Chronic intermittent hypoxia triggers cardiac fibrosis: Role of epididymal white adipose tissue senescent remodeling?

AIM: Obstructive sleep apnea (OSA) is a growing health problem affecting nearly 1 billion people worldwide. The landmark feature of OSA is chronic intermittent hypoxia (CIH), accounting for multiple organ damage, including heart disease. CIH profoundly alters both visceral white adipose tissue (WAT) and heart structure and function, but little is known regarding inter-organ interaction in the context of CIH. We recently showed that visceral WAT senescence drives myocardial alterations in aged mice without CIH. Here, we aimed at investigating whether CIH induces a premature visceral WAT senescent phenotype, triggering subsequent cardiac remodeling. METHODS: In a first experiment, 10-week-old C57bl6J male mice (n = 10/group) were exposed to 14 days of CIH (8 h daily, 5%-21% cyclic inspired oxygen fraction, 60 s per cycle). In a second series, mice were submitted to either epididymal WAT surgical lipectomy or sham surgery before CIH exposure. Finally, we used p53 deficient mice or Wild-type (WT) littermates, also exposed to the same CIH protocol. Epididymal WAT was assessed for fibrosis, DNA damages, oxidative stress, markers of senescence (p16, p21, and p53), and inflammation by RT-qPCR and histology, and myocardium was assessed for fibrosis and cardiomyocyte hypertrophy. RESULTS: CIH-induced epididymal WAT remodeling characterized by increased fibrosis, oxidative stress, DNA damage response, inflammation, and increased expression of senescent markers. CIH-induced epididymal WAT remodeling was associated with subtle and early myocardial interstitial fibrosis. Both epididymal WAT surgical lipectomy and p53 deletion prevented CIH-induced myocardial fibrosis. CONCLUSION: Short-term exposure to CIH induces epididymal WAT senescent remodeling and cardiac interstitial fibrosis, the latter being prevented by lipectomy. This finding strongly suggests visceral WAT senescence as a new target to mitigate OSA-related cardiac disorders.

French National Authority for Health assessment of metabolic surgery for type 2 diabetes remission-A meta-analysis in patients with class I to III obesity.

OBJECTIVE: Randomized controlled trials (RCTs) have demonstrated the superiority of metabolic surgery (MS) over medical therapy (MT) in patients with obesity and type 2 diabetes, leading, to a joint statement in 2016 proposing MS to patients with class I obesity and uncontrolled glycemia. Yet, these RCTs included few patients with class I obesity (body mass index 30-35 kg/m2) and even fewer patients with overweight. Our aim was to provide an updated systematic review (SR) with meta-analysis (MA) of RCTs reporting diabetes remission (DR) after MS in these patients. RESEARCH DESIGN AND METHODS: We included in the SR with MA only RCTs with at least 24-month follow-up found in Medline, Cochrane Library, Embase, and LiSSA between January 2008 and September 2022 comparing DR post-MT versus post-MS. We calculated relative risk (RR) and 95 % confidence intervals (CIs) using the Mantel-Haenszel random-effects approach to examine differences in DR between patients allocated to MS versus MT. RESULTS: DR was significantly higher in MS versus MT after 36 months' follow-up in patients with obesity (RR = 6.65 [95 %CI 2.24;19.79]; I² = 27 %; 5 trials, 404 patients), but also specifically in patients with class I obesity (RR = 5.27 [1.31;21.23]; I² = 0 %; 4 trials, 80 patients). Furthermore, and in line with previous results, all additional MAs performed in patients with obesity in this work favor MS (specifically Roux-en-Y gastric bypass) over MT at 24, 36 (only) and 60 months of follow-up. CONCLUSIONS: Although the data available in patients with class I obesity and type 2 diabetes remains limited, MA shows higher rates of DR after MS compared with MT after 36 months' follow-up in these patients. Consequently, the French National Authority for Health French (HAS) recommends MS for these patients.

Osteoarthritis in patients with obesity: The bariatric surgery impacts on its evolution.

Obesity is one of the main modifiable risk factors for osteoarthritis (OA). Moreover, obesity is associated with greater pain intensity and functional limitation, but also with a significantly lower responder rate to intra-articular treatments. Consequently, an arthroplasty is indicated earlier and more frequently in patients with obesity. However, pain and functional symptoms improve slightly less after arthroplasty in patients with obesity, who display higher incidence of early and late complications following prosthetic surgery. Bariatric surgery (BS) has increased worldwide and is efficient to induce major and sustainable weight-loss. Importantly, BS significantly reduces pain and functional limitation in patients with symptomatic knee OA. Biomarkers analysis also revealed a decrease in catabolic factors and an increase in anabolic one after BS suggesting a structural protective effect in knee OA. Nevertheless, the impact of BS prior to arthroplasty remains unclear. BS seems to decrease short- and mid-term complications such as infections or thrombosis. However, BS does not appear to modify long-term complications rate, and may even increase it, especially revisions and infections. Although few studies have compared the symptomatic and functional outcomes of joint replacement with or without BS, these are not significantly improved by prior BS. Despite these heterogeneous results, medico-economic studies found that BS prior to arthroplasty was cost-effective. To conclude, BS could significantly reduce the symptoms of OA and potentially slow its progression, but appears more disappointing in preventing long-term complications of arthroplasties and improving their functional results.

Management of Severe Malnutrition Post-bariatric Surgery Using Artificial Nutrition.

BACKGROUND: Bariatric surgery (BS) results in major and sustained weight loss and improves comorbidities in patients with obesity but can also lead to malnutrition, especially through severe malabsorption and/or surgical complications. Little is known about the efficacy of artificial nutrition (AN) in this setting. METHODS: In this case series, we describe data from consecutive severely malnourished patients after BS (resectional and non-resectional), managed by AN at our hospital unit over a 4-year period. RESULTS: Between January 2018 and June 2022, 18 patients (mean ± SD age 42.2 ± 10.4 years, 94% women) required AN following BS complications. At the time of AN initiation, more than half of the patients (53%) had multiple revisional surgeries (up to four). Mean BMI was 49.7 ± 11.3 kg/m2 before BS and 29.6 ± 9.6 kg/m2 when AN was initiated. Most patients (n=16, 90%) received enteral nutrition. AN management resulted in weight regain (+4.7kg ± 8.0, p=0.034), increased serum albumin (+28%, p=0.02), pre-albumin (+88%, p=0.002), and handgrip strength (+38%, p=0.078). No major AN complication nor death was observed. Median total AN duration was 4.5 months [1-12]. During follow-up, the cumulative duration of hospitalization was 33 days [4-88] with a median of 2.5 hospitalizations [1-8] per patient. CONCLUSION: Malnutrition can occur after any BS procedure, and AN when required in this setting appears safe and effective on nutritional parameters. It is important to recognize the potential risk factors for malnutrition, which include excessive weight loss resulting from surgical complications, eating disorders, multiple revisional BS, and pregnancy.

Revisional Roux-en-Y Gastric Bypass After Sleeve Gastrectomy for Gastro-esophageal Reflux Disease and or Insufficient Weight-Loss: a Comparative Study.

INTRODUCTION: Sleeve gastrectomy (SG) is a popular surgical weight-loss procedure, but there are increasing reports of revisional Roux-Y-gastric-bypass (R-RYGB) to manage weight-loss failure (WLF) or proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) after SG, with little data available in these settings. METHODS: This retrospective study included all consecutive patients undergoing R-RYGB for WLF or RGERD after SG in two bariatric care centers from 2012 to 2018. RESULTS: Of 720 patients, 46 (3.6%) underwent R-RYGB (RGERD, n = 25; 54.4%; WLF, n = 21; 45.6%) within 44.8 ± 27.5 months post-SG. SG had enabled 27% ± 11.6 total weight loss (TWL) in the RGERD group vs. 7.2% ± 12.5% TWL in the WLF group (p < 0.001). At R-RYGB, WLF-group patients had a higher BMI (47.8 ± 8.4 vs. 34.7 ± 6.1 kg/m2; p < 0.001) and a higher number of comorbidities (2.4 ± 1.5 vs 1.5 ± 1.2; p < 0.02) compared to RGERD-group patients, while severe morbidity (Clavien-Dindo ≥ IIIb) was not significantly different between groups (6.5% vs 2.1%, p = 0.6). %TWL was still higher in the RGERD group at 12 months post-R-RYGB (35.6% ± 10.4 vs. 23.8% ± 9.2; p < 0.01) but not after 24 months post-R-RYGB. R-RYGB corrected reflux symptoms in 32 (94%) patients and reduced PPI use in 29 (97%) patients (p < 0.001), with no significant between-group difference. A history of adjustable gastric banding (AGB) (N = 8;17.4%) prior to SG was associated with a similar prevalence of GERD at R-RYGB and a lower %TWL (AGB:13.1 ± 10.2 vs. No AGB:31.6 ± 8.5; p < 0.05) at 3 years post-R-RYGB. CONCLUSION: R-RYGB following SG provides remission of reflux symptoms in 94% of patients and extra weight loss in patients with WLF, except in patients with a history of AGB prior to SG.

Precision Bariatric/Metabolic Medicine and Surgery.

Indications and techniques of bariatric surgery (BS) have constantly evolved in recent decades and now face new challenges [...].

Follow-Up, Safety, and Satisfaction with Tele-bariatric Follow-Up Implemented During the COVID-19 French Lockdown: a 2-Year Follow-Up Study.

BACKGROUND: The COVID-19 pandemic was initially responsible for a global restricted access to healthcare resources including the follow-up of at-risk populations such as bariatric patients. We substituted face-to-face bariatric follow-up outpatient clinics (FTFC) with teleclinics (TC) during the lockdown. MATERIAL AND METHODS: We retrospectively reviewed data collected on all patients scheduled for TC during the French lockdown period (March 15 to May 15, 2020) (N = 87). Our aims were to present the patients' outcomes at one and 2 years post-TC implementation and describe patient/practitioner satisfaction. RESULTS: Seven (8%) patients required FTFC, and 80 (92%) underwent TC (study population) for preoperative bariatric assessment (N = 3) and postoperative follow-up (N = 77) after 23.6 ± 29 months following surgery. TC was performed with video and audio (N = 46; 57.5%) or audio alone when video was impossible (N = 34; 42.5%). Sixteen (20%) patients presented at least one complication identified at the first TC and were managed accordingly. There were no readmissions at 30/90 days post-TC. At 1-year after the first TC, overall follow-up rate was 94.9% (TC: 73% vs FTFC: 27%). Patients surveyed on the main advantages of TC over FTFC (N = 46) cited: saving time (97.8%) at a mean 3.9 ± 6.4 h saved per TC, work-advantages (94.3%), and comparable relevance of TC (84.8%). At 2 years post-TC implementation, follow-up rate was 93.5% and satisfaction rate was 80%, with 33% of patients preferring to return to FTFC. CONCLUSIONS: TC is a satisfactory substitute for FTFC, enabling continued bariatric follow-up during and beyond the pandemic setting without compromising patient safety. However, the modest satisfaction outcomes at 2 years highlight a need to discuss follow-up preferences in order to achieve optimal outcomes.

Effect of exercise training after bariatric surgery: A 5-year follow-up study of a randomized controlled trial.

BACKGROUND AND OBJECTIVES: We previously showed in a 6-month randomized controlled trial that resistance training and protein supplementation after bariatric surgery (Roux-en-Y gastric bypass, RYGB) improved muscle strength without significant effect on weight loss and body composition changes. We performed a 5-year follow-up study in these subjects with the aim 1) to assess the long-term effect of this exercise training intervention and 2) to analyze associations between habitual physical activity (PA) and weight regain at 5 years. METHODS: Fifty-four out of 76 initial participants (follow-up rate of 71%) completed the 5-year follow-up examination (controls, n = 17; protein supplementation, n = 22; protein supplementation and resistance training, n = 15). We measured body weight and composition (DXA), lower-limb strength (leg-press one-repetition maximum) and habitual PA (Actigraph accelerometers and self-report). Weight regain at 5 years was considered low when <10% of 12-month weight loss. RESULTS: Mean (SD) time elapse since RYGB was 5.7 (0.9) y. At 5 years, weight loss was 32.8 (10.1) kg, with a mean weight regain of 5.4 (SD 5.9) kg compared with the 12-month assessment. Moderate-to-vigorous PA (MVPA) assessed by accelerometry did not change significantly compared with pre-surgery values (+5.2 [SD 21.7] min/d, P = 0.059), and only 4 (8.2%) patients reported participation in resistance training. Muscle strength decreased over time (overall mean [SD]: -49.9 [53.5] kg, respectively, P<0.001), with no statistically significant difference between exercise training intervention groups. An interquartile increase in MVPA levels was positively associated with lower weight regain (OR [95% CI]: 3.27 [1.41;9.86]). CONCLUSIONS: Early postoperative participation in a resistance training protocol after bariatric surgery was not associated with improved muscle strength after 5 years of follow-up; however, increasing physical activity of at least moderate intensity may promote weight maintenance after surgery. PA may therefore play an important role in the long-term management of patients with obesity after undergoing bariatric procedure.

Effect of COVID-19 Lockdowns on Physical Activity, Eating Behavior, Body Weight and Psychological Outcomes in a Post-Bariatric Cohort.

PURPOSE: Little is known about the consequences of COVID-19 lockdowns on physical activity (PA), eating behavior, and mental health in post-bariatric surgery (BS) patients. We aimed to analyze the relations between changes in PA during COVID-19 lockdowns and changes in body weight and a comprehensive set of lifestyle and psychological outcomes in patients who have undergone BS. MATERIAL AND METHODS: In April-May 2020 (lockdown#1), we performed an online survey in a cohort of 937 adults who underwent BS and were followed-up at our university medical center for at least one year. We assessed changes in PA, eating behavior, body weight, fatigue, and depression (PHQ-9). In November-December 2020 (lockdown#2), we recorded body weight in 280 patients who had reported decreased PA during lockdown #1. RESULTS: During lockdown #1 (N = 420 patients included, 44% response rate), decreased PA was reported by 67% patients. Compared to those who reported increased or unchanged PA, patients with decreased PA were more likely to report a ≥ 5% weight gain (OR (95% CI): 3.15 (1.46-7.65), increased fatigue (2.08 (1.36-3.23)), a worsening of eating behavior (2.29 (1.47-3.58)), and moderate-to-severe depressive symptoms (4.74 (2.14-11.76)). During lockdown #2 (N = 225 patients, 80% response rate), significant weight gain since before lockdown #1 was reported (+ 2.8 (95% CI: 1.7-3.8) kg, p < 0.001), with 36% patients reporting a ≥ 5% weight gain. CONCLUSIONS: PA may counteract detrimental effects of COVID-19 lockdown on post-BS weight trajectories and mental health outcomes. Follow-up measures are needed in this setting to assess the long-term impact of lockdown.

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

Roux-en-Y gastric bypass (RYGB) is efficient at inducing drastic albeit variable weight loss and type-2 diabetes (T2D) improvements in patients with severe obesity and T2D. We hypothesized a causal implication of the gut microbiota (GM) in these metabolic benefits, as RYGB is known to deeply impact its composition. In a cohort of 100 patients with baseline T2D who underwent RYGB and were followed for 5-years, we used a hierarchical clustering approach to stratify subjects based on the severity of their T2D (Severe vs Mild) throughout the follow-up. We identified via nanopore-based GM sequencing that the more severe cases of unresolved T2D were associated with a major increase of the class Bacteroidia, including 12 species comprising Phocaeicola dorei, Bacteroides fragilis, and Bacteroides caecimuris. A key observation is that patients who underwent major metabolic improvements do not harbor this enrichment in Bacteroidia, as those who presented mild cases of T2D at all times. In a separate group of 36 patients with similar baseline clinical characteristics and preoperative GM sequencing, we showed that this increase in Bacteroidia was already present at baseline in the most severe cases of T2D. To explore the causal relationship linking this enrichment in Bacteroidia and metabolic alterations, we selected 13 patients across T2D severity clusters at 5-years and performed fecal matter transplants in mice. Our results show that 14 weeks after the transplantations, mice colonized with the GM of Severe donors have impaired glucose tolerance and insulin sensitivity as compared to Mild-recipients, all in the absence of any difference in body weight and composition. GM sequencing of the recipient animals revealed that the hallmark T2D-severity associated bacterial features were transferred and were associated with the animals' metabolic alterations. Therefore, our results further establish the GM as a key contributor to long-term glucose metabolism improvements (or lack thereof) after RYGB.

[new recommandation for medical and surgical care of obesity]. / Chirurgie bariatrique : vers de nouvelles recommandations.

BARIATRIC SURGERY: TOWARDS NEW RECOMMANDATIONS The french NICE has produced a document describing the current limits to the optimal care of obesity, in particular concerning bariatric surgery. This document also states the perspectives and work that needs to be undergone to improve obesity care. Since october 2020, a working group appointed by the French NICE is writing the clinical recommandations for obesity care in 2nd and 3rd care referral, addressing both the medical and surgical care of obesity. This work has known some delay mainly due to the several waves of COVID-19.

CHIRURGIE BARIATRIQUE: VERS DE NOUVELLES RECOMMANDATIONS La Haute Autorité de santé (HAS) s'est autosaisie pour produire une note de cadrage « Parcours obésité ¼ rappelant les limites actuelles de la prise en charge de cette maladie et établir une liste de propositions et de travaux à conduire pour l'améliorer. L'un d'entre eux est la production de recommandations de « prise en charge de l'obésité de l'adulte dans les 2e et 3e recours de soin ¼, travail en cours depuis octobre 2020, mais retardé par la pandémie de Covid-19. Ces recommandations concerneront la prise en charge non seulement médicale mais aussi chirurgicale de l'obésité.

Microbiome and metabolome features of the cardiometabolic disease spectrum.

Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages-acute coronary syndrome, chronic IHD and IHD with heart failure-and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.

Persistence of severe liver fibrosis despite substantial weight loss with bariatric surgery.

BACKGROUND AND AIMS: It remains unclear to what extent and which components of advanced liver disease improve after bariatric surgery. We herein describe the histological outcome in patients with advanced NASH and its relationship with weight loss and metabolic improvement. APPROACH AND RESULTS: One hundred ninety-six patients with advanced NASH underwent bariatric surgery, 66 of whom agreed to a follow-up liver biopsy at 6 ± 3 years (36 with advanced fibrosis [AF] and 30 with high activity [HA] grade without AF). Liver biopsies LBs were centrally read and histological response was defined as the disappearance of AF or HA. Bariatric surgery induced major histological improvement: 29% of patients had normal histology at follow-up biopsy; 74% had NASH resolution without fibrosis progression; and 70% had ≥1 stage fibrosis regression. However, AF persisted in 47% of patients despite NASH resolution and some degree of fibrosis reversal, only evidenced by the EPoS seven-tier staging classification. These patients had lower weight loss and reduced hypertension or diabetes remission rates. Older age and sleeve gastrectomy were the only independent predictors for persistent AF after adjustment for duration of follow-up. All HA patients had major histological improvement: 50% normal histology, 80% NASH resolution, and 86% a ≥1 grade steatosis reduction. Patients with normal liver at follow-up had the largest weight loss and metabolic improvement. Independent predictors of normal liver were amount of weight loss, high histological activity, and the absence of AF before surgery. CONCLUSIONS: Although bariatric surgery successfully reverses active steatohepatitis, AF can persist for many years and is associated with lesser weight loss and metabolic improvement. Weight loss alone may not be sufficient to reverse AF.

Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism.

OBJECTIVES: Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome's functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation. DESIGN: We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice. RESULTS: Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration. CONCLUSION: Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity. TRIAL REGISTRATION NUMBER: NCT02059538.

Fibrogenesis Marker PRO-C3 Is Higher in Advanced Liver Fibrosis and Improves in Patients Undergoing Bariatric Surgery.

CONTEXT: Serum propeptides of type III and type VI collagen (PRO-C3 and PRO-C6) are elevated in advanced nonalcoholic fatty liver disease (NAFLD), but their value in patients with severe obesity and their evolution after bariatric surgery (BS) is unknown. It is unclear if these markers of fibrogenesis are affected by adipose tissue fibrosis (ATF). OBJECTIVE: We studied the association of PRO-C3 and PRO-C6 with liver fibrosis before BS, examined their evolution after BS, and evaluated how much patients' ATF contribute to their levels. METHODS: Serum PRO-C3 and PRO-C6 were measured in 158 BS patients and compared with liver, subcutaneous, and omental adipose tissue histology obtained during surgery. PRO-C3 and PRO-C6 levels of 63 patients were determined in follow-up at 3 and 12 months post-BS. RESULTS: Patients in the highest quartile of PRO-C3 had a higher risk of advanced liver fibrosis (stage F3-4; odds ratio 5.8; 95% CI [1.5-29.9]; P = 0.017) vs the lowest quartile (adjustment for age, gender, and BMI). PRO-C3 was positively correlated with markers of insulin resistance and liver enzymes. After BS, PRO-C3 levels decreased in patients with high baseline liver fibrosis. This decrease correlated with improvement of metabolic and liver parameters. PRO-C6 was not related to stage of liver fibrosis. ATF did not correlate with PRO-C3 or PRO-C6 levels at baseline or after BS. CONCLUSION: PRO-C3 was associated with advanced liver fibrosis in patients with severe obesity, and decreased after BS, without being affected by ATF. These data suggest that BS prominently eliminates drivers of hepatic fibrogenesis in NAFLD.

Adipose tissue fibrosis assessed by high resolution ex vivo MRI as a hallmark of tissue alteration in morbid obesity.

To determine whether magnetic resonance imaging (MRI) when used in an optimal ex vivo setting can help detecting and quantifying the 3D fibrosis fraction in human subcutaneous adipose tissue (SAT) samples, as compared to histology. This prospective observational study was approved by our institutional review board 3D MRI acquisitions were performed at 4.0 T (Bruker) on XX human SAT samples (around 1 cm3) collected from biopsy in morbidly obese patients. Such acquisitions included saturation-recovery T1 mapping (spatial resolution: 200 µm, acquisition time: ~16 minutes) and DIXON imaging (spatial resolution: 200 µm, acquisition time: ~20 minutes). After MRI, histological quantification of fibrosis was performed using picrosirius staining. T1 maps were clustered based on a k-means algorithm allowing quantification of fibrosis within the adipose tissue and percentage of fibrosis over the entire sample volume was calculated. Fat maps were computed from DIXON in-phase and out-of-phase images. The 3D MRI fibrosis percentage within the SAT samples were comprised between 6% and 15%. Excellent correlations and levels of agreement were observed between single slice MRI and histology (r=0.9, P=0.08) and between 3D MRI and histology in terms fibrosis percentages within SAT samples (r=0.9, P=0.01). High Field ex vivo MRI was able to quantify fibrosis in human SAT samples with high agreement with histology and moreover to provide 3D SAT fibrosis quantification avoiding histological sampling errors.

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

OBJECTIVE: To evaluate the effect on anthropometric, metabolic and adipose tissue parameters of switching ART-controlled persons living with HIV (PLWH) from a protease inhibitor regimen to raltegravir/maraviroc. DESIGN: Sub-study of the ANRS157 ROCnRAL study with the investigation of subcutaneous abdominal adipose tissue (SCAT) biopsy at inclusion and study end. METHODS: We performed lipoaspiration of paired SCAT samples, histology on fresh/fixed samples and examined the transcriptomic profile analyzed using Illumina microarrays after RNA extraction. Statistical analyses used the Wilcoxon-paired test. RESULTS: The patients (n = 8) were mainly male (7/8), aged (mean ±â€Šstandard error of the mean) 54.9 ±â€Š1.2 years, BMI 26.1 ±â€Š1.2 kg/m2, CD4+ 699 ±â€Š56 cells/mm3, all viral load (VL) <50 copies/ml. After a follow-up of 6 ±â€Š0.5 months, all PLWH remained with VL <50 copies/ml. BMI, trunk and limb fat amounts were unchanged yet systemic insulin resistance increased. Adipose tissue histology was unchanged except for borderline increased adipocyte diameter (P = 0.1). Among the 16 094 RNA transcripts, 458 genes were up-regulated and 244 were down-regulated. Analyses of the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases, evaluating modifications in the main functional pathways, revealed that genes related to immune recognition/function were less expressed as were genes encoding T-cell receptor and receptor signaling pathways. The gene expression profiles indicated decreased inflammation but genes involved in adipogenesis and insulin resistance were overexpressed. CONCLUSION: After 6 months of raltegravir/maraviroc, adipogenesis-related gene profile was enhanced in SCAT, in agreement with a tendency for increased adipocyte size. Enhanced SCAT insulin resistance-related profile was concordant with higher systemic insulin resistance. However, the immune activation/inflammation profile was globally lowered. We propose that raltegravir/maraviroc might favor SCAT gain but reduce inflammation/immune activation.

Resting-state connectivity within the brain's reward system predicts weight loss and correlates with leptin.

Weight gain is often associated with the pleasure of eating food rich in calories. This idea is based on the findings that people with obesity showed increased neural activity in the reward and motivation systems of the brain in response to food cues. Such correlations, however, overlook the possibility that obesity may be associated with a metabolic state that impacts the functioning of reward and motivation systems, which in turn could be linked to reactivity to food and eating behaviour and weight gain. In a study involving 44 female participants [14 patients with obesity, aged 20-63 years (mean: 42, SEM: 3.2 years), and 30 matched lean controls, aged 22-60 years (mean: 37, SEM: 1.8 years)], we investigated how ventromedial prefrontal cortex seed-to-voxel resting-state connectivity distinguished between lean and obese participants at baseline. We used the results of this first step of our analyses to examine whether changes in ventromedial prefrontal cortex resting-state connectivity over 8 months could formally predict weight gain or loss. It is important to note that participants with obesity underwent bariatric surgery at the beginning of our investigation period. We found that ventromedial prefrontal cortex-ventral striatum resting-state connectivity and ventromedial-dorsolateral prefrontal cortex resting-state connectivity were sensitive to obesity at baseline. However, only the ventromedial prefrontal cortex-ventral striatum resting-state connectivity predicted weight changes over time using cross-validation, out-of-sample prediction analysis. Such an out-of-sample prediction analysis uses the data of all participants of a training set to predict the actually observed data in one independent participant in the hold-out validation sample and is then repeated for all participants. In seeking to explain the reason why ventromedial pre-frontal cortex-ventral striatum resting-state connectivity as the central hub of the brain's reward and motivational system may predict weight change over time, we linked weight loss surgery-induced changes in ventromedial prefrontal cortex-ventral striatum resting-state connectivity to surgery-induced changes in homeostatic hormone regulation. More specifically, we focussed on changes in fasting state systemic leptin, a homeostatic hormone signalling satiety, and inhibiting reward-related dopamine signalling. We found that the surgery-induced increase in ventromedial prefrontal cortex-ventral striatum resting-state connectivity was correlated with a decrease in fasting-state systemic leptin. These findings establish the first link between individual differences in brain connectivity in reward circuits in a more tonic state at rest, weight change over time and homeostatic hormone regulation.

COVID-19 and its Severity in Bariatric Surgery-Operated Patients.

OBJECTIVE: Obesity is a major risk factor for severe forms of coronavirus disease (COVID-19), but little is known about the post-bariatric surgery (BS) setting. The prevalence of likely COVID-19 and its risk factors in patients followed up after BS was assessed. METHODS: A total of 738 patients who underwent BS and were followed up at a university medical center were surveyed. A retrospective comparison of characteristics at baseline, 1 year after BS, and at the time of lockdown was performed between patients with COVID-19-likely events (CL) based on a combination of reported symptoms and those for whom COVID-19 was unlikely. RESULTS: CL occurred in 62 (8.4%) patients, among whom 4 (6.4%) had a severe form requiring hospitalization and 1 (1.6%) died. The CL group had a higher proportion of persistent type 2 diabetes (T2D) at last follow-up (36.2% vs. 20.3%, P = 0.01). BMI at the time of lockdown was lower in the CL group (30.2 ± 5.1 vs. 32.8 ± 6.5 kg/m2 ; P < 0.01) with higher percent weight loss since BS in the CL group. Severe forms of COVID-19 requiring hospitalization were associated with persistent T2D at the last follow-up visit. CONCLUSIONS: In BS patients, CL were associated with persistent T2D and lower BMI.