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1. Major depletion of insulin sensitivity-associated taxa in the gut microbiome of persons living with HIV controlled by antiretroviral drugs

Author

Belda, Eugeni, Capeau, Jacqueline, Zucker, Jean-Daniel, Chatelier, Emmanuelle Le, Pons, Nicolas, Oñate, Florian Plaza, Quinquis, Benoit, Alili, Rohia, Fellahi, Soraya, Katlama, Christine, Clément, Karine, Fève, Bruno, Jaureguiberry, Stéphane, Goujard, Cécile, Lambotte, Olivier, Doré, Joël, Prifti, Edi, and Bastard, Jean-Philippe

Published
2024
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3. Protein supplementation changes gut microbial diversity and derived metabolites in subjects with type 2 diabetes

Author

Attaye, Ilias, Lassen, Pierre Bel, Adriouch, Solia, Steinbach, Emilie, Patiño-Navarrete, Rafael, Davids, Mark, Alili, Rohia, Jacques, Flavien, Benzeguir, Sara, Belda, Eugeni, Nemet, Ina, Anderson, James T., Alexandre-Heymann, Laure, Greyling, Arno, Larger, Etienne, Hazen, Stanley L., van Oppenraaij, Sophie L., Tremaroli, Valentina, Beck, Katharina, Bergh, Per-Olof, Bäckhed, Fredrik, ten Brincke, Suzan P.M., Herrema, Hilde, Groen, Albert K., Pinto-Sietsma, Sara-Joan, Clément, Karine, and Nieuwdorp, Max

Published
2023
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4. Unraveling the role of the upper small intestine microbiome in metabolic diseases: insight on new potential therapeutic interventions

Author

Belda, Eugeni, primary, Steinbach, Emilie, additional, Alili, Rohia, additional, Adriouch, Solia, additional, Masi, Davide, additional, Colas, Emavieve, additional, Dauriat, Charlene, additional, Donatelli, Gianfranco, additional, Doumont, Jean-Loup, additional, Genser, Laurent, additional, Jacques, Flavien, additional, Kordahi, Melissa, additional, Pelloux, Veronique, additional, Sokol, Harry, additional, Taillandier, Paul, additional, Tuszunski, Thierry, additional, Chassaing, Benoit, additional, Le, Roy Tiphaine, additional, and Clement, Karine, additional

Published
2024
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5. Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

Author

Andrikopoulos, Petros, Aron-Wisnewsky, Judith, Chakaroun, Rima, Myridakis, Antonis, Forslund, Sofia K., Nielsen, Trine, Adriouch, Solia, Holmes, Bridget, Chilloux, Julien, Vieira-Silva, Sara, Falony, Gwen, Salem, Joe Elie, Andreelli, Fabrizio, Belda, Eugeni, Kieswich, Julius, Chechi, Kanta, Puig-Castellvi, Francesc, Chevalier, Mickael, Le Chatelier, Emmanuelle, Olanipekun, Michael T., Hoyles, Lesley, Alves, Renato, Helft, Gerard, Isnard, Richard, Køber, Lars, Coelho, Luis Pedro, Rouault, Christine, Gauguier, Dominique, Gøtze, Jens Peter, Prifti, Edi, Froguel, Philippe, Alili, Rohia, Galijatovic, Ehm Astrid Andersson, Barthelemy, Olivier, Bastard, Jean Philippe, Batisse, Jean Paul, Bel-Lassen, Pierre, Berland, Magalie, Bittar, Randa, Blottière, Hervé, Bosquet, Frederic, Boubrit, Rachid, Bourron, Olivier, Camus, Mickael, Ciangura, Cecile, Collet, Jean Philippe, Dietrich, Arne, Djebbar, Morad, Doré, Angélique, Engelbrechtsen, Line, Fezeu, Leopold, Fromentin, Sebastien, Pons, Nicolas, Graine, Marianne, Grünemann, Caroline, Hartemann, Agnes, Hartmann, Bolette, Hornbak, Malene, Jaqueminet, Sophie, Jørgensen, Niklas Rye, Julienne, Hanna, Justesen, Johanne, Kammer, Judith, Karup, Nikolaj, Kozlowski, Ruby, Kuhn, Michael, Lejard, Véronique, Letunic, Ivica, Levenez, Florence, Marko, Lajos, Martinez-Gili, Laura, Massey, Robin, Maziers, Nicolas, Moitinho-Silva, Lucas, Montalescot, Gilles, Neves, Ana Luisa, Le Pavin, Laetitia Pasero, Pousset, Francoise, Rodriguez-Martinez, Andrea, Schmidt, Sebastien, Schütz, Tatjana, Silva, Lucas, Silvain, Johanne, Svendstrup, Mathilde, Swartz, Timothy D., Vanduyvenboden, Thierry, Verger, Eric O., Walther, Stefanie, Zucker, Jean Daniel, Bäckhed, Fredrik, Vestergaard, Henrik, Hansen, Torben, Oppert, Jean Michel, Blüher, Matthias, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Yaqoob, Muhammad M., Stumvoll, Michael, Pedersen, Oluf, Ehrlich, S. Dusko, Clément, Karine, Dumas, Marc Emmanuel, Andrikopoulos, Petros, Aron-Wisnewsky, Judith, Chakaroun, Rima, Myridakis, Antonis, Forslund, Sofia K., Nielsen, Trine, Adriouch, Solia, Holmes, Bridget, Chilloux, Julien, Vieira-Silva, Sara, Falony, Gwen, Salem, Joe Elie, Andreelli, Fabrizio, Belda, Eugeni, Kieswich, Julius, Chechi, Kanta, Puig-Castellvi, Francesc, Chevalier, Mickael, Le Chatelier, Emmanuelle, Olanipekun, Michael T., Hoyles, Lesley, Alves, Renato, Helft, Gerard, Isnard, Richard, Køber, Lars, Coelho, Luis Pedro, Rouault, Christine, Gauguier, Dominique, Gøtze, Jens Peter, Prifti, Edi, Froguel, Philippe, Alili, Rohia, Galijatovic, Ehm Astrid Andersson, Barthelemy, Olivier, Bastard, Jean Philippe, Batisse, Jean Paul, Bel-Lassen, Pierre, Berland, Magalie, Bittar, Randa, Blottière, Hervé, Bosquet, Frederic, Boubrit, Rachid, Bourron, Olivier, Camus, Mickael, Ciangura, Cecile, Collet, Jean Philippe, Dietrich, Arne, Djebbar, Morad, Doré, Angélique, Engelbrechtsen, Line, Fezeu, Leopold, Fromentin, Sebastien, Pons, Nicolas, Graine, Marianne, Grünemann, Caroline, Hartemann, Agnes, Hartmann, Bolette, Hornbak, Malene, Jaqueminet, Sophie, Jørgensen, Niklas Rye, Julienne, Hanna, Justesen, Johanne, Kammer, Judith, Karup, Nikolaj, Kozlowski, Ruby, Kuhn, Michael, Lejard, Véronique, Letunic, Ivica, Levenez, Florence, Marko, Lajos, Martinez-Gili, Laura, Massey, Robin, Maziers, Nicolas, Moitinho-Silva, Lucas, Montalescot, Gilles, Neves, Ana Luisa, Le Pavin, Laetitia Pasero, Pousset, Francoise, Rodriguez-Martinez, Andrea, Schmidt, Sebastien, Schütz, Tatjana, Silva, Lucas, Silvain, Johanne, Svendstrup, Mathilde, Swartz, Timothy D., Vanduyvenboden, Thierry, Verger, Eric O., Walther, Stefanie, Zucker, Jean Daniel, Bäckhed, Fredrik, Vestergaard, Henrik, Hansen, Torben, Oppert, Jean Michel, Blüher, Matthias, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Yaqoob, Muhammad M., Stumvoll, Michael, Pedersen, Oluf, Ehrlich, S. Dusko, Clément, Karine, and Dumas, Marc Emmanuel

Abstract

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied “explainable” machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.

Published
2023

6. The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass

Author

Debédat, Jean, primary, Le Roy, Tiphaine, additional, Voland, Lise, additional, Belda, Eugeni, additional, Alili, Rohia, additional, Adriouch, Solia, additional, Bel Lassen, Pierre, additional, Kasahara, Kazuyuki, additional, Hutchison, Evan, additional, Genser, Laurent, additional, Torres, Licia, additional, Gamblin, Camille, additional, Rouault, Christine, additional, Zucker, Jean-Daniel, additional, Kapel, Nathalie, additional, Poitou, Christine, additional, Marcelin, Geneviève, additional, Rey, Federico E., additional, Aron-Wisnewsky, Judith, additional, and Clément, Karine, additional

Published
2022
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8. Microbiote intestinal et obésité : Intérêt du séquençage par nanopore dans la détection des signatures métagénomiques dans l'obésité et lors d'interventions nutritionnelles

Author

Alili, Rohia and STAR, ABES

Subjects
Bariatric surgery, Microbiote intestinal, Gut microbiota, Obesité, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Chirurgie bariatrique, Nanopore Sequencing, Dietary intervention, Intervention diététique, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Signatures métagénomiques, Séquençage Nanopore, Obesity, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Metagenomic signatures
Abstract

It is now accepted that the gut microbiota (GM) plays a role in the physiopathology of obesity. Several recent studies have shown it is possible to stratify subjects with obesity and overweight according to the gene richness and the diversity of their GM. An association has been demonstrated between the GM composition and the clinical and biological phenotype of obese subjects as well as with responses to interventions aimed weight loss. Recently, within the European MetaCardis consortium, our team revealed a particular profile of the microbiota, the enterotype Bacteroides2 (bact2), enriched in severely obese subjects and associated with metabolic and inflammatory deterioration.It is therefore interesting to develop methods for rapid sequencing of subjects' GM in order to stratify them and to test the hypothesis that the basal state of the GM could be predictive of the response to dietary or surgical interventions. In line with these objectives, we have developed a process that comprises collecting stools from patients with overweight or obese to the generation of metagenomic sequencing data with the MinION tool from Oxford Nanopore Technologies (ONT) within our medical department and laboratory. We then examined the GM of two cohorts: a bariatric surgery (BS) cohort and the other from a real-life calorie restriction intervention with probiotic supplementation, with a focus on the Bact2 enterotype, which has previously been associated with more deteriorated metabolic health.We were able to verify the satisfactory results obtained by Nanopore sequencing and also detect certain limitations of this technology. Our work in a cohort of 263 overweight and obese subjects allowed us to demonstrate the capacity of our technological approach to stratify subjects according to the composition of their GM. For example, Bact2 was predominant in subjects with obesity and more severe metabolic alterations. After 10% weight loss in the dietary intervention study (163 matched subjects), and in parallel with the metabolic improvements observed, a decrease in the prevalence of Bact2 was observed as well as a decrease in certain pro-inflammatory bacteria. This approach has been repeated in severely obese patients who are candidates for bariatric surgery.In conclusion, we have implemented a rapid assessment method for dysbiosis in obesity that allows us to detect Bact2 which could be a potential predictor of anthropometric and metabolic responses to weight loss interventions. Indeed, the prediction of responses to dietary and BS interventions could be an important tool in clinical practice by improving the selection of patients for whom a different or more targeted management could be considered., Il est maintenant admis que le microbiote intestinal (MI) joue un rôle dans la physiopathologie de l'obésité. Plusieurs études menées récemment ont permis de stratifier les sujets obèses et en surpoids, en fonction de la richesse génétique et de la diversité de leur MI. Une association a été démontrée entre de la composition du MI et le phénotype clinique et biologique des sujets en situation d'obésité ainsi qu'avec les réponses aux interventions visant une perte de poids. Récemment, notre équipe avec le consortium européen MétaCardis a mis en évidence un profil particulier du microbiote, l'entérotype Bacteroides2 (bact2), enrichis chez des sujets sévèrement obèses et associé à une détérioration métabolique et inflammatoire.Il est donc intéressant de développer des méthodes de séquençage rapide du MI des sujets afin de pouvoir les stratifier et de tester l'hypothèse que l'état basal du MI pourrait être prédicteur de la réponse aux interventions diététiques ou chirurgicales. En lien avec ces objectifs, nous avons développé au sein du laboratoire et du service clinique un processus allant du recueil des selles de patients en situation de surpoids ou d'obésité jusqu'à la génération de données métagénomiques de séquençage avec l'outil MinION d'Oxford Nanopore Technologies (ONT). Nous avons par la suite, examiné le microbiote de deux cohortes, une bariatrique et l'autre d'une intervention de restriction calorique en vie réelle avec supplémentation en probiotiques, avec un focus sur l'entérotype Bact2 qui a été précédemment associé à une santé métabolique plus détériorée.Nous avons pu vérifier les résultats satisfaisants obtenus par séquençage Nanopore et également détecter certaines limites de cette technologie. Nos travaux dans une cohorte de 263 sujets en surpoids et obèses nous ont permis de démontrer la capacité de notre approche technologique à stratifier les sujets en fonction de la composition de leur MI. Par exemple, Bact2 était prédominant chez les sujets avec une obésité et des altérations métaboliques plus sévères. Après une perte de 10% du poids initial dans l'étude d‘intervention diététique (163 sujets appariés) et, en parallèle des améliorations métaboliques constatées, une diminution de la prévalence de Bact2 a été observée ainsi qu'une diminution de certaines bactéries pro-inflammatoires. Cette approche a été répétée chez des patients sévèrement obèses candidats à la chirurgie bariatrique (CB).En conclusion, nous avons mis en place une méthode d'évaluation rapide de la dysbiose dans l'obésité qui nous permet de détecter Bact2 qui pourrait être un prédicteur potentiel des réponses anthropométrique et métabolique aux interventions de perte de poids. En effet, la prédiction des réponses aux interventions diététiques et de CB pourrait être un outil important dans la pratique clinique, en améliorant la sélection des patients pour lesquels une prise en charge différente ou plus ciblée pourrait être envisagée.

Published
2022

9. Characterization of the Gut Microbiota in Individuals with Overweight or Obesity during a Real-World Weight Loss Dietary Program: A Focus on the Bacteroides 2 Enterotype

Author

Alili, Rohia, primary, Belda, Eugeni, additional, Fabre, Odile, additional, Pelloux, Véronique, additional, Giordano, Nils, additional, Legrand, Rémy, additional, Bel Lassen, Pierre, additional, Swartz, Timothy D., additional, Zucker, Jean-Daniel, additional, and Clément, Karine, additional

Published
2021
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13. Adipocyte ATP-Binding Cassette G1 Promotes Triglyceride Storage, Fat Mass Growth, and Human Obesity

Author

Frisdal, Eric, Le Lay, Soazig, Hooton, Henri, Poupel, Lucie, Olivier, Maryline, Alili, Rohia, Plengpanich, Wanee, Villard, Elise F., Gilibert, Sophie, Lhomme, Marie, Superville, Alexandre, Miftah-Alkhair, Lobna, Chapman, M. John, Dallinga-Thie, Geesje M., Venteclef, Nicolas, Poitou, Christine, Tordjman, Joan, Lesnik, Philippe, Kontush, Anatol, Huby, Thierry, Dugail, Isabelle, Clement, Karine, Guerin, Maryse, and Le Goff, Wilfried

Published
2015
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14. Comprehensive Wet-Bench and Bioinformatics Workflow for Complex Microbiota Using Oxford Nanopore Technologies

Author

Ammer-Herrmenau, Christoph, primary, Pfisterer, Nina, additional, van den Berg, Tim, additional, Gavrilova, Ivana, additional, Amanzada, Ahmad, additional, Singh, Shiv K., additional, Khalil, Alaa, additional, Alili, Rohia, additional, Belda, Eugeni, additional, Clement, Karine, additional, Abd El Wahed, Ahmed, additional, Gady, ElSagad Eltayeb, additional, Haubrock, Martin, additional, Beißbarth, Tim, additional, Ellenrieder, Volker, additional, and Neesse, Albrecht, additional

Published
2021
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16. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Author

Couto Alves, Alexessander, De Silva, N Maneka G, Karhunen, Ville, Sovio, Ulla, Das, Shikta, Taal, H Rob, Warrington, Nicole M, Lewin, Alexandra M, Kaakinen, Marika, Cousminer, Diana L, Thiering, Elisabeth, Timpson, Nicholas J, Bond, Tom A, Lowry, Estelle, Brown, Christopher D, Estivill, Xavier, Lindi, Virpi, Bradfield, Jonathan P, Geller, Frank, Speed, Doug, Coin, Lachlan J M, Loh, Marie, Barton, Sheila J, Beilin, Lawrence J, Bisgaard, Hans, Bønnelykke, Klaus, Alili, Rohia, Hatoum, Ida J, Schramm, Katharina, Cartwright, Rufus, Charles, Marie-Aline, Salerno, Vincenzo, Clément, Karine, Claringbould, Annique A J, Van Duijn, Cornelia M, Moltchanova, Elena, Eriksson, Johan G, Elks, Cathy, Feenstra, Bjarke, Flexeder, Claudia, Franks, Stephen, Frayling, Timothy M, Freathy, Rachel M, Elliott, Paul, Widén, Elisabeth, Hakonarson, Hakon, Hattersley, Andrew T, Rodriguez, Alina, Banterle, Marco, Heinrich, Joachim, Heude, Barbara, Holloway, John W, Hofman, Albert, Hyppönen, Elina, Inskip, Hazel, Kaplan, Lee M, Hedman, Asa K, Läärä, Esa, Prokisch, Holger, Grallert, Harald, Lakka, Timo A, Lawlor, Debbie A, Melbye, Mads, Ahluwalia, Tarunveer S, Marinelli, Marcella, Millwood, Iona Y, Palmer, Lyle J, Pennell, Craig E, Perry, John R, Ring, Susan M, Savolainen, Markku J, Rivadeneira, Fernando, Standl, Marie, Sunyer, Jordi, Tiesler, Carla M T, Uitterlinden, Andre G, Schierding, William, O'Sullivan, Justin M, Prokopenko, Inga, Herzig, Karl-Heinz, Smith, George Davey, O'Reilly, Paul, Felix, Janine F, Buxton, Jessica L, Blakemore, Alexandra I F, Ong, Ken K, Jaddoe, Vincent W V, Grant, Struan F A, Sebert, Sylvain, McCarthy, Mark I, Järvelin, Marjo-Riitta, Erasmus MC other, Epidemiology, Internal Medicine, Pediatrics, Medical Research Council (MRC), Sovio, Ulla [0000-0002-0799-1105], Perry, John [0000-0001-6483-3771], Ong, Kenneth [0000-0003-4689-7530], Apollo - University of Cambridge Repository, Warrington, Nicole M [0000-0003-4195-775X], Lewin, Alexandra M [0000-0003-0081-7582], Kaakinen, Marika [0000-0002-9228-0462], Cousminer, Diana L [0000-0001-8864-7893], Timpson, Nicholas J [0000-0002-7141-9189], Lowry, Estelle [0000-0002-4655-416X], Brown, Christopher D [0000-0002-3785-5008], Estivill, Xavier [0000-0002-0723-2256], Geller, Frank [0000-0002-9238-3269], Speed, Doug [0000-0002-0096-9765], Coin, Lachlan J M [0000-0002-4300-455X], Loh, Marie [0000-0003-3626-8466], Barton, Sheila J [0000-0003-4963-4242], Alili, Rohia [0000-0002-0158-4250], Schramm, Katharina [0000-0002-8809-3170], Charles, Marie-Aline [0000-0003-4025-4390], Claringbould, Annique A J [0000-0002-9201-6557], van Duijn, Cornelia M [0000-0002-2374-9204], Feenstra, Bjarke [0000-0003-1478-649X], Frayling, Timothy M [0000-0001-8362-2603], Freathy, Rachel M [0000-0003-4152-2238], Widén, Elisabeth [0000-0001-7108-2806], Hakonarson, Hakon [0000-0003-2814-7461], Rodriguez, Alina [0000-0003-1209-8802], Heude, Barbara [0000-0002-1565-1629], Holloway, John W [0000-0001-9998-0464], Hofman, Albert [0000-0002-9865-121X], Hyppönen, Elina [0000-0003-3670-9399], Inskip, Hazel [0000-0001-8897-1749], Kaplan, Lee M [0000-0002-6301-2696], Prokisch, Holger [0000-0003-2379-6286], Lakka, Timo A [0000-0002-9199-2871], Lawlor, Debbie A [0000-0002-6793-2262], Melbye, Mads [0000-0001-8264-6785], Ahluwalia, Tarunveer S [0000-0002-7464-3354], Marinelli, Marcella [0000-0002-5450-3960], Palmer, Lyle J [0000-0002-1628-3055], Pennell, Craig E [0000-0002-0937-6165], Perry, John R [0000-0001-6483-3771], Ring, Susan M [0000-0003-3103-9330], Savolainen, Markku J [0000-0002-2557-6423], Rivadeneira, Fernando [0000-0001-9435-9441], Sunyer, Jordi [0000-0002-2602-4110], Schierding, William [0000-0001-5659-2701], O'Sullivan, Justin M [0000-0003-2927-450X], Prokopenko, Inga [0000-0003-1624-7457], Smith, George Davey [0000-0002-1407-8314], Felix, Janine F [0000-0002-9801-5774], Ong, Ken K [0000-0003-4689-7530], Jaddoe, Vincent W V [0000-0003-2939-0041], Sebert, Sylvain [0000-0001-6681-6983], McCarthy, Mark I [0000-0002-4393-0510], and Järvelin, Marjo-Riitta [0000-0002-2149-0630]

Subjects
Adult, Male, Pharmacogenomic Variants, Quantitative Trait Loci, BLOOD-PRESSURE, 030209 endocrinology & metabolism, Polymorphism, Single Nucleotide, Body Mass Index, EARLY-LIFE, 03 medical and health sciences, AGE, Quantitative Trait, Heritable, 0302 clinical medicine, Humans, Genetic Predisposition to Disease, Longitudinal Studies, 030212 general & internal medicine, GENOME-WIDE ASSOCIATION, METABOLIC RISK, Growth Charts, FTO GENE, Child, Research Articles, Genetic Association Studies, Adaptor Proteins, Signal Transducing, 2. Zero hunger, Science & Technology, BIRTH COHORT, Intracellular Signaling Peptides and Proteins, nutritional and metabolic diseases, SciAdv r-articles, Infant, Human Genetics, Genomics, 3. Good health, Multidisciplinary Sciences, BODY-MASS INDEX, OBESITY, Science & Technology - Other Topics, Receptors, Leptin, ADIPOSITY, Female, biological, Research Article, Genome-Wide Association Study
Abstract

Longitudinal data find a new variant controlling BMI in infancy and reveal genetic differences between infant and adult BMI., Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

Published
2019

17. Altered subcutaneous adipose tissue parameters after switching ART-controlled HIV+ patients to raltegravir/maraviroc

Author

Bastard, Jean-Philippe, primary, Pelloux, Véronique, additional, Alili, Rohia, additional, Fellahi, Soraya, additional, Aron-Wisnewsky, Judith, additional, Capel, Emilie, additional, Fève, Bruno, additional, Assoumou, Lambert, additional, Prifti, Edi, additional, Katlama, Christine, additional, Clément, Karine, additional, and Capeau, Jacqueline, additional

Published
2021
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18. Microbiote intestinal et obésité : Identification d'une signature de la dysbiose chez le sujet obèse morbide par la technologie Oxford Nanopore

Author

Alili, Rohia, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), ALILI, Rohia, and Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN)

Subjects
[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Obésité – Dysbiose - Diversité bactérienne - Séquençage – Oxford Nanopore, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

L’Homme vit en symbiose avec une importante population microbienne qui colonise son tractus digestif et qui constitue son microbiote. La perturbation de ce mécanisme de symbiose induit une altération qualitative et fonctionnelle du microbiote intestinal provoquant ainsi une dysbiose qui pourrait expliquer certaines maladies auto-immunes ou inflammatoires telle que l’obésité.Chez l’Homme, plusieurs études ont été menées et ont démontrées que le microbiote intestinal pourrait relier les modifications des modes alimentaires aux altérations du métabolisme, du stockage énergétique et de l’inflammation chronique systémique et tissulaire caractérisant l’obésité. On a constaté par la suite, que pour une partie des sujets obèses, la diversité bactérienne était réduite, une diminution qui a été associée à des dysfonctionnements métaboliques plus marqués comparativement à des sujets obèses dont la diversité bactérienne est préservée. Au cours de la chirurgie, la dysbiose s’améliore mais n’est pas corrigée. Notre étude vise à caractériser par une nouvelle méthode (la technologie Nanopore), les anomalies du microbiote intestinal chez des patients à différents stade d’obésité et lors d’interventions visant à perdre du poids. Ce développement technologique permettrait dans le futur d’établir des moyens diagnostics de la dysbiose chez ces patients sévèrement obèses et plus généralement dans d’autres pathologies chroniques.Afin de pouvoir explorer le microbiote intestinal humain et pouvoir stratifier nos patients obèses en fonction de leur diversité bactérienne intestinale, j’ai développé au sein du laboratoire Nutriomique/Centre de Recherche en Nutrition Humaine Ile de France, une technologie de séquençage basée sur l’utilisation de l’outil MinION d’Oxford Nanopore. Pour cela j’ai mis au point un procédé de recueil des selles humaines qui permet de stabiliser l’ADN bactérien à température ambiante, une technique d’extraction de cet ADN et un protocole de séquençage qui permettent d’apporter une réponse quant au statut microbien du microbiote chez nos patients. J’ai réalisé une première validation de cette technologie par comparaison avec une autre technologie, le séquençage « SOLID », sur une même cohorte. J’ai pu obtenir la même stratification des patients en fonction de leurs diversité microbienne intestinale.

Published
2018

19. Angiotensin II and EGF receptor cross-talk in chronic kidney diseases: a new therapeutic approach

Author

Lautrette, Alexandre, Li, Shunqiang, Alili, Rohia, Sunnarborg, Susan W, Burtin, Martine, Lee, David C, Friedlander, Gerard, and Terzi, Fabiola

Abstract

Mechanisms of progression of chronic renal diseases, a major healthcare burden, are poorly understood. Angiotensin II (AngII), the major renin-angiotensin system effector, is known to be involved in renal deterioration, but the molecular pathways are still unknown. Here, we show that mice overexpressing a dominant negative isoform of epidermal growth factor receptor (EGFR) were protected from renal lesions during chronic AngII infusion. Transforming growth factor-[alpha] (TGF-[alpha]) and its sheddase, TACE (also known as ADAM17), were induced by AngII treatment, TACE was redistributed to apical membranes and EGFR was phosphorylated. AngII-induced lesions were substantially reduced in mice lacking TGF-[alpha] or in mice given a specific TACE inhibitor. Pharmacologic inhibition of AngII prevented TGF-[alpha] and TACE accumulation as well as renal lesions after nephron reduction. These findings indicate a crucial role for AngII-dependent EGFR transactivation in renal deterioration and identify in TACE inhibitors a new therapeutic strategy for preventing progression of chronic renal diseases., Author(s): Alexandre Lautrette [1]; Shunqiang Li [2]; Rohia Alili [1]; Susan W Sunnarborg [2]; Martine Burtin [1]; David C Lee [2]; Gerard Friedlander [1]; Fabiola Terzi (corresponding author) [1] Regardless [...]

Published
2005
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25. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child and adult BMI

Author

Alves, Alexessander Couto, De Silva, Maneka, Karhunen, Ville, Sovio, Ulla, Das, Shikta, Taal, H Rob, Warrington, Nicole M., Lewin, Alex, Kaakinen, Marika, Cousminer, Diana L., Thiering, Elisabeth, Timpson, Nicholas, Bond, Tom A, Lowry, Estelle, Brown, Christopher, Estivill, Xavier, Lindi, Virpi, Bradfield, Jonathan P, Geller, Frank, Speed, Doug, Coin, Lachlan J M, Loh, Marie, Barton, Sheila J, Beilin, Lawrence J, Bisgaard, Hans, Bonnelykke, Klaus, Alili, Rohia, Hatoum, Ida, Schramm, Katharina, Cartwright, Rufus, Charles, Marie-Aline, Salerno, Vincenzo, Clement, Karine, Claringbould, Annique, van Duijn, CM, Moltchanova, Elena, Frayling, Timothy, Freathy, Rachel, Lawlor, Debbie, Ring, Susan, Davey Smith, George, McCarthy, Mark I, and Järvelin, Marjo-Riitta

Abstract

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

Published
2019

26. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Author

Da Silva Couto Alves, Alexessander, De Silva, N. Maneka G., Karhunen, Ville, Sovio, Ulla, Das, Shikta, Taal, H. Rob, Warrington, Nicole M., Lewin, Alexandra M., Kaakinen, Marika, Cousminer, Diana L., Thiering, Elisabeth, Timpson, Nicholas J., Bond, Tom A., Lowry, Estelle, Brown, Christopher D., Estivill, Xavier, Lindi, Virpi, Bradfield, Jonathan P., Geller, Frank, Speed, Doug, Coin, Lachlan J. M., Loh, Marie, Barton, Sheila J., Beilin, Lawrence J., Bisgaard, Hans, Bonnelykke, Klaus, Alili, Rohia, Hatoum, Ida J., Schramm, Katharina, Cartwright, Rufus, Charles, Marie-Aline, Salerno, Vincenzo, Clement, Karine, Claringbould, Annique A.J, Consortium, BIOS, van Duijin, Cornelia M., Moltchanova, Elena, Eriksson, Johan G., Elks, Cathy, Feenstra, Bjarke, Flexeder, Claudia, Franks, Stephen, Frayling, Timothy M., Freathy, Rachel M., Elliot, Paul, Widen, Elisabeth, Hakonarson, Hakon, Hattersley, Andrew T., Rodriguez, Alina, Banterle, Marco, Heinrich, Joachim, Heude, Barbara, Holloway, John W., Hofman, Albert, Hypponen, Elina, Inskip, Hazel, Kaplan, Lee M., Hedman, Asa K., Laara, Esa, Prokisch, Holger, Grallert, Harald, Lakka, Timo A., Lawlor, Debbie A., Melbye, Mads, Ahluwalia, Tarunveer S., Marinelli, Marcella, Millwood, Iona Y., Palmer, Lyle J., Pennell, Craig E., Perry, John R., Ring, Susan M., Savolainen, Markku J., Rivadeneira, Fernando, Standl, Marie, Sunyer, Jordi, Tiesler, Carla M.T, Uitterlinden, Andre G., Schierding, William, O'Sullivan, Justin M., Prokopenko, Inga, Herzig, Karl-Heinz, Smith, George Davey, O'Reilly, Paul, Felix, Janine F., Buxton, Jessica L., Blakemore, Alexandra L. F, Ong, Ken K., Jaddoe, Vincent W.V, Grant, Struan F.A, Sebert, Sylvain, McCarthy, Mark L., and Jarvelin, Marjo-Riitta

Abstract

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

Published
2019

27. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Author

Couto Alves, Alexessander, De Silva, N. Maneka G., Karhunen, Ville, Sovio, Ulla, Das, Shikta, Taal, H. Rob, Warrington, Nicole M., Lewin, Alexandra M., Kaakinen, Marika, Cousminer, Diana L., Thiering, Elisabeth, Timpson, Nicholas J., Bond, Tom A., Lowry, Estelle, Brown, Christopher D., Estivill, Xavier, Lindi, Virpi, Bradfield, Jonathan P., Geller, Frank, Speed, Doug, Coin, Lachlan J. M., Loh, Marie, Barton, Sheila J., Beilin, Lawrence J., Bisgaard, Hans, Bønnelykke, Klaus, Alili, Rohia, Hatoum, Ida J., Schramm, Katharina, Cartwright, Rufus, Charles, Marie-Aline, Salerno, Vincenzo, Clément, Karine, Claringbould, Annique A. J., van Duijn, Cornelia M., Moltchanova, Elena, Eriksson, Johan G., Elks, Cathy, Feenstra, Bjarke, Flexeder, Claudia, Franks, Stephen, Frayling, Timothy M., Freathy, Rachel M., Elliott, Paul, Widén, Elisabeth, Hakonarson, Hakon, Hattersley, Andrew T., Rodriguez, Alina, Banterle, Marco, Heinrich, Joachim, Heude, Barbara, Holloway, John W., Hofman, Albert, Hyppönen, Elina, Inskip, Hazel, Kaplan, Lee M., Hedman, Asa K., Läärä, Esa, Prokisch, Holger, Grallert, Harald, Lakka, Timo A., Lawlor, Debbie A., Melbye, Mads, Ahluwalia, Tarunveer S., Marinelli, Marcella, Millwood, Iona Y., Palmer, Lyle J., Pennell, Craig E., Perry, John R., Ring, Susan M., Savolainen, Markku J., Rivadeneira, Fernando, Standl, Marie, Sunyer, Jordi, Tiesler, Carla M. T., Uitterlinden, Andre G., Schierding, William, O’Sullivan, Justin M., Prokopenko, Inga, Herzig, Karl-Heinz, Smith, George Davey, O'Reilly, Paul, Felix, Janine F., Buxton, Jessica L., Blakemore, Alexandra I. F., Ong, Ken K., Jaddoe, Vincent W. V., Grant, Struan F. A., Sebert, Sylvain, McCarthy, Mark I., and Järvelin, Marjo-Riitta

Subjects
ddc
Published
2018

28. Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency

Author

Collet, Tinh-Hai, Dubern, Béatrice, Mokrosinski, Jacek, Connors, Hillori, Keogh, Julia M., Mendes de Oliveira, Edson, Henning, Elana, Poitou-Bernert, Christine, Oppert, Jean-Michel, Tounian, Patrick, Marchelli, Florence, Alili, Rohia, Le Beyec, Johanne, Pépin, Dominique, Lacorte, Jean-Marc, Gottesdiener, Andrew, Bounds, Rebecca, Sharma, Shubh, Folster, Cathy, Henderson, Bart, O'Rahilly, Stephen, Stoner, Elizabeth, Gottesdiener, Keith, Panaro, Brandon L., Cone, Roger D., Clément, Karine, Farooqi, I. Sadaf, and Van der Ploeg, Lex H.T.

Published
2017
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29. Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity

Author

Nektarios Tavernarakis, Mireia Niso-Santano, Lorenzo Galluzzi, Violeta Raverdy, Friedemann Loos, Guido Kroemer, François Pattou, Céline Cruciani-Guglielmacci, Patricia Boya, Justine Lallement, Frank Madeo, Jessica Denom, Ignacio Ramírez-Pardo, Karine Clément, Christophe Magnan, Isabelle Martins, Sylvère Durand, Raphaël G. P. Denis, Noélie Bossut, Maria Chiara Maiuri, Véronique Pelloux, Robert Caiazzo, Valentina Sica, Erwan Boedec, Alili Rohia, Stéphanie Migrenne-Li, José Manuel Bravo-San Pedro, Jonathan Pol, Nicolas Ramoz, Fernando Aranda, Philip Gorwood, Gerasimos Anagnostopoulos, Fanny Aprahamian, Carlos López-Otín, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), Université Paris-Saclay, Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigaciones Biológicas (CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Hôpital Sainte-Anne-Université Paris Descartes - Paris 5 (UPD5), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Apoptose, cancer et immunité (U848), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Weill Medical College of Cornell University [New York], Sandra and Edward Meyer Cancer Center [New-York], Yale University School of Medicine, BioTechMed-Graz, Graz University of Technology [Graz] (TU Graz)-Medical University Graz-Karl-Franzens-Universität [Graz, Autriche], Institute of Molecular Biosciences, Karl-Franzens-Universität [Graz, Autriche], University of Crete [Heraklion] (UOC), Institute of Molecular Biology and Biotechnology (IMBB-FORTH), Foundation for Research and Technology - Hellas (FORTH), Universidad de Oviedo [Oviedo], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), University of Science & Technology of China [Suzhou], Karolinska Institutet [Stockholm], The authors thank CRC Core Facilities (CGB, CHIC, and CEF). G.K. is supported by the Ligue Contre le Cancer (équipe labelisée), Agence National de la Recherche (ANR) – projets blancs, Cancéropôle Île-de-France, Chancelerie Des universités de Paris (Legs Poix), the European Research Council (ERC), Inserm Transfert, Fondation Carrefour, Institut National du Cancer (INCa), Inserm (HTE), Institut Universitaire de France, Leducq Foundation, the Labex immuno-Oncology, the RHU Torino Lumière, the Seattle Foundation, and the SIRICs SOCRATE and CARPEM. C.M. and C.C.-G. are supported by Agence National de la Recherche (ANR-16-CE14-0026, fat4brain proposal), C.L.-O. is supported by 'Juan de Madariaga fellowship', S.B. is supported by the Swedish Research Council Vetenskapsrådet (2015-05468) and the Austrian Science Fund FWF (P27183-B24), and F.M. is supported by the Austrian Science Fund FWF (grants P23490-B20, P29262, P24381, P29203, and P27893), DKplus Metabolic and Cardiovascular Diseases (W1226), Austrian Science Ministry, Karl Franzens University ('Unkonventionelle Forschung' and 'flysleep'), NAWI Graz, and BioTechMed-Graz flagship project 'EPIAge.' K.C. is supported by ANR MICRO-Obes and AP/HP (PHRC Microbaria). L.G. is supported by an intramural startup from the Department of Radiation Oncology of Weill Cornell Medical College (New York, US) and by Sotio a.c. (Prague, Czech Republic)., The authors thank PreclinICAN (Institute of Cardiometabolism and Nutrition, IHU-ICAN, Paris, France) and 'Plateforme Imageries du Vivant' INSERM UMR 970 (PARCC-HEGP) for analyses of mouse whole-body composition and Functional & Physiological Exploration Platform (FPE) of the Unit 'Biologie Fonctionnelle et Adaptative' (University Paris Diderot, Sorbonne Paris Cité, BFA, UMR 8251 CNRS, Paris, France) for metabolic analyses., Ligue Nationale contre le Cancer (France), Agence Nationale de la Recherche (France), Chancellerie des Universités de Paris, European Research Council, Institut National du Cancer (France), Fondation Leducq, Swedish Research Council, Austrian Science Fund, Federal Ministry of Science, Research and Economy (Austria), Bravo-San-Pedro, José Manuel [0000-0002-5781-1133], Sica, Valentina [0000-0003-2770-5847], Martins, Isabelle [0000-0003-0885-613X], Pol, Jonathan G. [0000-0002-8355-7562], Loos, Friedemann [0000-0002-5976-5978], Maiuri, Maria Chiara [0000-0001-9760-7674], Niso-Santano, Mireia [0000-0002-6506-422X], Aranda, Fernando [0000-0002-9364-474X], Gorwood, Philip [0000-0003-1845-3676], Ramoz, Nicolas [0000-0002-8070-9938], Cleḿent, Karine [0000-0002-2489-3355], Pelloux, Véronique [0000-0003-3630-4746], Raverdy, Violeta [0000-0001-5754-2028], Denis, Raphaël G.P. [0000-0002-7677-7460], Boya, Patricia [0000-0003-3045-951X], Galluzzi, Lorenzo [0000-0003-2257-8500 ], Madeo, Frank [0000-0002-5070-1329], Cruciani-Guglielmacci, Céline [0000-0002-2562-5360], Tavernarakis, Nektarios [0000-0002-5253-1466 ], López-Otín, Carlos [0000-0001-6964-1904], Magnan, Christophe [0000-0002-7044-2571], Kroemer, Guido [0000-0002-9334-4405], CCSD, Accord Elsevier, Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Yale School of Medicine [New Haven, Connecticut] (YSM), Graz University of Technology [Graz] (TU Graz)-Karl-Franzens-Universität Graz-Medical University Graz, Karl-Franzens-Universität Graz, École Pratique des Hautes Études (EPHE), Centre de Psychiatrie et Neurosciences (U894), ANR-16-CE14-0026,Fat4Brain,Le métabolisme des lipides dans le cerveau est un regulateur essentiel de l'homéostasie énergétique(2016), Bravo-San Pedro, J. M., Sica, V., Martins, I., Pol, J., Loos, F., Maiuri, M. C., Durand, S., Bossut, N., Aprahamian, F., Anagnostopoulos, G., Niso-Santano, M., Aranda, F., Ramirez-Pardo, I., Lallement, J., Denom, J., Boedec, E., Gorwood, P., Ramoz, N., Clement, K., Pelloux, V., Rohia, A., Pattou, F., Raverdy, V., Caiazzo, R., Denis, R. G. P., Boya, P., Galluzzi, L., Madeo, F., Migrenne-Li, S., Cruciani-Guglielmacci, C., Tavernarakis, N., Lopez-Otin, C., Magnan, C., Kroemer, G., Bravo-San-Pedro, José Manuel, Sica, Valentina, Martins, Isabelle, Pol, Jonathan G., Loos, Friedemann, Maiuri, Maria Chiara, Niso-Santano, Mireia, Aranda, Fernando, Gorwood, Philip, Ramoz, Nicolas, Cleḿent, Karine, Pelloux, Véronique, Raverdy, Violeta, Denis, Raphaël G.P., Boya, Patricia, Galluzzi, Lorenzo, Madeo, Frank, Cruciani-Guglielmacci, Céline, Tavernarakis, Nektarios, López-Otín, Carlos, Magnan, Christophe, and Kroemer, Guido

Subjects
Male, 0301 basic medicine, obesity, Anorexia Nervosa, Physiology, Mice, Obese, Weight Gain, Eating, Mice, 0302 clinical medicine, lipid metabolism, Acyl-CoA-binding protein, Beta oxidation, media_common, Diazepam Binding Inhibitor, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 2. Zero hunger, 0303 health sciences, Leptin Deficiency, Chemistry, Fatty Acids, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Anorexia, 3. Good health, anorexia, Lipogenesis, Female, medicine.symptom, Human, autophagy, medicine.medical_specialty, media_common.quotation_subject, Context (language use), Cell Line, 03 medical and health sciences, Internal medicine, Macroautophagy, Weight Loss, Autophagy, medicine, Animals, Humans, Obesity, Molecular Biology, 030304 developmental biology, Animal, Lipogenesi, Appetite, Cell Biology, Weight Lo, Mice, Inbred C57BL, Lipid metabolism, 030104 developmental biology, Endocrinology, Fatty Acid, 030217 neurology & neurosurgery
Abstract

24 p.-6 fig.-1 tab.-1 graph. abst., Autophagy facilitates the adaptation to nutritional stress. Here, we show that short-term starvation of cultured cells or mice caused the autophagy-dependent cellular release of acyl-CoA-binding protein (ACBP, also known as diazepam-binding inhibitor, DBI) and consequent ACBP-mediated feedback inhibition of autophagy. Importantly, ACBP levels were elevated in obese patients and reduced in anorexia nervosa. In mice, systemic injection of ACBP protein inhibited autophagy, induced lipogenesis, reduced glycemia, and stimulated appetite as well as weight gain. We designed three approaches to neutralize ACBP, namely, inducible whole-body knockout, systemic administration of neutralizing antibodies, and induction of antiACBP autoantibodies in mice. ACBP neutralization enhanced autophagy, stimulated fatty acid oxidation, inhibited appetite, reduced weight gain in the context of a high-fat diet or leptin deficiency, and accelerated weight loss in response to dietary changes. In conclusion, neutralization of ACBP might constitute a strategy for treating obesity and its co-morbidities., G.K. is supported by the Ligue Contre le Cancer (équipe labelisée); Agence National de la Recherche (ANR) – projets blancs; Cancéropôle Île-de-France; Chancelerie Des universités de Paris (Legs Poix); the European Research Council (ERC); Inserm Transfert, Fondation Carrefour; Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; Leducq Foundation; the Labex immuno-Oncology; the RHU Torino Lumière; the Seattle Foundation; and the SIRICs SOCRATE and CARPEM. C.M. and C.C.-G. are supported by Agence National de la Recherche (ANR-16-CE14-0026, fat4brain proposal); C.L.-O. is supported by “Juan de Madariaga fellowship”; S.B. is supported by the Swedish Research Council Vetenskapsrådet (2015-05468) and the Austrian Science Fund FWF (P27183-B24); and F.M. is supported by the Austrian Science Fund FWF (grants P23490-B20, P29262, P24381, P29203, and P27893), DKplus Metabolic and Cardiovascular Diseases (W1226), Austrian Science Ministry, Karl Franzens University (“Unkonventionelle Forschung” and “flysleep”), NAWI Graz, and BioTechMed-Graz flagship project “EPIAge.” K.C. is supported by ANR MICRO-Obes and AP/HP (PHRC Microbaria). L.G. is supported by an intramural startup from the Department of Radiation Oncology of Weill Cornell Medical College (New York, US) and by Sotio a.c. (Prague, Czech Republic).

Published
2019

30. Human catalase gene promoter haplotype and cardiometabolic improvement after bariatric surgery

Author

Alili, Rohia, primary, Nivet-Antoine, Valérie, additional, Saldmann, Antonin, additional, Golmard, Jean-Louis, additional, Cottart, Charles-Henry, additional, Laguillier, Christelle, additional, Giral, Philippe, additional, Beaudeux, Jean-Louis, additional, Bouillot, Jean-Luc, additional, Poitou, Christine, additional, Clément, Karine, additional, and Hébert-Schuster, Marylise, additional

Published
2018
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31. Genetic architecture of early childhood growth phenotypes gives insights into their link with later obesity

Author

De Silva, N. Maneka G., primary, Sebert, Sylvain, additional, Alves, Alexessander Couto, additional, Sovio, Ulla, additional, Das, Shikta, additional, Taal, Rob, additional, Warrington, Nicole M., additional, Lewin, Alexandra M., additional, Kaakinen, Marika, additional, Cousminer, Diana, additional, Thiering, Elisabeth, additional, Timpson, Nicholas J., additional, Karhunen, Ville, additional, Bond, Tom, additional, Estivill, Xavier, additional, Lindi, Virpi, additional, Bradfield, Jonathan P., additional, Geller, Frank, additional, Coin, Lachlan J.M., additional, Loh, Marie, additional, Barton, Sheila J., additional, Beilin, Lawrence J., additional, Bisgaard, Hans, additional, Bønnelykke, Klaus, additional, Alili, Rohia, additional, Hatoum, Ida J., additional, Schramm, Katharina, additional, Cartwright, Rufus, additional, Charles, Marie-Aline, additional, Salerno, Vincenzo, additional, Clément, Karine, additional, van Duijn, Cornelia M., additional, Moltchanova, Elena, additional, Eriksson, Johan G., additional, Elks, Cathy, additional, Feenstra, Bjarke, additional, Flexeder, Claudia, additional, Franks, Stephen, additional, Frayling, Timothy M., additional, Freathy, Rachel M., additional, Elliott, Paul, additional, Widén, Elisabeth, additional, Hakonarson, Hakon, additional, Hattersley, Andrew T., additional, Rodriguez, Alina, additional, Banterle, Marco, additional, Heinrich, Joachim, additional, Heude, Barbara, additional, Holloway, John W., additional, Hofman, Albert, additional, Hyppönen, Elina, additional, Inskip, Hazel, additional, Kaplan, Lee M., additional, Hedman, Asa K., additional, Läärä, Esa, additional, Prokisch, Holger, additional, Grallert, Harald, additional, Lakka, Timo A., additional, Lawlor, Debbie A., additional, Melbye, Mads, additional, Ahluwalia, Tarunveer S., additional, Marinelli, Marcella, additional, Millwood, Iona Y., additional, Palmer, Lyle J., additional, Pennell, Craig E., additional, Perry, John R., additional, Ring, Susan M., additional, Savolainen, Markku, additional, Stefansson, Kari, additional, Thorleifsson, Gudmar, additional, Rivadeneira, Fernando, additional, Standl, Marie, additional, Sunyer, Jordi, additional, Tiesler, Carla M.T., additional, Uitterlinden, Andre G., additional, Prokopenko, Inga, additional, Herzig, Karl-Heinz, additional, Smith, George Davey, additional, O'Reilly, Paul, additional, Felix, Janine F., additional, Buxton, Jessica L., additional, Blakemore, Alexandra I.F., additional, Ong, Ken K., additional, Grant, Struan F.A., additional, Jaddoe, Vincent W.V., additional, McCarthy, Mark I., additional, and Järvelin, Marjo-Riitta, additional

Published
2017
Full Text
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32. Bariatric Surgery Induces Disruption in Inflammatory Signaling Pathways Mediated by Immune Cells in Adipose Tissue: A RNA-Seq Study

Author

Poitou, Christine, Perret, Claire, Mathieu, François, Truong, Vinh, Blum, Yuna, Durand, Hervé, Alili, Rohia, Chelghoum, Nadjim, Pelloux, Véronique, Aron-Wisnewsky, Judith, Torcivia, Adriana, Bouillot, Jean-Luc, Parks, Brian W., Ninio, Ewa, Clément, Karine, Tiret, Laurence, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University of California [Los Angeles] (UCLA), University of California (UC), Plateforme Post-génomique de la Pitié-Salpêtrière (P3S), UMS omique (OMIQUE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of general, dugestive and metabolic surgery, Hôpital Ambroise Paré [AP-HP], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of California, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Adult, Inflammation, Gene Expression Profiling, lcsh:R, Bariatric Surgery, Computational Biology, lcsh:Medicine, Middle Aged, Disease Models, Animal, Mice, Adipose Tissue, Gene Expression Regulation, Animals, Cluster Analysis, Humans, Female, Gene Regulatory Networks, lcsh:Q, Interferons, Obesity, lcsh:Science, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article, Signal Transduction
Abstract

International audience; BackgroundBariatric surgery is associated to improvements in obesity-associated comorbidities thought to be mediated by a decrease of adipose inflammation. However, the molecular mechanisms behind these beneficial effects are poorly understood.Methodology/Principal FindingsWe analyzed RNA-seq expression profiles in adipose tissue from 22 obese women before and 3 months after surgery. Of 15,972 detected genes, 1214 were differentially expressed after surgery at a 5% false discovery rate. Upregulated genes were mostly involved in the basal cellular machinery. Downregulated genes were enriched in metabolic functions of adipose tissue. At baseline, 26 modules of coexpressed genes were identified. The four most stable modules reflected the innate and adaptive immune responses of adipose tissue. A first module reflecting a non-specific signature of innate immune cells, mainly macrophages, was highly conserved after surgery with the exception of DUSP2 and CD300C. A second module reflected the adaptive immune response elicited by T lymphocytes; after surgery, a disconnection was observed between genes involved in T-cell signaling and mediators of the signal transduction such as CXCR1, CXCR2, GPR97, CCR7 and IL7R. A third module reflected neutrophil-mediated inflammation; after surgery, several genes were dissociated from the module, including S100A8, S100A12, CD300E, VNN2, TUBB1 and FAM65B. We also identified a dense network of 19 genes involved in the interferon-signaling pathway which was strongly preserved after surgery, with the exception of DDX60, an antiviral factor involved in RIG-I-mediated interferon signaling. A similar loss of connection was observed in lean mice compared to their obese counterparts.Conclusions/SignificanceThese results suggest that improvements of the inflammatory state following surgery might be explained by a disruption of immuno-inflammatory cascades involving a few crucial molecules which could serve as potential therapeutic targets.

Published
2015

33. Adipocyte ATP-Binding Cassette G1 Promotes Triglyceride Storage, Fat Mass Growth, and Human Obesity

Author

Frisdal, Eric, primary, Le Lay, Soazig, additional, Hooton, Henri, additional, Poupel, Lucie, additional, Olivier, Maryline, additional, Alili, Rohia, additional, Plengpanich, Wanee, additional, Villard, Elise F., additional, Gilibert, Sophie, additional, Lhomme, Marie, additional, Superville, Alexandre, additional, Miftah-Alkhair, Lobna, additional, Chapman, M. John, additional, Dallinga-Thie, Geesje M., additional, Venteclef, Nicolas, additional, Poitou, Christine, additional, Tordjman, Joan, additional, Lesnik, Philippe, additional, Kontush, Anatol, additional, Huby, Thierry, additional, Dugail, Isabelle, additional, Clement, Karine, additional, Guerin, Maryse, additional, and Le Goff, Wilfried, additional

Published
2014
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34. Valsartan Improves Adipose Tissue Function in Humans with Impaired Glucose Metabolism: A Randomized Placebo-Controlled Double-Blind Trial

Author

Goossens, Gijs H., primary, Moors, Chantalle C. M., additional, van der Zijl, Nynke J., additional, Venteclef, Nicolas, additional, Alili, Rohia, additional, Jocken, Johan W. E., additional, Essers, Yvonne, additional, Cleutjens, Jack P., additional, Clément, Karine, additional, Diamant, Michaela, additional, and Blaak, Ellen E., additional

Published
2012
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35. NHERF1Mutations and Responsiveness of Renal Parathyroid Hormone

Author

Karim, Zoubida, primary, Gérard, Bénédicte, additional, Bakouh, Naziha, additional, Alili, Rohia, additional, Leroy, Christine, additional, Beck, Laurent, additional, Silve, Caroline, additional, Planelles, Gabrielle, additional, Urena-Torres, Pablo, additional, Grandchamp, Bernard, additional, Friedlander, Gérard, additional, and Prié, Dominique, additional

Published
2008
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36. Seven Novel Deleterious LEPRMutations Found in Early-Onset Obesity: a ΔExon6–8 Shared by Subjects From Reunion Island, France, Suggests a Founder Effect

Author

Huvenne, Hélène, Le Beyec, Johanne, Pépin, Dominique, Alili, Rohia, Kherchiche, Patricia Pigeon, Jeannic, Erwan, Frelut, Marie-Laure, Lacorte, Jean-Marc, Nicolino, Marc, Viard, Amélie, Laville, Martine, Ledoux, Séverine, Tounian, Patrick, Poitou, Christine, Dubern, Béatrice, and Clément, Karine

Abstract

Context:Infrequent mutations have been reported in the leptin receptor (LEPR) gene in humans with morbid obesity and endocrine disorders. However LEPRmutations are rarely examined in large populations from different ethnicities in a given country.Objective:We estimated the prevalence of LEPRmutations in French patients with severe obesity and evaluated mutated patients' phenotype.Design and Patients:We sequenced the LEPRgene in 535 morbidly obese French participants. We conducted clinical investigations to determine whether individuals with a novel shared mutation display particular characteristics relative to obesity history, body composition, hormonal functions, and the outcome of bariatric surgery.Results:We identified 12 patients with a novel LEPRmutation (p.C604G, p.L786P, p.H800_N831del, p.Y422H, p.T711NfsX18, p.535–1G>A, p.P166CfsX7). Six unrelated subjects were carriers of the p.P166CfsX7 mutation leading to deletion overlapping exons 6 to 8. All subjects originated from Reunion Island (France). Their clinical features (severe early-onset obesity, food impulsivity, and hypogonadotropic hypogonadism) did not differ from other new LEPRmutation carriers. Results concerning weight loss surgery were inconsistent in homozygous LEPRmutation carriers. Heterozygous LEPRmutation carriers exhibited variable severity of obesity and no endocrine abnormality.Conclusion:Among seven newly discovered LEPRmutations in this French obese population, we identified a LEPRframeshift mutation shared by six subjects from Reunion Island. This observation suggests a founder effect in this Indian Ocean island with high prevalence of obesity and supports a recommendation for systematic screening for this mutation in morbidly obese subjects in this population.

Published
2015
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37. Fate and Complex Pathogenic Effects of Dioxins and Polychlorinated Biphenyls in Obese Subjects before and after Drastic Weight Loss.

Author

Min-Ji Kim, Marchand, Philippe, Henegar, Corneliu, Antignac, Jean-Philippe, Alili, Rohia, Poitou, Christine, Bouillot, Jean-Luc, Basdevant, Arnaud, Le Bizec, Bruno, Barouki, Robert, and Clément, Karine

Subjects
BLOOD testing, BARIATRIC surgery, ADIPOSE tissues, ANALYSIS of variance, COMPARATIVE studies, COMPUTER software, FACTOR analysis, GENE expression, MULTIVARIATE analysis, OBESITY, POLLUTANTS, POLYCHLORINATED biphenyls, STATISTICS, WEIGHT loss, X-ray densitometry in medicine, DATA analysis, BODY mass index
Abstract

BACKGROUND: In humans, persistent organic pollutants (POPs) are stored primarily in adipose tissue. Their total body burden and their contribution to obesity-associated diseases remain unclear. OBJECTIVES: We characterized POP total body burden and their redistribution in obese individuals before and after drastic weight loss and compared these values with a variety of molecular, biological, and clinical parameters. Methods: Seventy-one obese subjects were enrolled and underwent bariatric surgery. Blood and adipose tissue samples were obtained at different times from these individuals as well as from 18 lean women. RESULTS: POP content (17 dioxins/furans and 18 polychlorinated biphenyl congeners) in different adipose tissue territories was similar, allowing us to assess total POP body burden from a single biopsy. Total POP body burden was 2 to 3 times higher in obese than in lean individuals. We also found increased expression of some POP target genes in obese adipose tissue. Drastic weight loss led to increased serum POPs and, within 6-12 months, to a significant 15% decrease in total polychlorinated biphenyl body burden. Importantly, serum POP levels were positively correlated with liver toxicity markers and lipid parameters, independently of age and body mass index. CONCLUSIONS: POP content in adipose tissue and serum correlate with biological markers of obesity- related dysfunctions. Drastic weight loss leads to a redistribution of POPs and to a moderate decrease of their total body burden. [ABSTRACT FROM AUTHOR]

Published
2011
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38. Characterization of the Gut Microbiota in Individuals with Overweight or Obesity during a Real-World Weight Loss Dietary Program: A Focus on the Bacteroides 2 Enterotype.

Author

Alili, Rohia, Belda, Eugeni, Fabre, Odile, Pelloux, Véronique, Giordano, Nils, Legrand, Rémy, Bel Lassen, Pierre, Swartz, Timothy D., Zucker, Jean-Daniel, and Clément, Karine

Subjects
WEIGHT loss, GUT microbiome, BACTEROIDES, LOW-calorie diet, HIGH-protein diet
Abstract

Background: Dietary intervention is a cornerstone of weight loss therapies. In obesity, a dysbiotic gut microbiota (GM) is characterized by high levels of Bacteroides lineages and low diversity. We examined the GM composition changes, including the Bacteroides 2 enterotype (Bact2), in a real-world weight loss study in subjects following a high-protein hypocaloric diet with or without a live microorganisms (LMP) supplement. Method: 263 volunteers were part of this real-world weight loss program. The first phase was a high-protein low-carbohydrate calorie restriction diet with or without LMP supplements. Fecal samples were obtained at baseline and after 10% weight loss for 163 subjects. Metagenomic profiling was obtained by shotgun sequencing. Results: At baseline, the Bact2 enterotype was more prevalent in subjects with aggravated obesity and metabolic alterations. After weight loss, diversity increased and Bact2 prevalence decreased in subjects with lower GM diversity at baseline, notably in LMP consumers. Significant increases in Akkermansia muciniphila and Parabacteroides distasonis and significant decreases of Eubacterium rectale, Streptococcus thermophilus and Bifidobacterial lineages were observed after weight loss. Conclusions: Baseline microbiome composition is associated with differential changes in GM diversity and Bact2 enterotype prevalence after weight loss. Examining these signatures could drive future personalized nutrition efforts towards more favorable microbiome compositions. [ABSTRACT FROM AUTHOR]

Published
2022
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39. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Author

Couto Alves, Alexessander, De Silva, N Maneka G, Karhunen, Ville, Sovio, Ulla, Das, Shikta, Taal, H Rob, Warrington, Nicole M, Lewin, Alexandra M, Kaakinen, Marika, Cousminer, Diana L, Thiering, Elisabeth, Timpson, Nicholas J, Bond, Tom A, Lowry, Estelle, Brown, Christopher D, Estivill, Xavier, Lindi, Virpi, Bradfield, Jonathan P, Geller, Frank, Speed, Doug, Coin, Lachlan JM, Loh, Marie, Barton, Sheila J, Beilin, Lawrence J, Bisgaard, Hans, Bønnelykke, Klaus, Alili, Rohia, Hatoum, Ida J, Schramm, Katharina, Cartwright, Rufus, Charles, Marie-Aline, Salerno, Vincenzo, Clément, Karine, Claringbould, Annique AJ, Van Duijn, Cornelia M, Moltchanova, Elena, Eriksson, Johan G, Elks, Cathy, Feenstra, Bjarke, Flexeder, Claudia, Franks, Stephen, Frayling, Timothy M, Freathy, Rachel M, Elliott, Paul, Widén, Elisabeth, Hakonarson, Hakon, Hattersley, Andrew T, Rodriguez, Alina, Banterle, Marco, Heinrich, Joachim, Heude, Barbara, Holloway, John W, Hofman, Albert, Hyppönen, Elina, Inskip, Hazel, Kaplan, Lee M, Hedman, Asa K, Läärä, Esa, Prokisch, Holger, Grallert, Harald, Lakka, Timo A, Lawlor, Debbie A, Melbye, Mads, Ahluwalia, Tarunveer S, Marinelli, Marcella, Millwood, Iona Y, Palmer, Lyle J, Pennell, Craig E, Perry, John R, Ring, Susan M, Savolainen, Markku J, Rivadeneira, Fernando, Standl, Marie, Sunyer, Jordi, Tiesler, Carla MT, Uitterlinden, Andre G, Schierding, William, O’Sullivan, Justin M, Prokopenko, Inga, Herzig, Karl-Heinz, Smith, George Davey, O'Reilly, Paul, Felix, Janine F, Buxton, Jessica L, Blakemore, Alexandra IF, Ong, Ken K, Jaddoe, Vincent WV, Grant, Struan FA, Sebert, Sylvain, McCarthy, Mark I, and Järvelin, Marjo-Riitta

Subjects
2. Zero hunger, Adult, Male, Pharmacogenomic Variants, Quantitative Trait Loci, Intracellular Signaling Peptides and Proteins, Infant, Genomics, Polymorphism, Single Nucleotide, Body Mass Index, Quantitative Trait, Heritable, Humans, Receptors, Leptin, Female, Genetic Predisposition to Disease, Longitudinal Studies, Growth Charts, Child, Genetic Association Studies, Adaptor Proteins, Signal Transducing, Genome-Wide Association Study
Abstract

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

40. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI.

Author

Couto Alves A, De Silva NMG, Karhunen V, Sovio U, Das S, Taal HR, Warrington NM, Lewin AM, Kaakinen M, Cousminer DL, Thiering E, Timpson NJ, Bond TA, Lowry E, Brown CD, Estivill X, Lindi V, Bradfield JP, Geller F, Speed D, Coin LJM, Loh M, Barton SJ, Beilin LJ, Bisgaard H, Bønnelykke K, Alili R, Hatoum IJ, Schramm K, Cartwright R, Charles MA, Salerno V, Clément K, Claringbould AAJ, van Duijn CM, Moltchanova E, Eriksson JG, Elks C, Feenstra B, Flexeder C, Franks S, Frayling TM, Freathy RM, Elliott P, Widén E, Hakonarson H, Hattersley AT, Rodriguez A, Banterle M, Heinrich J, Heude B, Holloway JW, Hofman A, Hyppönen E, Inskip H, Kaplan LM, Hedman AK, Läärä E, Prokisch H, Grallert H, Lakka TA, Lawlor DA, Melbye M, Ahluwalia TS, Marinelli M, Millwood IY, Palmer LJ, Pennell CE, Perry JR, Ring SM, Savolainen MJ, Rivadeneira F, Standl M, Sunyer J, Tiesler CMT, Uitterlinden AG, Schierding W, O'Sullivan JM, Prokopenko I, Herzig KH, Smith GD, O'Reilly P, Felix JF, Buxton JL, Blakemore AIF, Ong KK, Jaddoe VWV, Grant SFA, Sebert S, McCarthy MI, and Järvelin MR

Subjects
Adaptor Proteins, Signal Transducing genetics, Adult, Child, Female, Genetic Predisposition to Disease, Genomics, Growth Charts, Humans, Infant, Intracellular Signaling Peptides and Proteins, Longitudinal Studies, Male, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Receptors, Leptin genetics, Body Mass Index, Genetic Association Studies, Genome-Wide Association Study, Quantitative Trait Loci, Quantitative Trait, Heritable
Abstract

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

Published
2019
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41. Bariatric Surgery Induces Disruption in Inflammatory Signaling Pathways Mediated by Immune Cells in Adipose Tissue: A RNA-Seq Study.

Author

Poitou C, Perret C, Mathieu F, Truong V, Blum Y, Durand H, Alili R, Chelghoum N, Pelloux V, Aron-Wisnewsky J, Torcivia A, Bouillot JL, Parks BW, Ninio E, Clément K, and Tiret L

Subjects
Adult, Animals, Cluster Analysis, Computational Biology, Disease Models, Animal, Female, Gene Expression Profiling, Gene Expression Regulation, Gene Regulatory Networks, Humans, Inflammation genetics, Interferons metabolism, Mice, Middle Aged, Obesity genetics, Obesity immunology, Obesity metabolism, Adipose Tissue immunology, Adipose Tissue metabolism, Bariatric Surgery adverse effects, Inflammation immunology, Inflammation metabolism, Signal Transduction
Abstract

Background: Bariatric surgery is associated to improvements in obesity-associated comorbidities thought to be mediated by a decrease of adipose inflammation. However, the molecular mechanisms behind these beneficial effects are poorly understood., Methodology/principal Findings: We analyzed RNA-seq expression profiles in adipose tissue from 22 obese women before and 3 months after surgery. Of 15,972 detected genes, 1214 were differentially expressed after surgery at a 5% false discovery rate. Upregulated genes were mostly involved in the basal cellular machinery. Downregulated genes were enriched in metabolic functions of adipose tissue. At baseline, 26 modules of coexpressed genes were identified. The four most stable modules reflected the innate and adaptive immune responses of adipose tissue. A first module reflecting a non-specific signature of innate immune cells, mainly macrophages, was highly conserved after surgery with the exception of DUSP2 and CD300C. A second module reflected the adaptive immune response elicited by T lymphocytes; after surgery, a disconnection was observed between genes involved in T-cell signaling and mediators of the signal transduction such as CXCR1, CXCR2, GPR97, CCR7 and IL7R. A third module reflected neutrophil-mediated inflammation; after surgery, several genes were dissociated from the module, including S100A8, S100A12, CD300E, VNN2, TUBB1 and FAM65B. We also identified a dense network of 19 genes involved in the interferon-signaling pathway which was strongly preserved after surgery, with the exception of DDX60, an antiviral factor involved in RIG-I-mediated interferon signaling. A similar loss of connection was observed in lean mice compared to their obese counterparts., Conclusions/significance: These results suggest that improvements of the inflammatory state following surgery might be explained by a disruption of immuno-inflammatory cascades involving a few crucial molecules which could serve as potential therapeutic targets.

Published
2015
Full Text
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