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Obesity and its metabolic complications are characterized by subclinical systemic and tissue inflammation. In rodent models of obesity, inflammation and metabolic impairments are linked with intestinal barrier damage. However, whether intestinal permeability is altered in human obesity remains to be investigated. In a cohort of 122 severely obese and non-obese patients, we analyzed intestinal barrier function combining in vivo and ex vivo investigations. We found tight junction impairments in the jejunal epithelium of obese patients, evidenced by a reduction of occludin and tricellulin. Serum levels of zonulin and LPS binding protein, two markers usually associated with intestinal barrier alterations, were also increased in obese patients. Intestinal permeability per se was assessed in vivo by quantification of urinary lactitol/mannitol (L/M) and measured directly ex vivo on jejunal samples in Ussing chambers. In the fasting condition, L/M ratio and jejunal permeability were not significantly different between obese and non-obese patients, but high jejunal permeability to small molecules (0.4 kDa) was associated with systemic inflammation within the obese cohort. Altogether, these results suggest that intestinal barrier function is subtly compromised in obese patients. We thus tested whether this barrier impairment could be exacerbated by dietary lipids. To this end, we challenged jejunal samples with lipid micelles and showed that a single exposure increased permeability to macromolecules (4 kDa). Jejunal permeability after the lipid load was two-fold higher in obese patients compared to non-obese controls and correlated with systemic and intestinal inflammation. Moreover, lipid-induced permeability was an explicative variable of type 2 diabetes. In conclusion, intestinal barrier defects are present in human severe obesity and exacerbated by a lipid challenge. This paves the way to the development of novel therapeutic approaches to modulate intestinal barrier function or personalize nutrition therapy to decrease lipid-induced jejunal leakage in metabolic diseases. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Objective: Heat shock protein 60 (Hsp60) is an adipokine, and its serum concentrations are higher in patients with obesity compared to lean patients. This study aimed to analyze the effect of bariatric surgery on circulating concentrations of Hsp60 in morbid obesity and their correlation with inflammation and metabolic and cardiovascular risk., Methods: Fifty-three females with morbid obesity undergoing bariatric surgery were enrolled. Serum parameters and anthropometric measures were obtained at baseline and 3 to 12 months post surgery., Results: During the 12-month observation period, Hsp60 decreased significantly from 31.6 ± 4.7 ng/mL at baseline to 22.3 ± 3.0 ng/mL (3 months), 26.5 ± 5.5 (6 months), and 21.1 ± 3.3 ng/mL (12 months). Preoperatively, Hsp60 concentrations correlated positively with total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B (ApoB) and negatively with adiponectin. At the end of the observation period, serum Hsp60 positively correlated with triglycerides, ApoB, HbA 1c , and C-reactive protein (CRP). Patients in the highest quartile of serum Hsp60 were characterized by significantly elevated CRP and interleukin 6 independently of BMI, glycemia, and insulinemia. At baseline and 12 months after surgery, Hsp60 positively correlated with the ApoB/ApoA1 ratio and the cholesterol/high-density lipoprotein cholesterol ratio., Conclusions: Hsp60 concentrations are elevated in morbid obesity and decreased after surgery-induced weight loss. Their correlation with inflammatory markers and cardiovascular risk might link obesity and cardiovascular disease., (© 2017 The Obesity Society.)

Adipose tissue contains a variety of immune cells, which vary in abundance and phenotype with obesity. The contribution of immune cell-derived factors to inflammatory, fibrotic and metabolic alterations in adipose tissue is not well established in human obesity. Human primary adipose tissue cells, including pre-adipocytes, endothelial cells and mature adipocytes, were used to investigate deregulation of cell- and pathway-specific gene profiles. Among factors known to alter adipose tissue biology, we focus on inflammatory (IL-1β and IL-17) and pro-fibrotic (TGF-β1) factors. rIL-1β and rIL-17 induced concordant pro-inflammatory transcriptional programs in pre-adipocytes and endothelial cells, with a markedly more potent effect of IL-1β than IL-17. None of these cytokines had significant effect on fibrogenesis-related gene expression, contrasting with rTGF-β1-induced up-regulation of extracellular matrix components and pro-fibrotic factors. In mature adipocytes, all three factors promoted down-regulation of genes functionally involved in lipid storage and release. IL-1β and IL-17 impacted adipocyte metabolic genes in relation with their respective pro-inflammatory capacity, while the effect of TGF-β1 occurred in face of an anti-inflammatory signature. These data revealed that IL-1β and IL-17 had virtually no effect on pro-fibrotic alterations but promote inflammation and metabolic dysfunction in human adipose tissue, with a prominent role for IL-1β.

The increasing incidence of obesity and associated metabolic complications is a worldwide public health issue. The role of the gut in the pathophysiology of obesity, with an important part for microbiota, is becoming obvious. In rodent models of diet-induced obesity, the modifications of gut microbiota are associated with an alteration of the intestinal permeability increasing the passage of food or bacterial antigens, which contribute to low-grade inflammation and insulin resistance. In human obesity, intestinal permeability modification, and its role in the crosstalk between gut microbiota changes and inflammation at systemic and tissular levels, are still poorly documented. Hence, further characterization of the triggering mechanisms of such inflammatory responses in obese subjects could enable the development of personalized intervention strategies that will help to reduce the risk of obesity-associated diseases., (© 2016 médecine/sciences – Inserm.)

In obesity, insulin resistance is linked to inflammation in several tissues. Although the gut is a very large lymphoid tissue, inflammation in the absorptive small intestine, the jejunum, where insulin regulates lipid and sugar absorption is unknown. We analyzed jejunal samples of 185 obese subjects stratified in three metabolic groups: without comorbidity, suffering from obesity-related comorbidity, and diabetic, versus 33 lean controls. Obesity increased both mucosa surface due to lower cell apoptosis and innate and adaptive immune cell populations. The preferential CD8αβ T cell location in epithelium over lamina propria appears a hallmark of obesity. Cytokine secretion by T cells from obese, but not lean, subjects blunted insulin signaling in enterocytes relevant to apical GLUT2 mislocation. Statistical links between T cell densities and BMI, NAFLD, or lipid metabolism suggest tissue crosstalk. Obesity triggers T-cell-mediated inflammation and enterocyte insulin resistance in the jejunum with potential broader systemic implications., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Accumulation of visceral adipose tissue correlates with elevated inflammation and increased risk of metabolic diseases. However, little is known about the molecular mechanisms that control its pathological expansion. Transcription factor interferon regulatory factor 5 (IRF5) has been implicated in polarizing macrophages towards an inflammatory phenotype. Here we demonstrate that mice lacking Irf5, when placed on a high-fat diet, show no difference in the growth of their epididymal white adipose tissue (epiWAT) but they show expansion of their subcutaneous white adipose tissue, as compared to wild-type (WT) mice on the same diet. EpiWAT from Irf5-deficient mice is marked by accumulation of alternatively activated macrophages, higher collagen deposition that restricts adipocyte size, and enhanced insulin sensitivity compared to epiWAT from WT mice. In obese individuals, IRF5 expression is negatively associated with insulin sensitivity and collagen deposition in visceral adipose tissue. Genome-wide analysis of gene expression in adipose tissue macrophages highlights the transforming growth factor β1 (TGFB1) gene itself as a direct target of IRF5-mediated inhibition. This study uncovers a new function for IRF5 in controlling the relative mass of different adipose tissue depots and thus insulin sensitivity in obesity, and it suggests that inhibition of IRF5 may promote a healthy metabolic state during this condition.

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.

Proinflammatory cytokines are critically involved in the alteration of adipose tissue biology leading to deterioration of glucose homeostasis in obesity. Here we show a pronounced proinflammatory signature of adipose tissue macrophages in type 2 diabetic obese patients, mainly driven by increased NLRP3-dependent interleukin (IL)-1β production. IL-1β release increased with glycemic deterioration and decreased after gastric bypass surgery. A specific enrichment of IL-17- and IL-22-producing CD4(+) T cells was found in adipose tissue of type 2 diabetic obese patients. Coculture experiments identified the effect of macrophage-derived IL-1β to promote IL-22 and IL-17 production by human adipose tissue CD4(+) T cells. Reciprocally, adipose tissue macrophages express IL-17 and IL-22 receptors, making them sensitive to IL-17 and IL-22. IL-22 increased IL-1β release by inducing pro-IL-1β transcription through activation of C-Jun pathways in macrophages. In sum, these human data identified IL-1β and the T-cell cytokine IL-22 as key players of a paracrine inflammatory pathway previously unidentified in adipose tissue, with a pathological relevance to obesity-induced type 2 diabetes. These results provide an additional rationale for targeting IL-1β in obesity-linked type 2 diabetes and may have important implications for the conception of novel combined anti-IL-1β and anti-IL-22 immunotherapy in human obesity., (© 2014 by the American Diabetes Association.)

Aims and Hypothesis: Mast cells are immune cells known for their role in several inflammatory and fibrotic diseases. Recent works in mice suggest that mast cells could be cellular actors involved in the pathophysiology of obesity, a disease characterized by white adipose tissue (WAT) and systemic inflammation. The aim of the study was to better characterize mast cells in WAT of obese with or without type 2 diabetes and lean subjects as well as to explore the relationship with WAT inflammation and fibrosis., Methods: Subcutaneous and omental adipose tissue from six lean subjects, 10 obese nondiabetic, and 10 diabetic patients was analyzed by immunohistochemistry and real-time PCR for inflammatory and fibrosis markers. Cytokines secretion of mast cells isolated from WAT and cultured in different conditions was estimated by cytokine array kit., Results: We found that mast cells are activated in human adipose tissue and localized preferentially in fibrosis depots, a local condition that stimulates their inflammatory state. Mast cells with tryptase(+) chymase(+) staining tended to be higher in obese omental adipose tissue. We found positive links between mast cell number and several characteristics of obese WAT including fibrosis, macrophage accumulation, and endothelial cell inflammation. Mast cell number and their inflammatory phenotype are associated with diabetes parameters., Conclusion and Interpretation: Mast cells are cellular actors of WAT inflammation and possibly fibrotic state found in obesity and diabetes. Whether mast cells could be involved in the pathophysiology of diabetes needs additional study as well as the positioning of these cells in driving pathological alterations of WAT in these chronic metabolic diseases.

Background: Obesity is characterized by chronic low-grade inflammation that may lead to emotional distress and behavioural symptoms. This study assessed the relationship between adiposity, low-grade inflammation, eating behaviour and emotional status in obese women awaiting gastric surgery and investigated the effects of surgery-induced weight loss on this relationship., Method: A total of 101 women with severe or morbid obesity awaiting gastric surgery were recruited. Assessments were performed before and at 1 year post-surgery and included the measurement of neuroticism and extraversion using the revised Neuroticism-Extraversion-Openness personality inventory (NEO-PI-R) and eating behaviour using the Three-Factor Eating Questionnaire (TFEQ). Blood samples were collected for the measurement of serum inflammatory markers [interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP)] and adipokines (leptin, adiponectin)., Results: At baseline, body mass index (BMI) was positively correlated with inflammatory markers and adipokines. Regression analyses adjusting for age and diabetes revealed that baseline concentrations of IL-6 and hsCRP were associated with the depression and anxiety facets of neuroticism, with higher inflammation predicting higher anxiety and depression. This association remained significant after adjusting for BMI. Gastric surgery induced significant weight loss, which correlated with reduced inflammation. After controlling for BMI variations, decreases in inflammatory markers, notably hsCRP, were associated with reduced anxiety and TFEQ-cognitive restraint scores., Conclusions: These findings indicate strong associations between adiposity, inflammation and affectivity in obese subjects and show that surgery-induced weight loss is associated concomitantly with reduced inflammation and adipokines and with significant improvement in emotional status and eating behaviour. Inflammatory status appears to represent an important mediator of emotional distress and psychological characteristics of obese individuals.

Objective: To investigate the effect of massive weight loss on (1) knee pain and disability, (2) low-grade inflammation and metabolic status and (3) joint biomarkers in obese patients with knee osteoarthritis (OA)., Methods: 140 patients involved in a gastric surgery programme were screened for painful knee OA, and 44 were included (age 44 ± 10.3 years, body mass index (BMI) 50.7 ± 7.2 kg/m(2)). Clinical data and biological samples were collected before and 6 months after surgery., Results: Before surgery, interleukin 6 (IL-6) levels were correlated with levels of high-sensitivity C reactive protein (hsCRP) (p=0.006) and Helix-II (p=0.01), a biomarker of cartilage turnover, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score (p=0.03). Surgery resulted in substantial decrease in BMI (-20%). Levels of insulin and insulin resistance were decreased at 6 months. Knee pain decreased after surgery (24.5 ± 21 mm vs 50 ± 26.6 mm; p<0.001), and scores on all WOMAC subscales were improved. Levels of IL-6 (p<0.0001), hsCRP (p<0.0001), orosomucoid (p<0.0001) and fibrinogen (p=0.04) were decreased after surgery. Weight loss resulted in a significant increase in N-terminal propeptide of type IIA collagen levels (+32%; p=0.002), a biomarker of cartilage synthesis, and a significant decrease in cartilage oligomeric matrix protein (COMP) (-36%; p<0.001), a biomarker of cartilage degradation. Changes in COMP concentration were correlated with changes in insulin levels (p=0.02) and insulin resistance (p=0.05)., Conclusion: Massive weight loss improves pain and function and decreases low-grade inflammation. Change in levels of joint biomarkers with weight loss suggests a structural effect on cartilage.

Objective: At present, circulating markers characterizing the inflammatory infiltration of white adipose tissue (WAT) in human obesity are not well known. We previously identified, by a pangenomic approach (microarrays), the urokinase plasminogen activator receptor (PLAUR or CD87) as a potential marker of subcutaneous adipose tissue macrophage infiltration (ATM)., Method: We studied i) the presence of PLAUR protein in WAT; ii) the PLAUR amount in plasma of obese patients; iii) the circulating variations during surgery-induced weight loss, and iv) the correlations between PLAUR circulating levels and bioclinical parameters., Results: We observed that PLAUR is preferentially expressed by infiltrating ATMs, with a typical localization on macrophage membrane. Circulating soluble PLAUR levels were significantly elevated in obese patients compared to lean controls. However, despite a trend towards a decrease 3 months after weight loss, PLAUR plasma levels were not modulated during a 1-year weight loss follow-up, suggesting the contribution of secretion sites other than subcutaneous WAT in obese patients., Conclusions: These findings indicate that PLAUR mRNA expression could be used for the estimation of local subcutaneous ATMs infiltration in obese patients, but it cannot be used as a systemic marker of this inflammatory infiltration in dynamic phases of weight loss., (Copyright © 2011 S. Karger AG, Basel.)

Objective: Obesity alters gut microbiota ecology and associates with low-grade inflammation in humans. Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of morbid obesity resulting in drastic weight loss and improvement of metabolic and inflammatory status. We analyzed the impact of RYGB on the modifications of gut microbiota and examined links with adaptations associated with this procedure., Research Design and Methods: Gut microbiota was profiled from fecal samples by real-time quantitative PCR in 13 lean control subjects and in 30 obese individuals (with seven type 2 diabetics) explored before (M0), 3 months (M3), and 6 months (M6) after RYGB., Results: Four major findings are highlighted: 1) Bacteroides/Prevotella group was lower in obese subjects than in control subjects at M0 and increased at M3. It was negatively correlated with corpulence, but the correlation depended highly on caloric intake; 2) Escherichia coli species increased at M3 and inversely correlated with fat mass and leptin levels independently of changes in food intake; 3) lactic acid bacteria including Lactobacillus/Leuconostoc/Pediococcus group and Bifidobacterium genus decreased at M3; and 4) Faecalibacterium prausnitzii species was lower in subjects with diabetes and associated negatively with inflammatory markers at M0 and throughout the follow-up after surgery independently of changes in food intake., Conclusions: These results suggest that components of the dominant gut microbiota rapidly adapt in a starvation-like situation induced by RYGB while the F. prausnitzii species is directly linked to the reduction in low-grade inflammation state in obesity and diabetes independently of calorie intake.

Objective: Adipocytes secrete a series of acute phase proteins including serum amyloid A (SAA); the link with metabolic status is unknown. We studied the variations of expression of the SAA gene in adipose and liver tissues and of SAA serum levels, as well as their relationships with metabolic features during weight loss., Research Methods and Procedures: Plasmatic variations of SAA, inflammatory markers (high sensitivity C-reactive protein, interleukin-6, fibrinogen, and orosomucoid), and adipokines (adiponectin, leptin) were studied in 60 morbidly obese patients before and after gastric surgery. For 10 subjects, SAA mRNA expression was measured at baseline in subcutaneous white adipose tissue (scWAT) and visceral white adipose tissue (vWAT) and in the liver. The evolution of SAA mRNA expression was also studied after surgery in scWAT., Results: SAA serum concentration displayed a significant reduction 3 months after surgery and remained stable beyond 6 months. mRNA expression of inducible SAA isoforms (SAA 1 and 2) in scWAT was higher than in vWAT (p = 0.01) and the liver (p < 0.01) and correlated significantly with BMI, SAA, and high sensitivity C-reactive protein serum concentrations but not with metabolic markers (glucose, insulin, lipid parameters, adiponectin). SAA serum level and its variation during weight loss significantly correlated with adiposity markers (BMI and adipocyte volume, p < 0.01) and inflammatory markers but not with variations of metabolic parameters. The variations of SAA expression in scWAT after surgery correlated with changes in BMI and SAA protein serum levels (p < 0.05)., Discussion: SAA can be considered as a marker of adiposity-induced low-grade inflammation but not of the metabolic status of obese subjects.

Abstract: Caloric restriction still remains the most efficient way to promote weight loss. Deciphering the molecular basis of adaptation to energy restriction is critical for the tailoring of new therapeutic strategies. This review focuses on the recent input of gene profiling on adipose tissue in obesity pathogenesis and on the new insights on adaptations occurring during very low caloric diet (VLCD) in humans. Hypocaloric diets improve a wide range of metabolic parameters including lipolytic efficiency, insulin sensitivity, and inflammatory profile. In the subcutaneous white adipose tissue (scWAT) the VLCD induced a decrease in the mRNA levels for the antilipolytic α2-adrenergic receptor associated with changes in catecholamine-induced adipocyte lipolytic capacity. The improvement in insulin sensitivity was not associated with a change in subcutaneous adipose tissue adiponectin gene expression or in its plasma level, suggesting that adiponectin is not involved in the regulation of VLCD-induced improvement of insulin sensitivity and that there is a small contribution of subcutaneous adipose tissue to plasma adiponectin levels. Pangenomic microarray studies in human scWAT revealed that a panel of inflammatory markers and acute phase reactants were over expressed in obese compared to lean subjects. Caloric restriction improved the inflammatory profile of obese subjects through a decrease of pro-inflammatory factors and an increase of anti-inflammatory molecules. These genes were mostly expressed in the stroma vascular fraction of the adipose tissue. Specific cell-type isolation and immunohistochemistry demonstrated that monocyte/macrophage lineage cells were responsible for the expression of both mRNA and protein inflammatory markers. The acute phase proteins serum amyloid A was highly expressed in mature adipocytes from obese subjects. Caloric restriction decreased both serum amyloid mRNA and circulating levels. Obesity now clearly appears as chronic low-grade inflammation state. Modulation of the inflammatory pathways may represent new therapeutic targets for the treatment of obesity-related complications. [Copyright &y& Elsevier]

Introduction: L’obésité et les syndromes métaboliques sont associés à un état d’inflammation bas-grade auquel les monocytes circulants participent. Ceux-ci sont classés en trois sous-populations aux propriétés différentes : monocytes classiques CD14 + CD16 − (MC), intermédiaires CD14 + CD16 + (MI) et non classiques CD14dimCD16 + + (MNC). Notre équipe a montré que le nombre de MI et MNC augmente dans l’obésité et varie avec la perte de poids (Poitou et al 2011). Nous caractérisons ici le profil phénotypique des 3 sous-populations monocytaires dans les mêmes conditions. Patients et méthodes: Les 3 sous-populations ont été triées par Cytométrie en Flux chez 7 sujets obèses (OB) avant et 3 mois après bypass gastrique, 6 sujets obèses et diabétiques (OB/D) et 7 sujets non obèses (C). L’expression génique de 20 gènes impliqués dans les fonctions monocytaires (migration, adhésion, phagocytose, production de cytokines) a été analysée par Low Density Array. Résultats: Les gènes CX3CR1, CSF1R (récepteurs de la fractalkine et du Colony Stimulating Factor 1), SELPLG (selectin P ligand) et TNF sont fortement exprimés par les MNC et MI comparativement aux MC quelque soit le groupe OB ou C. Leur expression est augmentée dans le groupe OB et diminue avec la perte de poids. Les MI expriment fortement CCR5 tandis que CCR2 est majoritaire dans les MC. L’expression de ces deux récepteurs de surface est augmentée dans le groupe OB et diminue avec la perte de poids. Le statut diabétique ne modifie pas l’expression des gènes dans les 3 sous populations sauf pour PPARG, plus exprimé par les MNC et MC du groupe OB/D. Conclusion: L’expression de gènes impliqués dans la migration et l’adhésion monocytaire est augmentée dans les 3 sous populations monocytaires chez les sujets obèses et diminue avec la perte de poids suggérant que les monocytes des sujets obèses ont des capacités migratoires dans les tissus différentes. [Copyright &y& Elsevier]

Introduction: L’obésité est considérée comme un état inflammatoire chronique de bas-grade qui varie au cours de variations pondérales. Cependant les mécanismes impliqués dans les modulations inflammatoires observées après perte de poids restent peu connus. Notre étude a analysé les variations sériques d’un large panel de cytokines en relation avec les variations des phénotypes biocliniques après bypass gastrique (BPG). Patients et méthodes: Dans une cohorte de 14 femmes témoins (IMC 21.5±0,3kg/m2), 33 femmes obèses (IMC 48.2±1,3kg/m2), 18 femmes obèses et diabétiques (IMC 52.8±2,0kg/m2), nous avons évalué simultanément les concentrations sériques de 27 cytokines par dosage multiplex avant et 3, 6 et 12 mois après BPG. Résultats: Les concentrations de 10 facteurs détectés sont augmentées chez le sujet obèse (Eotaxine, IL-10, IL-1RA, IL-8, IL-9, IP-10, MCP1, MIP1β, VEGF, RANTES) comparé aux sujets témoins. L’eotaxine est en plus augmentée chez les diabétiques. Au cours de la perte de poids, les concentrations d’IL10, MIP1, MCP1, IL8, EOTAXIN, RANTES et VEGF, suivent un profil de variation bi-phasique: après une diminution à 3 mois, les concentrations atteignent le niveau pré-chirurgical à 6 mois et se stabilisent à 12 mois. L’évolution de l’apport calorique présente un profil similaire alors que la corpulence, la masse grasse, le statut métabolique et la CRPus s’améliorent de manière continue au cours du temps. A 12 mois, les variations de cytokines ne sont pas différentes entre les deux groupes de patients « bons répondeurs » (- 34,7% de perte de poids) ou « mauvais répondeurs » (- 19,3%). Conclusion: Nos résultats indiquent qu’un large panel de cytokines circulantes contribue à l’inflammation systémique chez le sujet obèse et suggèrent pour certaines d’entre elles une relation avec les changements alimentaires sans lien avec l’amélioration de la masse grasse ou le statut métabolique. [Copyright &y& Elsevier]

Introduction: Le tissu adipeux (TA) des sujets obèses est caractérisé par une infiltration macrophagique et une modification du profil d’expression génique et sécrétoire des adipocytes. Précédemment, notre équipe a montré que la protéine de l’inflammation Sérum Amyloid A (SAA) est produite par l’adipocyte dans le TA des sujets obèses. Son rôle n’est cependant pas défini. Notre hypothèse est que la SAA adipocytaire puisse être liée aux caractéristiques pathologiques du TA chez le sujet obèse. Patients et méthodes: Nous avons étudié chez 37 sujets obèses (BMI=49,3±1,5kg/m2), l’expression génique et protéique des SAAs au sein des 3 territoires du TA : sous cutané sus-fascial, s/c sous-fascial et omental. Nous avons analysé les relations avec le pourcentage de macrophages et avec les gènes co-exprimés afin d’identifier des classes fonctionnelles de gènes co-régulés avec la SAA. Résultats: Le pourcentage d’adipocytes exprimant la SAA est supérieur dans le TA s/c sus-fascial (11±1, vs 8±1 et 6±1) à celui des TA s/c sous-fascial et omental. Dans les trois territoires, il est significativement corrélé à la taille adipocytaire. Dans le TA sous cutané sus-fascial, ce pourcentage est évalué à 2,4 % pour les adipocytes dont la taille est inférieure à 60μm et à 9,4 % pour les adipocytes hypertrophiques (>90μm). Il est également corrélé avec le % de macrophages (R=0,5, p=9.10−.4). L’analyse transcriptomique par puces à cDNA a montré que le gène ABCA1, transporteur cellulaire impliqué dans l’efflux de cholestérol, est co-exprimé avec le gène SAA. Dans un sous-groupe de 20 sujets, il existe une corrélation entre l’expression protéique d’ABCA1 et de SAA (R=0,7, p=3.10−.4). Conclusion: Ce travail suggère une action localisée de la SAA dans le TA sous cutané sus facial, notamment dans les adipocytes hypertrophiques, et plus particulièrement un rôle dans l’efflux de cholestérol adipocytaire. [Copyright &y& Elsevier]