Sérum Amyloid A (un nouveau marqueur du tissu adipeux)

L obésité et ses complications sont caractérisées par une dysfonction d un organe clé le tissu adipeux. Le but ce travail était d identifier des biomarqueurs du tissu adipeux pouvant être impliqués dans la physiopathologie de l obésité et de ses complications. L étude du profil transcriptionnel dans le tissu adipeux dans une situation d obésité extrême par mutation génétique du gène de la leptine et dans un autre modèle de restriction calorique, ont permis d identifier la protéine SAA comme un nouveau biomarqueur exprimé dans le tissu adipeux. Nous avons montré que la SAA est produite chez le patient massivement obèse par l adipocyte et participe à l élévation de la concentration plasmatique. La SAA est un marqueur d adiposité (augmentation de la masse grasse totale et d hypertrophie adipocytaire). L augmentation de la SAA au niveau du tissu adipeux est liée à une augmentation de l inflammation au sein de ce tissu et en particulier à l infiltration macrophagique. D autres mécanismes pourraient également être en jeu tels que l augmentation systémique des cytokines proinflammatoires (TNF , IL6, IL1 ), l hypoxie, le métabolisme des glucocorticoïdes. L expression et la production de la SAA par l adipocyte diminuent avec la perte de poids induite par une restriction calorique parallèlement à une diminution de l inflammation du tissu adipeux (diminution du nombre de macrophages et modification génique du profil inflammatoire). Des résultats préliminaires nous laissent supposer que la SAA adipocytaire pourrait être impliquée dans le métabolisme du cholestérol dans l adipocyte et dans l infiltration macrophagique. Sur le plan systémique, la SAA circulante n est pas un marqueur d insulinorésistance chez le sujet massivement obèse mais est augmentée dans le syndrome d apnées du sommeil. Les propriétés décrites de la SAA dans la dysfonction des HDL et l athérosclérose nous laissent supposer que la SAA pourrait faire le lien entre obésité, syndrome d apnées du sommeil et athérosclérose.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Obésités hypothalamiques chez l'adulte (aspects nutritionnels et comorbidités)

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

Taille adipocytaire et phénotypes métaboliques avant et après bypass gastrique

Introduction : L hypertrophie adipocytaire est responsable de perturbations métaboliques qui tendent à s améliorer après perte de poids. Nous posons l hypothèse que la taille adipocytaire est associée à l apparition et à la sévérité des complications métaboliques au cours de l obésité massive ainsi qu à leur amélioration voire leur disparition après la chirurgie bariatrique. Objectif : rechercher des liens entre le volume adipocytaire et les phénotypes métaboliques dans une cohorte de patients obèses morbides et en cinétique au cours d une perte de poids induite par bypass gastrique. Population étudiée : 358 patients obèses morbides (BMI moyen à 47,4 pour les femmes, 48,7 pour les hommes) inclus pour l étude des données en préopératoire (281 femmes dont 86 diabétiques et 77 hommes dont 38 diabétiques). 107 femmes de cette cohorte (dont 36 diabétiques) ont été étudiées à 3 mois, 6 mois et 12 mois en post opératoire. Résultats : le volume adipocytaire est associé, en pré opératoire, au statut diabétique chez la femme, indépendamment de l âge, de l IMC ou du pourcentage de masse grasse androïde mais également au statut glycémique indépendamment de l âge et de l IMC. Un volume adipocytaire élevé en préopératoire est associé à une meilleure amélioration de la glycémie en post opératoire. Au cours du temps, après la chirurgie, il existe un lien entre l évolution du volume adipocytaire et les marqueurs du métabolisme glucidique. En revanche nous n avons pas trouvé de lien entre le volume adipocytaire en pré opératoire et la résolution du diabète, ni entre la variation du volume adipocytaire entre T0 et T3 mois et la résolution du diabète à 12 moisIntroduction : The adipocyte hypertrophy is responsible for metabolic disturbances that tend to improve after weight loss. We hypothesize that adipocyte size is associated with the onset and severity of metabolic complications of massive obesity and their improvement even their disappearance after bariatric surgery. Objective: To look for links between adipocyte volume and metabolic phenotypes in a cohort of morbidly obese patients and in kinetic during a weight loss induced by gastric bypass. Study population: 358 morbidly obese patients (mean BMI 47.4 for women, 48.7 for men) included in the study data preoperatively (281 women, 86 diabetic and 77 men including 38 diabetics). 107 women in this cohort (including 36 diabetic) were studied at 3 months, 6 months and 12 months after surgery. Results: The adipocyte volume is associated, preoperatively, to the diabetic status in women, regardless of age, BMI or percentage of body fat but also to the glycemic status regardless of age and the BMI. A high preoperative adipocyte volume is associated with a greater improvement in glycemia after surgery. Over time, after surgery, there is a link between changes in adipocyte volume and markers of glucose metabolism. However we did not find a link between adipocyte volume preoperatively and resolution of diabetes, nor between adipocyte volume change between T0 and T3 month and resolution of diabetes at 12 monthsST QUENTIN EN YVELINES-BU (782972101) / SudocSudocFranceF

Prevalence and severity of malnutrition in hospitalized COVID-19 patients

International audienceBackground & aims: Nutritional knowledge in patients with SARS-Cov2 infection (COVID-19) is limited. Our objectives were: i) to assess malnutrition in hospitalized COVID-19 patients, ii) to investigate the links between malnutrition and disease severity at admission, iii) to study the impact of malnutrition on clinical outcomes such as transfer to an intensive care unit (ICU) or death.Methods: Consecutive patients hospitalized in a medicine ward at a university hospital were included from March 21st to April 24th 2020 (n = 114, 60.5% males, age: 59.9 ± 15.9 years). Nutritional status was defined using Global Leadership Initiative on Malnutrition (GLIM) criteria. Clinical, radiological and biological characteristics of COVID-19 patients were compared according to the presence of malnutrition. Logistic regression was used to assess associations between nutritional parameters and unfavourable outcomes such as transfer to intensive care unit (ICU) or death.Results: The overall prevalence of malnutrition was 42.1% (moderate: 23.7%, severe: 18.4%). The prevalence of malnutrition reached 66.7% in patients admitted from ICU. No significant association was found between nutritional status and clinical signs of COVID-19. Lower albumin levels were associated with a higher risk of transfer to ICU (for 10 g/l of albumin, OR [95%CI]: 0.31 [0.1; 0.7]; p < 0.01) and this association was independent of age and CRP levels.Conclusions: COVID-19 in medical units dedicated to non-intensive care is associated with a high prevalence of malnutrition, especially for patients transferred from ICU. These data emphasize the importance of early nutritional screening in these patients to adapt management accordingly

Clinical management of patients with genetic obesity during COVID-19 pandemic: position paper of the ESE Growth & Genetic Obesity COVID-19 Study Group and Rare Endo-ERN main thematic group on Growth and Obesity

International audienceThis article aims to provide guidance on prevention and treatment of COVID-19 in patients with genetic obesity. Key principals of the management of patients with genetic obesity during COVID-19 pandemic for patients that have contracted COVID-19 are to be aware of: possible adrenal insufficiency (e.g., POMC deficiency, PWS); a more severe course in patients with concomitant immunodeficiency (e.g., LEP and LEPR deficiency), although defective leptin signalling could also be protective against the pro-inflammatory phenotype of COVID-19; disease severity being masked by insufficient awareness of symptoms in syndromic obesity patients with intellectual deficit (in particular PWS); to adjust medication dose to increased body size, preferably use dosing in m2; the high risk of malnutrition in patients with Sars-Cov2 infection, even in case of obesity. Key principals of the obesity management during the pandemic are to strive for optimal obesity management and a healthy lifestyle within the possibilities of the regulations to prevent weight (re)gain and to address anxiety within consultations, since prevalence of anxiety for COVID-19 is underestimated

A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome

Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinitis pigmentosa, obesity, polydactyly, cognitive impairment and renal failure. Pathogenic variants in 24 genes account for the molecular basis of &gt;80% of cases. Toward saturated discovery of the mutational basis of the disorder, we carefully explored our cohorts and identified a hominid-specific SINE-R/VNTR/Alu type F (SVA-F) insertion in exon 13 of BBS1 in eight families. In six families, the repeat insertion was found in trans with c.1169 T &gt; G, p.Met390Arg and in two families the insertion was found in addition to other recessive BBS loci. Whole genome sequencing, de novo assembly and SNP array analysis were performed to characterize the genomic event. This insertion is extremely rare in the general population (found in 8 alleles of 8 BBS cases but not in &gt;10 800 control individuals from gnomAD-SV) and due to a founder effect. Its 2435 bp sequence contains hallmarks of LINE1 mediated retrotransposition. Functional studies with patient-derived cell lines confirmed that the BBS1 SVA-F is deleterious as evidenced by a significant depletion of both mRNA and protein levels. Such findings highlight the importance of dedicated bioinformatics pipelines to identify all types of variation

Statin therapy is associated with lower prevalence of gut microbiota dysbiosis

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n\ua0=\ua0888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n\ua0=\ua02,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics