alteration in both RAR and RXR receptor subtypes gene expression and tissue transglutaminase (tTG) activity before and after supplementation with 13-cis retinoic acid (13cRA) in human peripheral blood mononuclear cells (PBMCs). Healthy men (40) were divided in two groups according to their age (young group: 26.1 +/- 4.1 years and old group: 65.4 +/- 3.8 years). Each volunteer received 13cRA (Curacne (R), 0.5 mg/(kg day)) during a period of 4 weeks. We have shown that RXR beta expression was decreased significantly (p = 0.0108) in PBMCs of elderly men when compared to that of young volunteers. Distribution of retinoic acid receptor subtype expression in PBMCs was found in the order: RXRP > RAR gamma > RXR alpha > RAR alpha. The tTG activity in PBMCs reflected a trend to be enhanced after 13-cis retinoic acid supplementation. In conclusion, we demonstrate a significant decrease in the expression of RXRP subtype of rexinoid receptors in PBMCs of healthy elderly men. Our data suggest that in healthy elderly men reduction of RXRP expression in PBMCs might be a common feature of physiological senescence

Increased consumption of salmon during pregnancy partly prevents the decline of some plasma essential amino acid concentrations in pregnant women

International audienceBackground & aims: Oily fish is a good source of n-3 long-chain polyunsaturated fatty acids. Since these fatty acids may change efficiency of amino acid (AA) absorption, we determined whether increased salmon consumption influences plasma AA concentrations in pregnant women and their newborns. Methods: Pregnant women were randomly allocated to remain on their habitual diet (n = 61; control group) or to consume two 150 g farmed salmon portions per week from 20 weeks pregnancy until birth (n = 62; salmon group). Plasma AA concentrations were determined in women at w20, w34 and w38 of pregnancy and in umbilical cord at delivery. Results: Concentrations of arginine, valine, leucine and lysine were affected by both time of pregnancy and salmon intake (p 0.05). Conclusions: Two portions/wk of oily fish increased plasma essential AA concentrations during pregnancy and could contribute to a maternal health benefit. Two portions/wk of salmon did not affect plasma AA concentrations in the newborn. (C) 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved

Does consumption of two portions of salmon per week enhance the antioxidant defense system in pregnant women?

Salmon is a rich source of marine n-3 fatty acids, which may increase oxidative stress and, in turn, could affect the antioxidant defense system in blood plasma and erythrocytes of pregnant women. The Salmon in Pregnancy Study provided two meals of salmon per week to pregnant women from week 20 of gestation; the control group maintained their habitual diet low in oily fish. Higher selenium and retinol plasma concentrations were observed after dietary salmon supplementation. Besides, a concomitant increase in selenium and glutathione concentration as well as glutathione peroxidase and reductase activities were detected as pregnancy progressed. However, tocopherols, retinol, ?-carotene, and coenzyme Q10 decreased in late pregnancy. Collectively, our findings lead to the hypothesis that increased farmed salmon intake may increase antioxidant defenses during pregnancy