Micronutrient status 2 years after bariatric surgery: a prospective nutritional assessment.

Background: Among commonly performed bariatric surgeries, biliopancreatic diversion with duodenal switch (BPD-DS) provides greater weight loss than Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG), with sustained metabolic improvements. However, the risk of long-term nutritional deficiencies due to the hypoabsorptive component of BPD-DS hinders its widespread use. Objective: The aim of the study was to examine nutritional status over 2 years after BPD-DS, RYGB or SG. Methods: Patients were recruited in the REMISSION trial (NCT02390973), a single-center, prospective study. Out of 215 patients, 73, 48 and 94, respectively, underwent BPD-DS, RYGB or SG. Weight loss, micronutrient serum levels (including iron, calcium, parathormone, vitamins A, B12 and D), and nutritional supplementation were assessed over 2 years. Patients were supplemented according to the type of surgery and individual micronutrient level evolution. Results: At baseline, BPD-DS patients were younger than SG patients (p = 0.0051) and RYGB patients had lower body mass index (p < 0.001). Groups had similar micronutrient levels before surgery, with vitamin D insufficiency as the most prevalent nutritional problem (SG: 38.3%, RYGB: 39.9%, BPD-DS: 54.8%, p = 0.08). BPD-DS patients showed lower levels of iron, calcium and vitamin A than SG patients at 24 months. Groups had similar levels of vitamin D at 24 months. Prevalence of vitamin D, calcium, iron, vitamin A and vitamin B12 deficiency was similar among groups at 24 months. Rates of vitamin D insufficiency and iron deficiency were lower at 24 months than at baseline. Micronutrient intake was consistent with recommendations in groups post-surgery, but most BPD-DS patients took vitamin A and vitamin D supplement doses above initial recommendations. Conclusion: With appropriate medical and nutritional management, all surgeries led to similar rates of vitamin D, calcium, iron, vitamin A and vitamin B12 deficiencies at 24 months. However, initial vitamin A and vitamin D supplementation recommendations for BPD-DS patients should be revised upwards.

Attitudes and Behaviors towards Food and Weight in Late Pregnancy: A Comparative Approach between Individuals with and without Previous Bariatric Surgery.

The aims of this study were to compare, between pregnant individuals with and without bariatric surgery: (1) eating behaviors, (2) intuitive eating components and, (3) attitudes towards weight gain. This retrospective study included data collected in healthy pregnant individuals with and without previous bariatric surgery who were recruited at the Centre Hospitalier Universitaire (CHU) de Québec-Université Laval. Pregnant individuals who underwent bariatric surgery (biliopancreatic bypass with duodenal switch [n = 14] or sleeve gastrectomy [n = 5]) were individually matched, for age (±0.4 years) and body mass index (BMI) (±0.3 kg/m2), with pregnant individuals who have not received bariatric surgery. In the second trimester, participants completed the Three Factor Eating Questionnaire (TFEQ) and the Intuitive Eating Scale 2 (IES-2). In the third trimester, participants completed the French version of the Pregnancy Weight Gain Attitude Scale assessing attitudes towards weight gain. Pregnant individuals who have had bariatric surgery had a higher score for flexible restraint and a lower score for situational susceptibility to disinhibition compared to individuals who have not had undergone bariatric surgery (2.89 ± 1.15 vs. 1.95 ± 1.31; p = 0.04 and 1.11 ± 1.29 vs. 2.79 ± 1.44, respectively; p < 0.001). Regarding intuitive eating, pregnant individuals who experienced bariatric surgery had a higher score for reliance on internal hunger and satiety cues and a lower one for unconditional permission to eat compared with those who had not experienced bariatric surgery (3.99 ± 0.81 vs. 3.30 ± 1.03; p = 0.02 and 3.28 ± 0.54 vs. 3.61 ± 0.68, respectively; p = 0.03). No difference in attitudes towards weight gain was observed between groups. Overall, pregnant individuals who had undergone bariatric surgery had different eating behaviors and intuitive eating components compared to pregnant individuals without bariatric surgery. These results need to be confirmed in further studies with larger sample sizes.

Trimester-Specific Serum Fructosamine in Association with Abdominal Adiposity, Insulin Resistance, and Inflammation in Healthy Pregnant Individuals.

This study aimed to (1) characterize the variations in serum fructosamine across trimesters and according to pre-pregnancy BMI (ppBMI), and (2) examine associations between fructosamine and adiposity/metabolic markers (ppBMI, first-trimester adiposity, leptin, glucose homeostasis, and inflammation measurements) during pregnancy. Serum fructosamine, albumin, fasting glucose and insulin, leptin, adiponectin, interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations were measured at each trimester. In the first trimester, subcutaneous (SAT) and visceral (VAT) adipose tissue thicknesses were estimated by ultrasound. In the 101 healthy pregnant individuals included (age: 32.2 ± 3.5 y.o.; ppBMI: 25.5 ± 5.5 kg/m2), fructosamine concentrations decreased during pregnancy whereas albumin-corrected fructosamine concentrations increased (p < 0.0001 for both). Notably, fructosamine concentrations were inversely associated with ppBMI, first-trimester SAT, VAT, and leptin (r = −0.55, r = −0.61, r = −0.48, r = −0.47, respectively; p < 0.0001 for all), first-trimester fasting insulin and HOMA-IR (r = −0.46, r = −0.46; p < 0.0001 for both), and first-trimester IL-6 (r = −0.38, p < 0.01). However, once corrected for albumin, most of the correlations lost strength. Once adjusted for ppBMI, fructosamine concentrations were positively associated with third-trimester fasting glucose and CRP (r = 0.24, r = 0.27; p < 0.05 for both). In conclusion, serum fructosamine is inversely associated with adiposity before and during pregnancy, with markers of glucose homeostasis and inflammation, but the latter associations are partially influenced by albumin concentrations and ppBMI.

Impact of weight loss on brain age: Improved brain health following bariatric surgery.

Individuals living with obesity tend to have increased brain age, reflecting poorer brain health likely due to grey and white matter atrophy related to obesity. However, it is unclear if older brain age associated with obesity can be reversed following weight loss and cardiometabolic health improvement. The aim of this study was to assess the impact of weight loss and cardiometabolic improvement following bariatric surgery on brain health, as measured by change in brain age estimated based on voxel-based morphometry (VBM) measurements. We used three distinct datasets to perform this study: 1) CamCAN dataset to train the brain age prediction model, 2) Human Connectome Project (HCP) dataset to investigate whether individuals with obesity have greater brain age than individuals with normal weight, and 3) pre-surgery, as well as 4, 12, and 24 month post-surgery data from participants (n = 87, age: 44.0 ± 9.2 years, BMI: 43.9 ± 4.2 kg/m2) who underwent a bariatric surgery to investigate whether weight loss and cardiometabolic improvement as a result of bariatric surgery lowers the brain age. As expected, our results from the HCP dataset showed a higher brain age for individuals with obesity compared to individuals with normal weight (T-value = 7.08, p-value < 0.0001). We also found significant improvement in brain health, indicated by a decrease of 2.9 and 5.6 years in adjusted delta age at 12 and 24 months following bariatric surgery compared to baseline (p-value < 0.0005 for both). While the overall effect seemed to be driven by a global change across all brain regions and not from a specific region, our exploratory analysis showed lower delta age in certain brain regions (mainly in somatomotor, visual, and ventral attention networks) at 24 months. This reduced age was also associated with post-surgery improvements in BMI, systolic/diastolic blood pressure, and HOMA-IR (T-valueBMI=4.29, T-valueSBP=4.67, T-valueDBP=4.12, T-valueHOMA-IR=3.16, all p-values < 0.05). In conclusion, these results suggest that obesity-related brain health abnormalities (as measured by delta age) might be reversed by bariatric surgery-induced weight loss and widespread improvements in cardiometabolic alterations.

Dietary intakes in pregnant women with previous bariatric surgery.

PURPOSE: To (1) assess dietary intakes of pregnant women with previous bariatric surgery in comparison with Dietary Reference Intakes (DRIs); (2) compare their dietary intakes as well as their diet quality with a control group of pregnant women with no history of bariatric surgery. METHODS: Twenty-eight (28) pregnant women with previous surgery (sleeve gastrectomy, n = 7 and biliopancreatic diversion with duodenal switch, n = 21) were matched for pre-pregnancy body mass index with 28 pregnant women with no history of bariatric surgery. In at least one trimester, participants completed a minimum of 2 Web-based 24-h dietary recalls from which energy, macro- and micronutrient intakes as well as the Canadian Healthy Eating Index (C-HEI) were derived. RESULTS: No differences were observed for energy intake between groups. All women had protein intakes within the recommended range, but most women with previous surgery had carbohydrate (67%) and dietary fiber intakes (98%) below recommendations. In both groups, mean total fat, saturated fatty acids, free sugars and sodium intakes were above recommendations, as opposed to mean vitamin D, folic acid and iron dietary intakes below recommendations for most women. Compared with the control group, pregnant women with previous bariatric surgery had lower overall C-HEI scores. CONCLUSION: These results suggest that pregnant women with previous bariatric surgery would benefit from a nutritional follow-up throughout their pregnancy. LEVEL OF EVIDENCE: III: Evidence obtained from well-designed cohort or case-control analytic studies.

Evaluation of Dietary Assessment Tools Used in Bariatric Population.

Severe obesity is associated with major health issues and bariatric surgery is still the only treatment to offer significant and durable weight loss. Assessment of dietary intakes is an important component of the bariatric surgery process. OBJECTIVE: To document the dietary assessment tools that have been used with patients targeted for bariatric surgery and patients who had bariatric surgery and explore the extent to which these tools have been validated. METHODS: A literature search was conducted to identify studies that used a dietary assessment tool with patients targeted for bariatric surgery or who had bariatric surgery. RESULTS: 108 studies were included. Among all studies included, 27 used a dietary assessment tool that had been validated either as part of the study per se (n = 11) or in a previous study (n = 16). Every tool validated per se in the cited studies was validated among a bariatric population, while none of the tools validated in previous studies were validated in this population. CONCLUSION: Few studies in bariatric populations used a dietary assessment tool that had been validated in this population. Additional studies are needed to develop valid and robust dietary assessment tools to improve the quality of nutritional studies among bariatric patients.

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 opportunity 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 longitudinal 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/m2) who underwent 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 subcortical 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 increase 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 increase 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 alongside 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 â€‹± â€‹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 â€‹< â€‹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 â€‹< â€‹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 â€‹< â€‹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.

Obesity has limited behavioural overlap with addiction and psychiatric phenotypes.

Obesity is a widespread health condition1, likely to be driven by the increased availability of inexpensive high-calorie food2. People vary greatly in their behavioural response to food. Such variation is likely to be driven by behavioural styles3,4, as behaviour accounts for overall food intake5. A prominent hypothesis is that people with obesity respond to rewards similarly to people with addictions such as alcohol abuse or smoking6,7. For instance, perceived overeating or 'uncontrolled eating' (UE) is the most common obesity-associated personality trait8 and resembles the perceived loss of control seen in drug addiction. Likewise, both obesity and addictive behaviours have similar correlations with broad personality domains3. Here we seek to empirically test whether obesity and UE overlap behaviourally with addiction and psychiatric disorders, collectively referred to as phenotypes. We test for behavioural similarity by linking the personality profiles of each phenotype. NEO Personality Inventory profiles of 28 phenotypes were extracted from 22 studies, encompassing summary statistics from 18,611 unique participants. Obesity had moderate and UE high behavioural similarity with addictions. UE also overlapped behaviourally with most psychiatric phenotypes, whereas obesity was behaviourally similar with mood disorders and certain personality disorders. Facet-based phenotype profiles provided more information than domain-based profiles.

Interleukin-1ß and prostaglandin-synthesizing enzymes as modulators of human omental and subcutaneous adipose tissue function.

IL-1ß stimulates expression of prostaglandin (PG)-synthesizing enzymes cyclooxygenase (COX)-2 and aldo-keto reductase (AKR)1B1 in human preadipocytes. We aimed to examine the impact of IL-1ß, COX-2 and AKR1B1 on markers of human visceral and subcutaneous adipose tissue function, and to assess whether PG synthesis by these enzymes mediates IL-1ß effects. Omental and subcutaneous fat samples were obtained from bariatric surgery patients. PG release and expression of inflammatory and adipogenic markers were assessed in explants treated with COX-2 inhibitor NS-398 or AKR1B1 inhibitor Statil, with or without IL-1ß. Preadipocyte differentiation experiments were also performed. IL-1ß decreased expression of PPARγ in both fat depots compared to control and increased expression of NF-κB1, IL-6, CCL-5, ICAM-1 and VEGFA, especially in visceral fat for IL-6, CCL-5 and VEGFA. Adding Statil or NS-398 to IL-1ß blunted PGF2α and PGE2 release, but did not alter IL-1ß effects on adipose tissue function markers. IL-1ß down-regulated adipocyte differentiation whereas NS-398 alone increased this process. However, NS-398 did not prevent IL-1ß inhibition of adipogenesis. We conclude that IL-1ß induces a pro-inflammatory response in human adipose tissues, particularly in visceral fat, and acts independently of concomitant PG release. IL-1ß and COX-2 appear to be critical determinants of adipose tissue pathophysiologic remodeling in obesity.

Biliopancreatic diversion with duodenal switch leads to better postprandial glucose level and beta cell function than sleeve gastrectomy in individuals with type 2 diabetes very early after surgery.

OBJECTIVE: The aim of this study was to compare the short-term effect of sleeve gastrectomy (SG) and biliopancreatic diversion with duodenal switch (DS) in order to determine if exclusion of the upper gastrointestinal tract confers greater metabolic improvement, independent of weight loss. METHODS: Standard meals were administered before and on day 3 and 4 after SG to assess insulin sensitivity, ß-cell function and gastrointestinal hormone responses in matched normoglycemic (NG) and type 2 diabetes (T2D) participants. A third group of matched T2D participants who underwent DS with the same meal test administered prior to and 3days after surgery was also recruited. RESULTS: Despite significant metabolic improvement, T2D participants failed to fully normalize insulin resistance and ß-cell dysfunction 3 and 4days after SG. Our results demonstrate the superiority of DS over SG in terms of short-term improvement in postprandial glucose excursion and ß-cell function 3days after the surgery, with similar improvement in hepatic insulin sensitivity. CONCLUSION: Our findings support the notion that caloric restriction represents an important mechanism to explain the very early anti-diabetic effects observed after bariatric surgery. However, exclusion of the upper gastrointestinal tract also provides further metabolic improvements, possibly mediated by gastrointestinal hormonal responses and altered postprandial glucose absorption.

Impact of Bariatric Surgery on White Adipose Tissue Inflammation.

Excess fat mass accumulation can lead to a wide range of metabolic and cardiovascular complications resulting from dysfunctional adipose tissue (AT). The latter includes immune cell infiltration and altered secretion of anti- and proinflammatory mediators, which contribute to systemic, low-grade inflammation. In this article, we review available literature documenting the impact of surgery-induced weight loss on macrophage infiltration and tissue expression or circulating levels of a broad spectrum of inflammatory mediators. Reports generally show that bariatric surgery may reverse both macrophage infiltration and the altered secretory profile observed in the AT of patients with severe obesity. However, further studies are needed to confirm or elucidate the effects of specific bariatric surgery procedures on white AT inflammation and to shed light on the mechanisms involved in these effects.

Abdominal adipocyte populations in women with visceral obesity.

BACKGROUND: 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.  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<0.0001 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 homeostasis model assessment insulin resistance index as well as higher OM adipocyte isoproterenol-, forskolin- and dbcAMP-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.

Biliopancreatic Diversion with Duodenal Switch in the Elderly: Long-Term Results of a Matched-Control Study.

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/m(2) 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/m(2), 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.

Adipocyte size as a determinant of metabolic disease and adipose tissue dysfunction.

Obesity is a heterogeneous disease and is associated with comorbidities such as type 2 diabetes mellitus, cardiovascular disease and cancer. Several studies have examined the role of dysfunctional adipose tissue in the pathogenesis of obesity, highlighting the contrasting properties and impact of distinct fat compartments, sometimes with contradictory results. Dysfunctional adipose tissue involves enlargement, or hypertrophy, of pre-existing fat cells, which is thought to confer increases in cardiometabolic risk, independent of the level of obesity per se. In this article, we critically analyze available literature that examined the ability of adipocyte cell size to predict metabolic disease and adipose tissue dysfunction in humans. Many studies demonstrate that increased fat cell size is a significant predictor of altered blood lipid profiles and glucose-insulin homeostasis independent of adiposity indices. The contribution of visceral adiposity to these associations appears to be of particular importance. However, available studies are not unanimous and many fat depot-specific aspects of the relationship between increased fat cell size and cardiometabolic risk or parameters of adipose tissue dysfunction are still unresolved. Methodological factors such as the approach used to express the data may represent significant confounders in these studies. Additional studies should consider the fact that the relationship between fat cell size and common adiposity indices is non-linear, particularly when reaching the obese range. In conclusion, our analysis demonstrates that fat cell size is a significant predictor of the cardiometabolic alterations related to obesity. We propose that adipocyte hypertrophy, especially in the visceral fat compartment, may represent a strong marker of limited hyperplasic capacity in subcutaneous adipose tissues, which in turn is associated with the presence of numerous cardiometabolic alterations.

Prostaglandin (PG) F2 alpha synthesis in human subcutaneous and omental adipose tissue: modulation by inflammatory cytokines and role of the human aldose reductase AKR1B1.

INTRODUCTION: PGF2α may be involved in the regulation of adipose tissue function. OBJECTIVES: 1) To examine PGF2α release by primary preadipocytes, mature adipocytes and whole tissue explants from the subcutaneous and omental fat compartments; 2) To assess which PGF synthase is the most relevant in human adipose tissue. METHODS: Fat samples were obtained by surgery in women. PGF2α release by preadipocytes, adipocytes and explants under stimulation by TNF-α, IL-1ß or both was measured. Messenger RNA expression levels of AKR1B1 and AKR1C3 were measured by RT-PCR in whole adipose tissue and cytokine-treated preadipocytes. The effect of AKR1B1 inhibitor ponalrestat on PGF2α synthesis was investigated. RESULTS: PGF2α release was significantly induced in response to cytokines compared to control in omental (p = 0.01) and to a lesser extent in subcutaneous preadipocytes (p = 0.02). Messenger RNA of COX-2 was significantly higher in omental compared to subcutaneous preadipocytes in response to combined TNF-α and IL-1ß (p = 0.01). Inflammatory cytokines increased AKR1B1 mRNA expression and protein levels (p≤0.05), but failed to increase expression levels of AKR1C3 in cultured preadipocytes. Accordingly, ponalrestat blunted PGF2α synthesis by preadipocytes in basal and stimulated conditions (p≤0.05). Women with the highest PGF2α release by omental adipocytes had a higher BMI (p = 0.05), waist circumference (p≤0.05) and HOMAir index (p≤0.005) as well as higher mRNA expression of AKR1B1 in omental (p<0.10) and subcutaneous (p≤0.05) adipose tissue compared to women with low omental adipocytes PGF2α release. Positive correlations were observed between mRNA expression of AKR1B1 in both compartments and BMI, waist circumference as well as HOMAir index (p≤0.05 for all). CONCLUSION: PGF2α release by omental mature adipocytes is increased in abdominally obese women. Moreover, COX-2 expression and PGF2α release is particularly responsive to inflammatory stimulation in omental preadipocytes. Yet, blockade of PGF synthase AKR1B1 inhibits most of the PGF2α release.

Markers of macrophage infiltration and measures of lipolysis in human abdominal adipose tissues.

OBJECTIVE: We tested the hypothesis that high lipolytic responsiveness is related to increased expression of ATM genes in human adipose tissues. DESIGN AND METHODS: Omental (OM) and subcutaneous (SC) fat samples were obtained surgically in 46 women (age: 47.2 ± 4.7 years, BMI: 26.9 ± 5.2 kg/m(2) ). Body composition and fat distribution were measured using dual energy X-ray absorptiometry and computed tomography. Lipolysis was measured by glycerol release in mature adipocytes isolated by collagenase digestion under basal-, isoproterenol (10(-5) M)-, and forskolin (10(-5) M)-stimulated conditions. Quantification of macrophage gene mRNA expression (CD11b, CD11c, and CD68) in whole adipose tissue was performed using real-time RT-PCR. RESULTS: SC CD68 mRNA abundance was positively associated with isoproterenol-stimulated lipolysis (r = 0.36, P < 0.05). This association remained significant after adjustment for total body fat mass (r = 0.34, P ≤ 0.05). In the OM depot, CD11b mRNA abundance was positively associated with isoproterenol-stimulated lipolysis (r = 0.42, P ≤ 0.005). This association remained significant after adjustment for total body fat mass (r = 0.41, P ≤ 0.01). In subgroup analyses, high lipolytic rates in SC adipocytes were related to increased whole tissue expression of CD68 and CD11b in this compartment, independent of adiposity and fat cell size (P ≤ 0.001 and P ≤ 0.05). High lipolytic rates in OM adipocytes were related to increased whole tissue OM expression of CD11b, independent of adiposity and fat cell size (P ≤ 0.05). CONCLUSIONS: High adipocyte lipolytic responsiveness is related to increased expression of ATM markers in the corresponding compartment, independent of adiposity and fat cell size.

Visceral fat accumulation is an indicator of adipose tissue macrophage infiltration in women.

We tested the hypothesis that visceral obesity is the best correlate of abdominal adipose tissue macrophage infiltration in women. Omental and subcutaneous fat samples were surgically obtained from 40 women (age, 47.0 ± 4.0 years; body mass index, 28.4 ± 5.8 kg/m(2)). CD68+ cells were identified using fluorescence immunohistochemistry. Expression of macrophage markers was measured by real-time reverse transcriptase polymerase chain reaction. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography, respectively. Mean CD68+ cell percentage tended to be higher in subcutaneous (18.3%) compared with omental adipose tissue (15.5%, P = .07). Positive correlations were observed between CD68+ cell percentage as well as CD68 messenger RNA expression in a given depot vs the other (P ≤ .01). Visceral adipose tissue area and omental adipocyte diameter were positively related to CD68+ cell percentage in omental fat (r = 0.52 and r = 0.35, P ≤ .05). Total and visceral adipose tissue areas as well as subcutaneous adipocyte diameter were significantly correlated with CD68+ cell percentage in subcutaneous adipose tissue (0.32 ≤ r ≤ 0.40, P ≤ .05). Adipose tissue areas and subcutaneous adipocyte diameter were also significantly associated with expression of commonly used macrophage markers including CD68 in the subcutaneous fat compartment (0.32 ≤ r ≤ 0.57, P ≤ .05). Visceral adipose tissue area was the best correlate of CD68+ cell percentage in both omental and subcutaneous fat tissues, explaining, respectively, 20% and 12% of the variance in models also including subcutaneous adipose tissue area, adipocyte sizes, and total body fat mass. Visceral adipose tissue accumulation is the best correlate of macrophage infiltration in both the subcutaneous and omental fat compartments of lean to obese women.