Les compétences au cœur de l’évaluation finale de cours

Pour donner suite à une recommandation de la CEEC, le Cégep de Sainte-Foy a créé un atelier destiné aux professeurs qui leur permet de mettre l’accent sur l’aspect synthèse de l’évaluation finale de leur cours. L’atelier a été conçu pour que les professeurs puissent répondre eux-mêmes aux questions touchant l’élaboration d’une telle évaluation, dont le cœur est l’atteinte des compétences du cours

Updated survey of the steroid-converting enzymes in human adipose tissues

Over the past decade, adipose tissues have been increasingly known for their endocrine properties, that is, their ability to secrete a number of adipocytokines that may exert local and/or systemic effects. In addition to these hormonal peptides, adipose tissues have long been recognized as significant sites for steroid hormone transformation and action. We hereby provide an updated survey of the many steroid-converting enzymes that may be detected in human adipose tissues, their activities and potential roles. In addition to the now well-established role of aromatase and 11β-hydroxysteroid dehydrogenase (HSD) type 1, many enzymes have been reported in adipocyte cell lines, isolated mature cells and/or preadipocytes. These include 11βHSD type 2, 17β-HSDs, 3β-HSD, 5α-reductases, sulfatases and glucuronosyltransferases. Some of these enzymes are postulated to bear relevance for adipose tissue physiology and perhaps for the pathophysiology of obesity. This elaborate set of steroid-converting enzymes in the cell types of adipose tissue deserves further scientific attention. Our work on 20α-HSD (AKR1C1), 3αHSD type 3 (AKR1C2) and 17β-HSD type 5 (AKR1C3) allowed us to clarify the relevance of these enzymes for some aspects of adipose tissue function. For example, AKR1C2 expression down-regulation in preadipocytes seems to potentiate the inhibitory action of dihydrotestosterone on adipogenesis in this model. Many additional studies are warranted to assess the impact of intra-adipose steroid hormone conversions on adipose tissue functions and chronic conditions such as obesity, diabetes and cancer

Human visceral and subcutaneous adipocyte isolation and dedifferentiation

Mature adipocytes have been recently shown to reverse their phenotype into fibroblast-like cells in vitro through a technique called ceiling culture. Mature adipocytes can also be isolated from fresh adipose tissue for depot-specific characterization of their function and metabolic properties. Here, we describe a well-established protocol to isolate mature adipocytes from adipose tissues using collagenase digestion, and subsequent steps to perform ceiling cultures. Briefly, adipose tissues are incubated in a Krebs-Ringer-Henseleit buffer containing collagenase to disrupt tissue matrix. Floating mature adipocytes are collected on the top surface of the buffer. Mature cells are plated in a T25-flask completely filled with media and incubated up-side down for a week. An alternative 6-well plate culture approach allows the characterization of adipocytes undergoing dedifferentiation. Adipocyte morphology drastically changes over time of culture. Immunofluorescence can be easily performed on slides cultivated in 6-well plate as demonstrated 65 by FABP4 immunofluorescence staining. FABP4 protein is present in mature adipocytes but down-regulated through dedifferentiation of fat cells. Mature adipocyte dedifferentiation may represent a new avenue for cell therapy and tissue engineering

Adipose tissue attenuation and adipocyte size

Objective: To assess the ability of CT-derived measurements including adipose tissue attenuation and area to predict fat cell hypertrophy and related cardiometabolic risk. Methods: Abdominal adipose tissue areas and radiologic attenuation were assessed using 4 CT images in 241 women (age: 47 years, BMI: 26.5 kg/m2). Fat cell weight was measured in paired VAT and SAT samples. Fasting plasma lipids, glucose and insulin levels were measured. Results: Adipose tissue attenuation was negatively correlated with SAT (r=-0.46) and VAT (r=-0.67) fat cell weight in the corresponding depot (p<0.0001 for both). Women with visceral adipocyte hypertrophy had higher total-, VLDL-, LDL- and HDL-triglyceride and apoB levels as well as a higher cholesterol/HDL-cholesterol ratio, fasting glucose and insulin levels compared to women with smaller visceral adipocytes. Adjustment for VAT area minimized these differences while subsequent adjustment for attenuation eliminated all differences, with the exception of fasting glycaemia. In SAT, adjustment for VAT area and attenuation eliminated all adipocyte hypertrophy-related alterations except for fasting hyperglycaemia. Conclusion: CT-derived adipose tissue attenuation and area both contribute to explain variation in the cardiometabolic risk profile associated with the same biological parameter: visceral fat cell hypertrophy

Abdominal adipocyte populations in women with visceral obesity

Visceral obesity is independently related to numerous cardiometabolic alterations, with adipose tissue dysfunction as a central feature. Objective: To examine whether omental (OM) and subcutaneous (SC) adipocyte size populations in women relate to visceral obesity, cardiometabolic risk factors and adipocyte lipolysis independent of total adiposity. Design and Methods: OM and SC fat samples were obtained during gynecological surgery in 60 women [mean age: 46.1±5.9 years; mean BMI: 27.1±4.5 kg/m2 (range: 20.3-41.1 kg/m2)]. Fresh samples were treated with osmium tetroxide and were analyzed with a Multisizer Coulter. Cell size distributions were computed for each sample with exponential and Gaussian function fits. Results: Computed tomography-measured visceral fat accumulation was the best predictor of larger cell populations as well as the percentage of small cells in both OM and SC fat (p<0.0000 for all). Accordingly, women with visceral obesity had larger cells in the main population and higher proportion of small adipocytes independent of total adiposity (p≤0.05). Using linear regression analysis, we found that women characterized by larger-than-predicted adipocytes in either OM or SC adipose tissue presented higher visceral adipose tissue area, increased percentage of small cells and HOMAir index as well as higher OM adipocyte isoproterenol-, forskolin- and dibutyryl cAMP- stimulated lipolysis compared to women with smaller-than predicted adipocytes, independent of total adiposity (p≤0.05). Conclusion: Excess visceral adipose tissue accumulation is a strong marker of both adipocyte hypertrophy and increased number of small cells in either fat compartment, which relates to higher insulin resistance index and lipolytic response, independent of total adiposity

BPD-DS in the elderly

Background : Biliopancreatic diversion with duodenal switch (BPD-DS) is one of the most effective surgical approaches for the treatment of severe obesity. Objective : The objective of this study is to compare perioperative complications and long-term results of open BPD-DS in elderly versus younger patients. Methods : All patients aged 60 years and above who underwent a primary open BPD-DS in our center were selected (n = 105). Patients were matched 1:1 for sex, BMI, the presence of type 2 diabetes (T2DM), and year of surgery with a group of younger patients (aged ≤55 years). Results : The mean age of the patients was 62.3 ± 2.0 vs. 40.4 ± 7.0 years (p ≤ 0.0001). Initial BMI and prevalence of T2DM were similar in both groups, at 50.9 kg/m2 and 57 %, respectively. Mean operative time (178.6 ± 46.7 vs. 162.5 ± 39.9 min, p = 0.01), hospital stay (10.2 ± 8.3 vs. 6.3 ± 1.5 days, p = 0.0001), and blood loss (593 ± 484 vs. 474 ± 241 ml, p = 0.05) were significantly higher in elderly patients. No difference in 30-day mortality rate was observed (0.9 % in each group). There was no significant difference in major complication rate (16.2 vs. 8.6 %, p = 0.09). At a mean follow-up of 7.1 ± 4.1 years, excess weight loss (67.6 ± 19.2 vs. 72.7 ± 20.7 %, p = 0.06) and BMI (32.2 ± 5.7 vs. 30.8 ± 6.6 kg/m2, p = 0.15) were not significantly different. No significant difference was observed between the two groups for the resolution of T2DM (p = 0.53) and obstructive sleep apnea (p = 0.44). Conclusions : Open BPD-DS is associated with similar long-term benefits in elderly and younger patients, in terms of weight loss and resolution or improvement of obesity-related comorbidities. Perioperative complications might be more frequent in the elderly population, but this was not associated with increased mortality

Molecular remodeling of adipose tissue is associated with metabolic recovery after weight loss surgery

Background Bariatric surgery is an effective therapy for individuals with severe obesity to achieve sustainable weight loss and to reduce comorbidities. Examining the molecular signature of subcutaneous adipose tissue (SAT) following different types of bariatric surgery may help in gaining further insight into their distinct metabolic impact. Results Subjects undergoing biliopancreatic diversion with duodenal switch (BPD-DS) showed a significantly higher percentage of total weight loss than those undergoing gastric bypass or sleeve gastrectomy (RYGB + SG) (41.7 ± 4.6 vs 28.2 ± 6.8%; p = 0.00005). Individuals losing more weight were also significantly more prone to achieve both type 2 diabetes and dyslipidemia remission (OR = 0.75; 95%CI = 0.51–0.91; p = 0.03). Whole transcriptome and methylome profiling showed that bariatric surgery induced a profound molecular remodeling of SAT at 12 months postoperative, mainly through gene down-regulation and hypermethylation. The extent of changes observed was greater following BPD-DS, with 61.1% and 49.8% of up- and down-regulated genes, as well as 85.7% and 70.4% of hyper- and hypomethylated genes being exclusive to this procedure, and mostly associated with a marked decrease of immune and inflammatory responses. Weight loss was strongly associated with genes being simultaneously differentially expressed and methylated in BPD-DS, with the strongest association being observed for GPD1L (r²=0.83; p=1.4x10⁻⁶). Conclusions Present findings point to the greater SAT molecular remodeling following BPD-DS as potentially linked with higher metabolic remission rates. These results will contribute to a better understanding of the metabolic pathways involved in the response to bariatric surgery and will eventually lead to the development of gene targets for the treatment of obesity

Spontaneous neural activity changes after bariatric surgery : a resting-state fMRI study

Background: Metabolic disorders associated with obesity could lead to alterations in brain structure and function. Whether these changes can be reversed after weight loss is unclear. Bariatric surgery provides a unique oppor- tunity to address these questions because it induces marked weight loss and metabolic improvements which in turn may impact the brain in a longitudinal fashion. Previous studies found widespread changes in grey matter (GM) and white matter (WM) after bariatric surgery. However, findings regarding changes in spontaneous neural activity following surgery, as assessed with the fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity of neural activity (ReHo), are scarce and heterogenous. In this study, we used a longitu- dinal design to examine the changes in spontaneous neural activity after bariatric surgery (comparing pre- to post-surgery), and to determine whether these changes are related to cardiometabolic variables. Methods: The study included 57 participants with severe obesity (mean BMI = 43.1 ± 4.3 kg/m 2 ) who under- went sleeve gastrectomy (SG), biliopancreatic diversion with duodenal switch (BPD), or Roux-en-Y gastric bypass (RYGB), scanned prior to bariatric surgery and at follow-up visits of 4 months ( N = 36), 12 months ( N = 29), and 24 months ( N = 14) after surgery. We examined fALFF and ReHo measures across 1022 cortical and subcor- tical regions (based on combined Schaeffer-Xiao parcellations) using a linear mixed effect model. Voxel-based morphometry (VBM) based on T1-weighted images was also used to measure GM density in the same regions. We also used an independent sample from the Human Connectome Project (HCP) to assess regional differences between individuals who had normal-weight ( N = 46) or severe obesity ( N = 46). Results: We found a global increase in the fALFF signal with greater increase within dorsolateral prefrontal cortex, precuneus, inferior temporal gyrus, and visual cortex. This effect was more significant 4 months after surgery. The increase within dorsolateral prefrontal cortex, temporal gyrus, and visual cortex was more limited after 12 months and only present in the visual cortex after 24 months. These increases in neural activity measured by fALFF were also significantly associated with the increase in GM density following surgery. Furthermore, the in- crease in neural activity was significantly related to post-surgery weight loss and improvement in cardiometabolic variables, such as blood pressure. In the independent HCP sample, normal-weight participants had higher global and regional fALFF signals, mainly in dorsolateral/medial frontal cortex, precuneus and middle/inferior temporal gyrus compared to the obese participants. These BMI-related differences in fALFF were associated with the in- crease in fALFF 4 months post-surgery especially in regions involved in control, default mode and dorsal attention networks. Conclusions: Bariatric surgery-induced weight loss and improvement in metabolic factors are associated with widespread global and regional increases in neural activity, as measured by fALFF signal. These findings along- side the higher fALFF signal in normal-weight participants compared to participants with severe obesity in an independent dataset suggest an early recovery in the neural activity signal level after the surgery

Neuroanatomical changes in white and grey matter after sleeve gastrectomy

Background: MRI studies show that obese adults have reduced grey matter (GM) and white matter (WM) tissue density as well as altered WM integrity. Bariatric surgery can lead to substantial weight loss and improvements in metabolic parameters, but it remains to be examined if it induces structural brain changes. The aim of this study was to characterize GM and WM density changes measured with MRI in a longitudinal setting following sleeve gastrectomy, and to determine whether any changes are related to inflammation and cardiometabolic blood markers. Methods: 29 participants with obesity (age: 45.9 ​± ​7.8 years) scheduled to undergo sleeve gastrectomy 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-6, C-reactive protein and lipopolysaccharide-binding protein) were measured at each time point. A linear mixed effect model was used to compare brain changes before and after SG, controlling for age, sex, 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-derived regions of interest, and linear mixed-effect models were used. Results: As 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, postcentral gyrus, cerebellum, hippocampus and insula as well as right fusiform gyrus, right parahippocampal gyrus, right lingual gyrus and right amygdala. 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. A linear mixed-effect model also showed associations between post-operative reductions in lipopolysaccharide-binding protein, 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 individuals who were severely obese with a group of individuals who were lean for age, sex 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). Conclusions: Bariatric 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 participants who were severely obese and those who were normal-weight in a separate dataset, which may suggest a recovery of WM and GM alterations after bariatric surgery