Dogs used as a large animal model of obesity-related insulin resistance

As for ethical and other reasons, studies of the pathophysiological mechanisms of obesity and its association with insulin resistance (IR) cannot be performed in man, researchers have to use appropriate animal models. Although dogs fed on a high-fat diet seem to meet the requirements to study this human syndrome, the canine model has hardly been used. Our objective was to study the lipoprotein metabolism and reverse cholesterol transport in healthy dogs, then in dogs with insulin resistance. We also aimed to describe the plasmatic changes associated with insulin resistance, and quantify the expression of genes involved in this disorder, in insulin target tissues (visceral adipose tissue and skeletal muscle). In healthy dogs, apoB100 exclusively appears in VLDL, whose high production is associated with a high fractional catabolism (5-fold greater than that of human). LDL-apoB100 metabolism is similar in dogs and humans. Our results showed that the healthy dog does not exhibit any CETP activity in vivo, and that reverse cholesterol transport is very active, with substantial selective uptake of HDL esterified cholesterol. Consequently, among species with no CETP activity, dogs provide an adequate model to study changes in this selective cholesterol uptake. The anomalies observed in lipoprotein profiles produced by FPLC in IR obese dogs were identical to those seen in IR man. Insulin resistance is associated with a decreased production of LDL apo B100, due to a reduced production, despite the increased catabolism. Both transcription and plasmatic results confirmed those found in man (overexpression of leptin mRNA, underexpression of adiponectin, GLUT4, LPL, PPAR and UCP mRNAs). Therefore, dogs could provide a useful research model, particularly to elucidate the molecular mechanisms involved in the development of insulin resistance and dyslipidemia.Pour des raisons notamment éthiques, il n'est pas possible d'étudier chez l'homme les phénomènes physiopathologiques associés à l'évolution conjointe de l'obésité et de la baisse de sensibilité à l'insuline. L'établissement de modèles animaux reflétant la pathologie humaine paraît donc indispensable. Le chien soumis à un régime hyperlipidique semblait répondre aux critères de sélection d'un modèle adapté à l'étude de ce syndrome. Il n'avait cependant été que peu exploré. Le but de notre travail a été d'une part, d'étudier le métabolisme des lipoprotéines et le transport inverse du cholestérol chez le chien sain, puis chez le chien insulinorésistant (IR) et d'autre part, de caractériser l'évolution des modifications plasmatiques associées à l'insulinorésistance, puis de quantifier, au sein de certains tissus cibles de l'insuline (tissus adipeux viscéral et musculaire), l'expression de gènes impliqués dans ce désordre métabolique. Chez le chien sain, l'apo B100 (apolipoprotéine B100) apparaît exclusivement dans les VLDL dont la production élevée est associée à un catabolisme important, égal à 5 fois celui de l'homme. Ces lipoprotéines subissent une lipolyse partielle, formant les LDL qui contiennent donc aussi de l'apoB100. L'apoB100 des LDL a un métabolisme similaire à celui de l'homme. Le chien sain ne manifeste pas d'activité CETP (cholesterol ester tranfer protein) in vivo, mais présente un transport inverse du cholestérol très actif, notamment associé à une importante capture sélective du cholestérol estérifié des HDL. Le chien pourrait donc s'avérer le meilleur modèle pour l'étude de la modulation de cette voie de retour du cholestérol. Les profils lipidiques des lipoprotéines, obtenus par chromatographie FPLC chez le chien obèse IR, ont montré les mêmes perturbations que chez l'homme IR. La production d'apo B100 dans les VLDL est augmentée et la lipolyse diminuée. La concentration en apo B100 des LDL est diminuée, conséquence d'une production réduite et d'un catabolisme augmenté. Les résultats obtenus aux niveaux transcriptionnel et plasmatique sont également conformes aux observations effectuées chez l'homme (surexpression du gène de la leptine, sous-expression de celui de l'adiponectine, du GLUT4, de la lipoprotéine lipase, des PPAR et des UCP notamment). Sur les deux plans de l'étude, nos résultats confirment que le chien pourrait constituer un bon modèle d'étude, notamment pour l'élucidation des mécanismes moléculaires impliqués dans le développement de l'insulinorésistance et des dyslipidémies

Study of the p−-p−-K+^+ and p−-p−-K−^- dynamics using the femtoscopy technique

International audienceThe interactions of kaons (K) and antikaons ($\mathrm{\overline{K}}$) with few nucleons (N) were studied so far using kaonic atom data and measurements of kaon production and interaction yields in nuclei. Some details of the three-body KNN and $\mathrm{\overline{K}}$NN dynamics are still not well understood, mainly due to the overlap with multi-nucleon interactions in nuclei. An alternative method to probe the dynamics of three-body systems with kaons is to study the final state interaction within triplet of particles emitted in pp collisions at the Large Hadron Collider, which are free from effects due to the presence of bound nucleons. This Letter reports the first femtoscopic study of p$-$p$-$K$^+$ and p$-$p$-$K$^-$ correlations measured in high-multiplicity pp collisions at $\sqrt{s}$ = 13 TeV by the ALICE Collaboration. The analysis shows that the measured p$-$p$-$K$^+$ and p$-$p$-$K$^-$ correlation functions can be interpreted in terms of pairwise interactions in the triplets, indicating that the dynamics of such systems is dominated by the two-body interactions without significant contributions from three-body effects or bound states

Studying strangeness and baryon production mechanisms through angular correlations between charged Ξ\Xi baryons and identified hadrons in pp collisions at s\sqrt{s} = 13 TeV

International audienceThe angular correlations between charged $\Xi$ baryons and associated identified hadrons (pions, kaons, protons, $\Lambda$ baryons, and $\Xi$ baryons) are measured in pp collisions at $\sqrt{s} = 13$ TeV with the ALICE detector to give insight into the particle production mechanisms and balancing of quantum numbers on the microscopic level. In particular, the distribution of strangeness is investigated in the correlations between the doubly-strange $\Xi$ baryon and mesons and baryons that contain a single strange quark, K and $\Lambda$. As a reference, the results are compared to $\Xi\pi$ and $\Xi\mathrm{p}$ correlations, where the associated mesons and baryons do not contain a strange valence quark. These measurements are expected to be sensitive to whether strangeness is produced through string breaking or in a thermal production scenario. Furthermore, the multiplicity dependence of the correlation functions is measured to look for the turn-on of additional particle production mechanisms with event activity. The results are compared to predictions from the string-breaking model PYTHIA 8, including tunes with baryon junctions and rope hadronisation enabled, the cluster hadronisation model HERWIG 7, and the core-corona model EPOS-LHC. While some aspects of the experimental data are described quantitatively or qualitatively by the Monte Carlo models, no one model can match all features of the data. These results provide stringent constraints on the strangeness and baryon number production mechanisms in pp collisions

Observation of medium-induced yield enhancement and acoplanarity broadening of low-pTp_\mathrm{T} jets from measurements in pp and central Pb−-Pb collisions at sNN=5.02\sqrt{s_{\rm NN}}=5.02 TeV

International audienceThe ALICE Collaboration reports the measurement of semi-inclusive distributions of charged-particle jets recoiling from a high transverse momentum (high $p_{\rm T}$) hadron trigger in proton$-$proton and central Pb$-$Pb collisions at $\sqrt{s_{\rm NN}} = 5.02$ TeV. A data-driven statistical method is used to mitigate the large uncorrelated background in central Pb$-$Pb collisions. Recoil jet distributions are reported for jet resolution parameter $R=0.2$, 0.4, and 0.5 in the range $7 < p_{\rm T,jet} < 140$ GeV$/c$ and trigger$-$recoil jet azimuthal separation $\pi/2 < \Delta\varphi < \pi$. The measurements exhibit a marked medium-induced jet yield enhancement at low $p_{\rm T}$ and at large azimuthal deviation from $\Delta\varphi\sim\pi$. The enhancement is characterized by its dependence on $\Delta\varphi$, which has a slope that differs from zero by 4.7$\sigma$. Comparisons to model calculations incorporating different formulations of jet quenching are reported. These comparisons indicate that the observed yield enhancement arises from the response of the QGP medium to jet propagation

Skewness and kurtosis of mean transverse momentum fluctuations at the LHC energies

International audienceThe first measurements of skewness and kurtosis of mean transverse momentum ($\langle p_\mathrm{T}\rangle$) fluctuations are reported in Pb$-$Pb collisions at $\sqrt{s_\mathrm{NN}}$ = 5.02 TeV, Xe$-$Xe collisions at $\sqrt{s_\mathrm{NN}}$$=$ 5.44 TeV and pp collisions at $\sqrt{s} = 5.02$ TeV using the ALICE detector. The measurements are carried out as a function of system size $\langle \mathrm{d}N_\mathrm{ch}/\mathrm{d}\eta\rangle_{|\eta|<0.5}^{1/3}$, using charged particles with transverse momentum ($p_\mathrm{T}$) and pseudorapidity ($\eta$), in the range $0.2 < p_\mathrm{T} < 3.0$ GeV/$c$ and $|\eta| < 0.8$, respectively. In Pb$-$Pb and Xe$-$Xe collisions, positive skewness is observed in the fluctuations of $\langle p_\mathrm{T}\rangle$ for all centralities, which is significantly larger than what would be expected in the scenario of independent particle emission. This positive skewness is considered a crucial consequence of the hydrodynamic evolution of the hot and dense nuclear matter created in heavy-ion collisions. Furthermore, similar observations of positive skewness for minimum bias pp collisions are also reported here. Kurtosis of $\langle p_\mathrm{T}\rangle$ fluctuations is found to be in good agreement with the kurtosis of Gaussian distribution, for most central Pb$-$Pb collisions. Hydrodynamic model calculations with MUSIC using Monte Carlo Glauber initial conditions are able to explain the measurements of both skewness and kurtosis qualitatively from semicentral to central collisions in Pb--Pb system. Color reconnection mechanism in PYTHIA8 model seems to play a pivotal role in capturing the qualitative behavior of the same measurements in pp collisions

Light-flavor particle production in high-multiplicity pp collisions at s=13\mathbf{\sqrt{\textit{s}} = 13} TeV as a function of transverse spherocity

International audienceResults on the transverse spherocity dependence of light-flavor particle production ($\pi$, K, p, $\phi$, ${\rm K^{*0}}$, ${\rm K}^{0}_{\rm{S}}$, $\Lambda$, $\Xi$) at midrapidity in high-multiplicity pp collisions at $\sqrt{s} = 13$ TeV were obtained with the ALICE apparatus. The transverse spherocity estimator ($S_{{\rm O}}^{{\it p}_{\rm T}=1}$) categorizes events by their azimuthal topology. Utilizing narrow selections on $S_{\text{O}}^{{\it p}_{\rm T}=1}$, it is possible to contrast particle production in collisions dominated by many soft initial interactions with that observed in collisions dominated by one or more hard scatterings. Results are reported for two multiplicity estimators covering different pseudorapidity regions. The $S_{{\rm O}}^{{\it p}_{\rm T}=1}$ estimator is found to effectively constrain the hardness of the events when the midrapidity ($\left | \eta \right |< 0.8$) estimator is used. The production rates of strange particles are found to be slightly higher for soft isotropic topologies, and severely suppressed in hard jet-like topologies. These effects are more pronounced for hadrons with larger mass and strangeness content, and observed when the topological selection is done within a narrow multiplicity interval. This demonstrates that an important aspect of the universal scaling of strangeness enhancement with final-state multiplicity is that high-multiplicity collisions are dominated by soft, isotropic processes. On the contrary, strangeness production in events with jet-like processes is significantly reduced. The results presented in this article are compared with several QCD-inspired Monte Carlo event generators. Models that incorporate a two-component phenomenology, either through mechanisms accounting for string density, or thermal production, are able to describe the observed strangeness enhancement as a function of $S_{{\rm O}}^{{\it p}_{\rm T}=1}$

Measurement of the low-energy antitriton inelastic cross section

International audienceIn this Letter, the first measurement of the inelastic cross section for antitriton$-$nucleus interactions is reported, covering the momentum range of $0.8 \leq p < 2.4$ GeV/$c$. The measurement is carried out using data recorded with the ALICE detector in pp and Pb$-$Pb collisions at a centre-of-mass energy per nucleon of 13 TeV and 5.02 TeV, respectively. The detector material serves as an absorber for antitriton nuclei. The raw yield of (anti)triton nuclei measured with the ALICE apparatus is compared to the results from detailed ALICE simulations based on the GEANT4 toolkit for the propagation of (anti)particles through matter, allowing one to quantify the inelastic interaction probability in the detector material. This analysis complements the measurement of the inelastic cross section of antinuclei up to $A=3$ carried out by the ALICE Collaboration, and demonstrates the feasibility of the study of the isospin dependence of inelastic interaction cross section with the analysis techniques presented in this Letter

Measurements of jet quenching using semi-inclusive hadron+jet distributions in pp and central Pb−-Pb collisions at sNN=5.02\sqrt{s_{\rm NN}}=5.02 TeV

International audienceThe ALICE Collaboration reports measurements of the semi-inclusive distribution of charged-particle jets recoiling from a high transverse momentum (high $p_{\rm T}$) charged hadron, in pp and central Pb$-$Pb collisions at center of mass energy per nucleon$-$nucleon collision $\sqrt{s_{\rm NN}}=5.02$ TeV. The large uncorrelated background in central Pb$-$Pb collisions is corrected using a data-driven statistical approach, which enables precise measurement of recoil jet distributions over a broad range in $p_{\rm T,ch\,jet}$ and jet resolution parameter $R$. Recoil jet yields are reported for $R=0.2$, 0.4, and 0.5 in the range $7 < p_{\rm T,ch\, jet} < 140$ GeV$/c$ and $\pi/2<\Delta\varphi<\pi$, where $\Delta\varphi$ is the azimuthal angular separation between hadron trigger and recoil jet. The low $p_{\rm T,ch\,jet}$ reach of the measurement explores unique phase space for studying jet quenching, the interaction of jets with the quark-gluonnplasma generated in high-energy nuclear collisions. Comparison of $p_{\rm T,ch\,jet}$ distributions from pp and central Pb$-$Pb collisions probes medium-induced jet energy loss and intra-jet broadening, while comparison of their acoplanarity distributions explores in-medium jet scattering and medium response. The measurements are compared to theoretical calculations incorporating jet quenching

Study of the p−-p−-K+^+ and p−-p−-K−^- dynamics using the femtoscopy technique

The interactions of kaons (K) and antikaons ($\mathrm{\overline{K}}$) with few nucleons (N) were studied so far using kaonic atom data and measurements of kaon production and interaction yields in nuclei. Some details of the three-body KNN and $\mathrm{\overline{K}}$NN dynamics are still not well understood, mainly due to the overlap with multi-nucleon interactions in nuclei. An alternative method to probe the dynamics of three-body systems with kaons is to study the final state interaction within triplet of particles emitted in pp collisions at the Large Hadron Collider, which are free from effects due to the presence of bound nucleons. This Letter reports the first femtoscopic study of p$-$p$-$K$^+$ and p$-$p$-$K$^-$ correlations measured in high-multiplicity pp collisions at $\sqrt{s} = 13$ TeV by the ALICE Collaboration. The analysis shows that the measured p$-$p$-$K$^+$ and p$-$p$-$K$^-$ correlation functions can be interpreted in terms of pairwise interactions in the triplets, indicating that the dynamics of such systems is dominated by the two-body interactions without significant contributions from three-body effects or bound states.The interactions of kaons (K) and antikaons ($\mathrm{\overline{K}}$) with few nucleons (N) were studied so far using kaonic atom data and measurements of kaon production and interaction yields in nuclei. Some details of the three-body KNN and $\mathrm{\overline{K}}$NN dynamics are still not well understood, mainly due to the overlap with multi-nucleon interactions in nuclei. An alternative method to probe the dynamics of three-body systems with kaons is to study the final state interaction within triplet of particles emitted in pp collisions at the Large Hadron Collider, which are free from effects due to the presence of bound nucleons. This Letter reports the first femtoscopic study of p$-$p$-$K$^+$ and p$-$p$-$K$^-$ correlations measured in high-multiplicity pp collisions at $\sqrt{s}$ = 13 TeV by the ALICE Collaboration. The analysis shows that the measured p$-$p$-$K$^+$ and p$-$p$-$K$^-$ correlation functions can be interpreted in terms of pairwise interactions in the triplets, indicating that the dynamics of such systems is dominated by the two-body interactions without significant contributions from three-body effects or bound states