Natural isotopic signatures of variations in nitrogen metabolism during under- or over-nutrition.

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Plasma asymmetric and symmetric dimethylarginine in a rat model of endothelial dysfunction induced by acute hyperhomocysteinemia

Hyperhomocysteinemia induces vascular endothelial dysfunction, an early hallmark of atherogenesis. While higher levels of circulating asymmetric dimethylarginine (ADMA) and symmetric dimethyl arginine (SDMA), endogenous inhibitors of nitric oxide synthesis, have been associated with increased cardiovascular risk, the role that ADMA and SDMA play in the initiation of hyperhomocysteinemia-induced endothelial dysfunction remains still controversial. In the present study, we studied the changes of circulating ADMA and SDMA in a rat model of acutely hyperhomocysteinemia-induced endothelial dysfunction. In healthy rats, endothelium-related vascular reactivity (measured as acetylcholine-induced transient decrease in mean arterial blood pressure), plasma ADMA and SDMA, total plasma homocysteine (tHcy), cysteine and glutathione were measured before and 2, 4 and 6 h after methionine loading or vehicle. mRNA expression of hepatic dimethylarginine dimethylaminohydrolase-1 (DDAH1), a key protein responsible for ADMA metabolism, was measured 6 h after the methionine loading or the vehicle. Expectedly, methionine load induced a sustained increase in tHcy (up to 54.9 +/- A 1.9 A mu M) and a 30 % decrease in vascular reactivity compared to the baseline values. Plasma ADMA and SDMA decreased transiently after the methionine load. Hepatic mRNA expression of DDAH1, cathepsin D, and ubiquitin were significantly lower 6 h after the methionine load than after the vehicle. The absence of an elevation of circulating ADMA and SDMA in this model suggests that endothelial dysfunction induced by acute hyperhomocysteinemia cannot be explained by an up-regulation of protein arginine methyltransferases or a down-regulation of DDAH1. In experimental endothelial dysfunction induced by acute hyperhomocysteinemia, down-regulation of the proteasome is likely to dampen the release of ADMA and SDMA in the circulation

A long-term high-protein diet markedly reduces adipose tissue without major side effects in Wistar male rats

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La sensibilité à l'induction de l'obésité et du syndrome métabolique par un régime gras et sucré s'accompagne d'une efficacité protéique accrue dans le foie et diminuée dans le muscle

International audienceIntroduction et but de l’étude : Il existe une forte variabilité interindividuelle de réponse à une alimentation trop grasse etsucrée : chez les individus les moins aptes à gérer cet excès chronique d'énergie, elle favorise le développement d'uneobésité (O) parfois associée à un syndrome métabolique (SM), avec des altérations du métabolisme énergétique maisaussi probablement du métabolisme protéique qui sont encore mal connues. Cette étude visait à mieux identifier lavariabilité de réponse à un régime gras et sucré ainsi que les différences métaboliques entre individus sensibles etrésistants à l'O et au SM, en utilisant des biomarqueurs isotopiques des orientations préférentielles du métabolismeprotéique, les abondances naturelles en 15N (δ15N) des tissus.Matériel et méthodes : 36 rats Wistar mâles, de poids initialement similaires, ont été nourris avec un régime riche enlipides et sucres, suivis pour leurs consommation et gain de poids pendant 4 mois puis euthanasiés pour mesurerparamètres biochimiques, composition corporelle et δ15N des protéines tissulaires par spectrométrie de masse à ratioisotopique. Nous avons discriminé les rats selon leur sensibilité à l'O et au SM par une classification non supervisée(proc cluster sous SAS), sur la base de 2 indicateurs d'O (poids et adiposité viscérale) et de 2 indicateurs de SM (HOMAIRet triglycérides hépatiques). Nous avons calculé le Zscore global d'O et de SM (ZOSM) comme la moyenne des Zscoresde ces 4 indicateurs, puis analysé les corrélations entre ZOSM, efficacités protéiques tissulaires (protéines tissulaires /protéines ingérées) et δ15N tissulaires.Résultats et Analyse statistique : La classification a distingué 3 groupes de rats : résistants à l'O et au SM (R, n=12),sensibles à l'O mais résistants au SM (O, n=12), ou sensibles à l'O et au SM (OSM, n=12). Les rats R, O et SM avaientles caractéristiques suivantes (moyennes ± écart-types, significativement différentes si elles portent des lettresdifférentes) : poids de 542 ± 42a, 620 ± 44b et 670 ± 33c g ; adiposité viscérale de 6,9 ± 0,5a, 8,3 ± 0,3b et 8,6 ± 0,7b % ;HOMA-IR de 7,1 ± 3,4a, 10,0 ± 5,7a et 21,7 ± 7,3b μg·mmol·L-2 ; triglycérides hépatiques de 57 ± 14a, 62 ± 20a et 101 ± 13b μmol·g-1 ; efficacités protéiques de 2,37 ± 0,20a, 2,41 ± 0,31ab et 2,62 ± 0,18b % dans le foie, 0,53 ± 0,08a, 0,49 ± 0,04aet 0,43 ± 0,04b % dans le muscle gastrocnémien, et 0,19 ± 0,02a, 0,17 ± 0,02ab et 0,16 ± 0,02b % dans le muscle tibialis.Le ZOSM était corrélé (P<0,01) positivement à l'efficacité protéique du foie (R=0,54) et négativement à celles des musclesgastrocnémien (R=-0,48) et tibialis (R=-0,45), et négativement au δ15N des protéines du foie (R=-0,47), érythrocytes (R=-0,43) et poils (R=-0,49).Conclusion : Dans ce modèle, la sensibilité à l'O et au SM concerne 2/3 de la population, avec 1/3 en O saine et 1/3 enO avec SM. Chez les individus sensibles, l'efficacité d'utilisation anabolique des protéines alimentaires est plus grandedans le foie mais plus faible dans certains muscles, et la plus grande efficacité anabolique hépatique est liée à unemoindre orientation catabolique des acides aminés dont attestent les plus faibles δ15N du foie et d'autres pools plusaccessibles (érythrocytes, poils).Conflits d’intérêts: Aucun conflit à déclare

Regulation of arginine metabolism by dietary fatty acids Involvement of PPARa

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Multi-omics phenotyping highlights organ-specific metabolic and inflammatory shifts associated with differential plant and animal protein intake in high fat fed rats

International audienc

Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error.

Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers

Evidence for a new structure in the J/ψpJ/\psi p and J/ψpˉJ/\psi \bar{p} systems in Bs0→J/ψppˉB_s^0 \to J/\psi p \bar{p} decays

International audienceAn amplitude analysis of flavor-untagged Bs0→J/ψpp¯ decays is performed using a sample of 797±31 decays reconstructed with the LHCb detector. The data, collected in proton-proton collisions between 2011 and 2018, correspond to an integrated luminosity of 9  fb-1. Evidence for a new structure in the J/ψp and J/ψp¯ systems with a mass of 4337-4+7 -2+2  MeV and a width of 29-12+26 -14+14  MeV is found, where the first uncertainty is statistical and the second systematic, with a significance in the range of 3.1 to 3.7σ, depending on the assigned JP hypothesis

Observation of Two New Excited Ξb0\Xi_b^0 States Decaying to Λb0K−π+\Lambda^0_b K^- \pi^+

International audienceTwo narrow resonant states are observed in the Λb0K-π+ mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment and corresponding to an integrated luminosity of 6  fb-1. The minimal quark content of the Λb0K-π+ system indicates that these are excited Ξb0 baryons. The masses of the Ξb(6327)0 and Ξb(6333)0 states are m[Ξb(6327)0]=6327.28-0.21+0.23±0.12±0.24 and m[Ξb(6333)0]=6332.69-0.18+0.17±0.03±0.22  MeV, respectively, with a mass splitting of Δm=5.41-0.27+0.26±0.12  MeV, where the uncertainties are statistical, systematic, and due to the Λb0 mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of Γ[Ξb(6327)0]&lt;2.20(2.56) and Γ[Ξb(6333)0]&lt;1.60(1.92)  MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Ξb0 resonances

Measurement of χc1_{c1}(3872) production in proton-proton collisions at s \sqrt{s} = 8 and 13 TeV

International audienceThe production cross-section of the χ$_{c1}$(3872) state relative to the ψ(2S) meson is measured using proton-proton collision data collected with the LHCb experiment at centre-of-mass energies of $\sqrt{s}$ = 8 and 13 TeV, corresponding to integrated luminosities of 2.0 and 5.4 fb$^{−1}$, respectively. The two mesons are reconstructed in the J/ψπ$^{+}$π$^{−}$ final state. The ratios of the prompt and nonprompt χ$_{c1}$(3872) to ψ(2S) production cross-sections are measured as a function of transverse momentum, p$_{T}$, and rapidity, y, of the χ$_{c1}$(3872) and ψ(2S) states, in the kinematic range 4 < p$_{T}$< 20 GeV/c and 2.0 < y < 4.5. The prompt ratio is found to increase with p$_{T}$, independently of y. For the prompt component, the double ratio of the χ$_{c1}$(3872) and ψ(2S) production cross-sections between 13 and 8 TeV is observed to be consistent with unity, independent of p$_{T}$ and centre-of-mass energy.[graphic not available: see fulltext