Biology subjects

Marceau, S.

Publications and source records attributed to Marceau, S..

3 recordsLinked to original sources

bioRxiv2022

Increased adipose tissue indices of androgen catabolism and aromatization in women with metabolic dysfunction

BackgroundBody fat distribution is a risk factor for obesity-associated comorbidities, and adipose tissue dysfunction plays a role in this association. In humans, there is a sex difference in body fat distribution, and steroid hormones are known to regulate several cellular processes within adipose tissue. Our aim was to investigate if intra-adipose steroid concentration and expression or activity of steroidogenic enzymes were associated with features of adipose tissue dysfunction in individuals with severe obesity. MethodsSamples from 40 bariatric candidates (31 women, 9 men) were included in the study. Visceral (VAT) and subcutaneous adipose tissue (SAT) were collected during surgery. Adipose tissue morphology was measured by a combination of histological staining and semi-automated quantification. Following extraction, intra-adipose and plasma steroid concentrations were determined by liquid chromatography, electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Aromatase activity was estimated using product-over-substrate ratio, while AKR1C2 activity was measured directly by fluorogenic probe. Gene expression was measured by quantitative PCR. ResultsVAT aromatase activity was positively associated with VAT adipocyte hypertrophy (p-valueadj < 0.01) and negatively with plasma HDL-cholesterol (p-valueadj < 0.01), while SAT aromatase activity predicted dyslipidemia in women even after adjustment for waist circumference, age and hormonal contraceptive use. We additionally compared women with high and low visceral adiposity index (VAI) and found that VAT excess is characterized by adipose tissue dysfunction, increased androgen catabolism mirrored by increased AKR1C2 activity and higher aromatase expression and activity indices. ConclusionIn women, increased androgen catabolism or aromatization is associated with visceral adiposity and adipose tissue dysfunction. DISCLOSURE SUMMARYAT obtained consulting fees form Bausch Health, Novo Nordisk and research funding from Johnson & Johnson Medical Companies as well as Medtronic and GI Windows for studies unrelated to this manuscript. The other authors have nothing to disclose.

physiology↗

bioRxiv2019

Neuroanatomical Changes in White and Grey Matter after Sleeve Gastrectomy

BackgroundMRI studies show that obese adults have reduced grey (GM) and white matter (WM) tissue density as well as altered WM integrity. It remains to be examined if bariatric surgery induces structural brain changes. The aim of this study is to characterize GM and WM density changes in a longitudinal setting, comparing pre- and post-operation and to determine whether these changes are related to inflammation and cardiometabolic markers.\n\nMethods29 severely obese participants (age: 45.9{+/-}7.8 years) scheduled to undergo sleeve gastrectomy (SG) were recruited. High-resolution T1-weighted anatomical images were acquired 1 month prior to as well as 4 and 12 months after surgery. GM and WM densities were quantified using voxel-based morphometry (VBM). Circulating lipid profile, glucose, insulin and inflammatory markers (interleukin (IL)-6, C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) were measured at each time point. A linear mixed effect model was used to compare brain changes before and after SG, controlling for age, gender, initial BMI and diabetic status. To assess the associations between changes in adiposity, metabolism and inflammation and changes in GM or WM density, the mean GM and WM densities were extracted across all the participants using atlas, and linear mixed-effect models were used.\n\nResultsAs expected, weight, BMI, waist circumference and neck circumference significantly decreased after SG compared with baseline (p<0.001 for all). A widespread increase in WM density was observed after surgery, particularly in the cerebellum, brain stem, cerebellar peduncle, cingulum, corpus callosum and corona radiata (p<0.05, after FDR correction). Significant increases in GM density were observed 4 months after SG compared to baseline in several brain regions such as the bilateral occipital cortex, temporal cortex, precentral gyrus and cerebellum as well as right fusiform gyrus, right hippocampus and right insula. These GM and WM increases were more pronounced and widespread after 12 months and were significantly associated with post-operative weight loss and the improvement of metabolic alterations. Our linear mixed-effect models also showed strong associations between post-operative reductions in LBP, a marker of inflammation, and increased WM density. To confirm our results, we tested whether the peak of each significant region showed BMI-related differences in an independent dataset (Human Connectome Project). We matched a group of severely obese individuals with a group of lean individuals for age, gender and ethnicity. Severe obesity was associated with reduced WM density in the brain stem and cerebellar peduncle as well as reduced GM density in cerebellum, regions that significantly changed after surgery (p<0.01 for all clusters).\n\nConclusionsBariatric surgery-induced weight loss and improvement in metabolic alterations is associated with widespread increases in WM and GM densities. These post-operative changes overlapped with baseline brain differences between severely obese and normal-weight individuals, which may suggest a recovery of WM and GM alterations after bariatric surgery.

neuroscience↗

bioRxiv2018

Epigenetic transmission of cardiometabolic risk in offspring discordant for maternal gestational metabolic fitness

OBJECTIVEDiabesity during gestation predisposes offspring to lifetime cardiometabolic risk. We demonstrated that maternal biliopancreatic diversion surgery (BPD) improved metabolic fitness and pregnancies reducing cardiometabolic risk in siblings born after (AMS) compared to before maternal surgery (BMS). We found differential methylation of inflammatory and glucoregulatory genes in peripheral blood cell DNA in offspring and in mothers after BPD compared to preoperative \"control\" women. Here we study offspring trajectories of cardiometabolic risk markers and determine persistence of the methylome related to body weight (BMI) and gestational weight gain (GWG).\n\nRESEARCH DESIGN AND METHODSProspective, cross-sectional study of 133 mothers with 89 BMS and 183 AMS offspring born mean 4 years after BPD and 83 unoperated control women was conducted, and differential methylation patterns in mothers were compared with those of offspring during 2-26 years.\n\nRESULTSIndependent of maternal or offspring BMI and GWG, postoperative maternal metabolic fitness was associated with improved cardiometabolic phenotype in AMS vs. BMS offspring sustained beyond puberty. BMS offspring exhibited increasing linear trajectories of weight, cardiometabolic and inflammation risk factors versus normative horizontal trajectories of AMS offspring. Methylation differences between AMS and BMS offspring identified 45 625 differentially methylated sites, 73% overlapping with those of mothers vs. controls; 4 446 demonstrated similar sustained directionality of differences in methylation levels; 154 sites exhibited significant correlation coefficients (r[≥]0.4) overrepresented within genes associated with cardiometabolic risk, growth and inflammation.\n\nCONCLUSIONMaternal BPD appears to epigenetically prevent transmission of cardiometabolic risk independent of BMI.

developmental biology↗