Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery.

Obesity and overnutrition during pregnancy affect fetal programming of adult disease. Children born after maternal bariatric gastrointestinal bypass surgery (AMS) are less obese and exhibit improved cardiometabolic risk profiles carried into adulthood compared with siblings born before maternal surgery (BMS). This study was designed to analyze the impact of maternal weight loss surgery on methylation levels of genes involved in cardiometabolic pathways in BMS and AMS offspring. Differential methylation analysis between a sibling cohort of 25 BMS and 25 AMS (2-25 y-old) offspring from 20 mothers was conducted to identify biological functions and pathways potentially involved in the improved cardiometabolic profile found in AMS compared with BMS offspring. Links between gene methylation and expression levels were assessed by correlating genomic findings with plasma markers of insulin resistance (fasting insulin and homeostatic model of insulin resistance). A total of 5,698 genes were differentially methylated between BMS and AMS siblings, exhibiting a preponderance of glucoregulatory, inflammatory, and vascular disease genes. Statistically significant correlations between gene methylation levels and gene expression and plasma markers of insulin resistance were consistent with metabolic improvements in AMS offspring, reflected in genes involved in diabetes-related cardiometabolic pathways. This unique clinical study demonstrates that effective treatment of a maternal phenotype is durably detectable in the methylome and transcriptome of subsequent offspring.

Intestinal lipid handling: evidence and implication of insulin signaling abnormalities in human obese subjects.

OBJECTIVE: Animal models have evidenced the role of intestinal triglyceride-rich lipoprotein overproduction in dyslipidemia. However, few studies have confronted this issue in humans and disclosed the intrinsic mechanisms. This work aimed to establish whether intestinal insulin resistance modifies lipid and lipoprotein homeostasis in the intestine of obese subjects. APPROACH AND RESULTS: Duodenal specimens obtained from 20 obese subjects undergoing bariatric surgery were paired for age, sex, and body mass index with or without insulin resistance, as defined by the homeostasis model assessment of insulin resistance. Insulin signaling, biomarkers of inflammation and oxidative stress, and lipoprotein assembly were assessed. The intestine of insulin-resistant subjects showed defects in insulin signaling as demonstrated by reduced protein kinase B phosphorylation and increased p38 mitogen-activated protein kinase phosphorylation, likely as the result of high oxidative stress (evidenced by malondialdehyde and conjugated dienes) and inflammation (highlighted by nuclear factor-κB, tumor necrosis factor-α, interleukin-6, intercellular adhesion molecule-1, and cyclooxygenase-2). Enhanced de novo lipogenesis rate and apolipoprotein B-48 biogenesis along with exaggerated triglyceride-rich lipoprotein production were observed, concomitantly with the high expression levels of liver and intestinal fatty acid-binding proteins and microsomal transfer protein. The presence of an aberrant intracellular cholesterol transport/metabolism was also suggested by the reduced expression of ATP-binding cassette A1 transporter and proprotein convertase subtilisin/kexin type 9. CONCLUSIONS: According to the present data, the small intestine may be classified as an insulin-sensitive tissue. Dysregulation of intestinal insulin signaling, possibly triggered by oxidative stress and inflammation, was associated with exaggerated lipogenesis and lipoprotein synthesis, which may represent a key mechanism for atherogenic dyslipidemia in patients with metabolic syndrome.

Cross-sectional associations of acylation stimulating protein (ASP) and adipose tissue gene expression with estradiol and progesterone in pre- and postmenopausal women.

OBJECTIVE: Sex steroid hormones play an important regulatory role in fat metabolism and obesity. We hypothesized involvement of interactions between ovarian hormones with acylation stimulating protein (ASP). DESIGN, PATIENTS AND MEASUREMENTS: In 392 women with wide age (18-69 years) and body size (BMI: 17 to 90 kg/m(2) ) ranges, fasting plasma levels of ASP, ovarian hormones, glucose, adiponectin and lipids/apolipoproteins were assessed, along with determination of metabolic syndrome (MS) features. Gene expression of C3 (ASP precursor) and related receptors C5L2, C3aR and C5aR in subcutaneous and omental adipose tissues was measured in a subset. RESULTS: Acylation stimulating protein correlated negatively with concentrations of estradiol (P < 0·0001), adiponectin (P < 0·001) and apolipoprotein A1 (P < 0·001) and positively with apolipoprotein B levels (P < 0·001), systolic blood pressure (P < 0·001), waist circumference (P < 0·001), and triglyceride concentrations (P < 0·01). In age-matched groups of lean, overweight, metabolically healthy obese (MHO) and obese with metabolic syndrome (MSO), there was a stepwise increase in ASP levels (P < 0·001) while concentrations of adiponectin (P < 0·0001) and estradiol (P < 0·001) but not those of progesterone decreased. Progesterone but not estradiol levels correlated positively with C3 gene expression in omental adipose tissue (P < 0·05) and negatively with C5L2 expression in both omental (P < 0·01) and subcutaneous (P < 0·05) adipose tissues. CONCLUSION: Our results are consistent with the concept that sex hormones differentially influence circulating ASP and adipose tissue gene expression of its related proteins in a depot-specific manner. ASP may play a role in the regulation of regional fat metabolism through interactions with sex hormones in women.

Association of immune and metabolic receptors C5aR and C5L2 with adiposity in women.

Adipose tissue receptors C5aR and C5L2 and their heterodimerization/functionality and interaction with ligands C5a and acylation stimulating protein (ASP) have been evaluated in cell and rodent studies. Their contribution to obesity factors in humans remains unclear. We hypothesized that C5a receptors, classically required for host defense, are also associated with adiposity. Anthropometry and fasting blood parameters were measured in 136 women divided by body mass index (BMI): normal/overweight (≤30 kg/m(2); n = 34), obese I (≤45 kg/m(2); n = 33), obese II (≤51 kg/m(2); n = 33), and obese III (≤80 kg/m(2); n = 36). Subcutaneous and omental adipose tissue C5aR and C5L2 expression were analysed. C5L2 expression was comparable between subcutaneous and omental across all BMI groups. Plasma ASP and ASP/omental C5L2 expression increased with BMI (P < 0.001 and P < 0.01, resp.). While plasma C5a was unchanged, C5aR expression decreased with increasing BMI in subcutaneous and omental tissues (P < 0.01 and P < 0.05, resp.), with subcutaneous omental depots. Omental C5L2/C5aR ratio increased with BMI (P < 0.01) with correlations between C5L2/C5aR and waist circumference, HDL-C, and adiponectin. Tissue and BMI differences in receptors and ligands, particularly in omental, suggest relationship to metabolic disturbances and highlight adipose-immune interactions.

Glucocorticoid-induced androgen inactivation by aldo-keto reductase 1C2 promotes adipogenesis in human preadipocytes.

Adipogenesis and lipid storage in human adipose tissue are inhibited by androgens such as DHT. Inactivation of DHT to 3α-diol is stimulated by glucocorticoids in human preadipocytes. We sought to characterize glucocorticoid-induced androgen inactivation in human preadipocytes and to establish its role in the antiadipogenic action of DHT. Subcutaneous and omental primary preadipocyte cultures were established from fat samples obtained in subjects undergoing abdominal surgeries. Inactivation of DHT to 3α/ß-diol for 24 h was measured in dexamethasone- or vehicle-treated cells. Specific downregulation of aldo-keto reductase 1C (AKR1C) enzymes in human preadipocytes was achieved using RNA interference. In whole adipose tissue sample, cortisol production was positively correlated with androgen inactivation in both subcutaneous and omental adipose tissue (P < 0.05). Maximal dexamethasone (1 µM) stimulation of DHT inactivation was higher in omental compared with subcutaneous fat from men as well as subcutaneous and omental fat from women (P < 0.05). A significant positive correlation was observed between BMI and maximal dexamethasone-induced DHT inactivation rates in subcutaneous and omental adipose tissue of men and women (r = 0.24, n = 26, P < 0.01). siRNA-induced downregulation of AKR1C2, but not AKR1C1 or AKR1C3, significantly reduced basal and glucocorticoid-induced androgen inactivation rates (P < 0.05). The inhibitory action of DHT on preadipocyte differentiation was potentiated following AKR1C2 but not AKR1C1 or AKR1C3 downregulation. Specifically, lipid accumulation, G3PDH activity, and FABP4 mRNA expression in differentiated preadipocytes exposed to DHT were reduced further upon AKR1C2 siRNA transfection. We conclude that glucocorticoid-induced androgen inactivation is mediated by AKR1C2 and is particularly effective in omental preadipocytes of obese men. The interplay between glucocorticoids and AKR1C2-dependent androgen inactivation may locally modulate adipogenesis and lipid accumulation in a depot-specific manner.

Genetic contribution to C-reactive protein levels in severe obesity.

Obese individuals are characterized by a chronic, low-grade inflammatory state. Increased levels of C-reactive protein (CRP), a marker of inflammation, have been observed in subjects with the metabolic syndrome. We have previously reported that genes encoding proteins involved in the anti-inflammatory and immune response are differentially expressed in visceral adipose tissue of obese men with or without the metabolic syndrome. Among these genes, the interferon-gamma-inducible protein 30 (IFI30), CD163 molecule (CD163), chemokine (C-X-C motif) ligand 9 (CXCL9) and thymic stromal lymphopoietin (TSLP), were selected for further genetic analyses. The aim of the study was to verify whether IFI30, CD163, CXCL9 and TSLP gene polymorphisms contribute to explain the inter-individual variability of the inflammatory profile of obesity assessed by plasma high-sensitivity CRP concentrations. A total of 1185 severely obese individuals were genotyped for single nucleotide polymorphisms (SNPs) covering most of the sequence-derived genetic variability at the IFI30, CD163, CXCL9 and TSLP gene loci (total of 27 SNPs). Following measurement of plasma CRP levels, subjects were divided into two groups, low vs. high using the median value of plasma CRP levels (8.31 mg/L) as a cutoff point. Genotype frequencies were compared between groups. Associations between genotypes and plasma CRP levels (continuous variable) were also tested after adjustments for age, sex, smoking and BMI. The rs11554159 and rs7125 IFI30 SNPs showed a significant difference in genotype frequencies (p<0.05) between subgroups of low vs. high plasma CRP levels (wild type homozygotes: rs11554159=47% vs. 55%, rs7125=31% vs. 24%, for low vs. high CRP groups, respectively). The association between rs11554159 and CRP levels as a continuous variable remained significant (p=0.004). Both carriers of the GA and AA genotypes demonstrated, on average, a 13% lower CRP levels in comparison with GG homozygotes. No association was observed between SNPs in the CD163, CXCL9 and TSLP genes and CRP levels. The IFI30 rs11554159 polymorphism could partially explain the inter-individual variability observed in the inflammatory profile associated with obesity.

The laval questionnaire: a new instrument to measure quality of life in morbid obesity.

BACKGROUND: Our recent review of the literature uncovered eleven obesity-specific quality of life questionnaires, all with incomplete demonstration of their measurement properties. Our objective was to validate a new self-administered questionnaire specific to morbid obesity to be used in clinical trials. The study was carried out at the bariatric surgery clinic of Laval Hospital, Quebec City, Canada. METHODS: This study followed our description of health-related quality of life in morbid obesity from which we constructed the Laval Questionnaire. Its construct validity and responsiveness were tested by comparing the baseline and changes at 1-year follow-up in 6 domain scores (symptoms, activity/mobility, personal hygiene/clothing, emotions, social interactions, sexual life) with those of questionnaires measuring related constructs (SF-36, Impact of Weight on Quality of Life-Lite, Rosenberg Self-Esteem Scale and Beck Depression Inventory-II). RESULTS: 112 patients (67 who got bariatric surgery, 45 who remained on the waiting list during the study period) participated in this study. The analysis of the discriminative function of the questionnaire showed moderate-to-high correlations between the scores in each domain of our instrument and the corresponding questionnaires. The analysis of its evaluative function showed (1) significant differences in score changes between patients with bariatric surgery and those without, and (2) moderate-to-high correlations between the changes in scores in the new instrument and the changes in the corresponding questionnaires. Most of these correlations met the a priori predictions we had made regarding their direction and magnitude. CONCLUSION: The Laval Questionnaire is a valid measure of health-related quality of life in patients with morbid obesity and is responsive to treatment-induced changes.

Cardiovascular evaluation and management of severely obese patients undergoing surgery: a science advisory from the American Heart Association.

Obesity is associated with comorbidities that may lead to disability and death. During the past 20 years, the number of individuals with a body mass index >30, 40, and 50 kg/m(2), respectively, has doubled, quadrupled, and quintupled in the United States. The risk of developing comorbid conditions rises with increasing body mass index. Possible cardiac symptoms such as exertional dyspnea and lower-extremity edema occur commonly and are nonspecific in obesity. The physical examination and electrocardiogram often underestimate cardiac dysfunction in obese patients. The risk of an adverse perioperative cardiac event in obese patients is related to the nature and severity of their underlying heart disease, associated comorbidities, and the type of surgery. Severe obesity has not been associated with increased mortality in patients undergoing cardiac surgery but has been associated with an increased length of hospital stay and with a greater likelihood of renal failure and prolonged assisted ventilation. Comorbidities that influence the preoperative cardiac risk assessment of severely obese patients include the presence of atherosclerotic cardiovascular disease, heart failure, systemic hypertension, pulmonary hypertension related to sleep apnea and hypoventilation, cardiac arrhythmias (primarily atrial fibrillation), and deep vein thrombosis. When preoperatively evaluating risk for surgery, the clinician should consider age, gender, cardiorespiratory fitness, electrolyte disorders, and heart failure as independent predictors for surgical morbidity and mortality. An obesity surgery mortality score for gastric bypass has also been proposed. Given the high prevalence of severely obese patients, this scientific advisory was developed to provide cardiologists, surgeons, anesthesiologists, and other healthcare professionals with recommendations for the preoperative cardiovascular evaluation, intraoperative and perioperative management, and postoperative cardiovascular care of this increasingly prevalent patient population.

Effects of androgens on adipocyte differentiation and adipose tissue explant metabolism in men and women.

OBJECTIVE: To examine the effects of aromatizable or nonaromatizable androgens on abdominal subcutaneous (SC) and omental (OM) adipose tissue lipid metabolism and adipogenesis in men and women. DESIGN AND SUBJECTS: Primary organ and preadipocyte cultures were established from surgical samples obtained in men (n = 22) and women undergoing biliopancreatic diversions (n = 12) or gynaecological surgeries (n = 8). Cultures were treated with testosterone, dihydrotestosterone (DHT) and methyltrienolone (R1881). MEASUREMENTS: Heparin-releasable lipoprotein lipase (HR-LPL) activity, glycerol release, adiponectin secretion, glycerol-3-phosphate dehydrogenase activity and lipid accumulation were measured. RESULTS: In organ cultures from men, DHT had a statistically significant inhibitory effect on HR-LPL activity in the OM compartment. Testosterone significantly inhibited HR-LPL activity in SC and OM cultures. In women, high DHT concentrations tended to inhibit HR-LPL activity in OM cultures. Minor androgenic effects were observed for basal and isoproterenol-stimulated lipolysis as well as adiponectin release in men. On the other hand, adipocyte differentiation was significantly and dose-dependently inhibited by DHT, testosterone and R1881 in SC and OM cultures from both sexes. These effects did not differ according to adipose tissue depot but appeared to be more pronounced in women than in men. CONCLUSIONS: Androgens slightly decreased HR-LPL activity in adipose tissue organ cultures, but markedly inhibited adipogenesis in SC and OM primary preadipocyte cultures in both sexes. Androgenic effects on adipose tissue in men vs. women may not differ in terms of direction but in the magnitude of their negative impact on adipogenesis and lipid synthesis.

Comparison of Short and Long Term Cardiovascular Outcomes After Bariatric Surgery in Patients With vs Without Coronary Artery Disease.

There is little data regarding the risks and benefits of bariatric surgery in patients with coronary artery disease (CAD). We aimed to assess the short- and long-term cardiovascular outcomes of patients with CAD undergoing bariatric surgery. Patients with a history of CAD were identified from a dedicated database with prospectively collected outcomes, comprising all 6795 patients who underwent bariatric surgery between January 1992 and October 2017. Patients were matched with patients who did not have CAD before the bariatric surgery procedure. The primary endpoints were mortality (cardiac and noncardiac) and major adverse cardiocerebral events (MACCE), including all-cause death, myocardial infarction, stroke, and myocardial revascularization at 30 days after bariatric surgery and throughout follow-up. After propensity score matching, 249 patients with chronic CAD were matched with 249 patients without CAD. Throughout follow-up (7.4 years; interquartile range 4.1 to 11.5, maximum 22 years), mortality (mainly cardiac mortality) remained significantly higher in the CAD compared with the non-CAD group (18% vs 10%, hazard ratio [HR] 1.70, 95% confidence interval [CI]: 1.03 to 2.79, p = 0.037). At 30 days, MACCE rate was significantly higher in the CAD compared with the non-CAD group (3.6% vs 0.4%, p = 0.011), essentially driven by non-ST elevation myocardial infarctions. After 30 days, MACCE rates remained significantly higher in the CAD group (30% vs 14%, HR 2.18, 95% CI: 1.45-3.28, p = 0.0002). In conclusion, patients with severe obesity and CAD referred to bariatric surgery were at a higher risk of early and late MACCE compared with non-CAD severely obese patients. Further study is required to define how this cardiovascular risk compares with nonoperated patients.

Duodenal switch improved standard biliopancreatic diversion: a retrospective study.

BACKGROUND: This was a retrospective study, performed 10 years after surgery, to compare the results between biliopancreatic diversion (BPD) with distal gastrectomy (DG) versus BPD with duodenal switch (DS). METHODS: Complete follow-up data were available for 96% of patients, allowing a comparison of weight loss, revision, side effects, and complications at 10 years. RESULTS: After BPD-DS, weight loss was 25% greater than after BPD-DG (46.8 +/- 21.7 kg versus 37.5 +/- 22 kg, respectively; P <.0001). The need for revision decreased from 18.5% to 2.7% (P <.0001), and the prevalence of vomiting during the previous month was 50% less (23.7-50.6%, P <.0001) after BPD-DS compared with after BPD-DG. Late complications were the same for both procedures. Blood analysis showed that, after BPD-DS, the levels of calcium, iron, and hemoglobin were significantly greater and the parathyroid hormone level was lower than after BPD-DG (71.3 +/- 44.2 versus 103.0 +/- 64.0 ng/L, respectively; P <.0001). CONCLUSION: The DS greatly improved the BPD, as it was initially proposed. The use of the DS increased weight loss, decreased the need for revision, resulted in fewer side effects, and improved the absorption of nutrients.

Muscle force and force control after weight loss in obese and morbidly obese men.

BACKGROUND: Decrease in fat mass and fat-free mass have been observed with weight loss induced by a dietary intervention or surgery. There are concerns that fat-free mass decrease could have some negative functional consequences. The aim of this study was to examine how weight loss affects strength and force control in obese and morbidly obese men. METHODS: Weight loss was obtained in obese individuals by a hypocaloric diet program until resistance to lose fat and in morbidly obese individuals by bariatric surgery. Maximal force was measured for upper and lower limb and the ability to maintain 15% and 40% of that force. These measures were taken at baseline, in those dieting once resistant to weight loss and 1 year after surgery for those operated on. Normal weight individuals used for control were evaluated twice (6 to 12 months apart). RESULTS: At baseline, there was no significant difference between groups for maximal forces and capabilities to maintain force levels. Weight loss averaged 11.1% of the initial body weight after dieting and 46.3% 1 year after surgery. At the same time, there was for the lower limb a loss of 10.1% in maximal force after dieting and 33.5% after surgery. For the upper limb, there was no change in maximal force after dieting whereas a decrease of 14.4% was observed after surgery. When transformed in force related to body weight, there was no change in relative force for the lower limb after dieting whereas an increased relative force after surgery. There was no significant difference for the ability for maintaining force levels. CONCLUSION: Despite a large force loss, particularly for the lower limbs in morbidly obese individuals after surgery, this loss is relatively well tolerated because the relation between force and body weight is even improved and the ability to maintain that force is preserved.

Body weight and satiation after duodenal switch: 2 years later.

BACKGROUND: The authors investigated body weight, satiation, and gustative pleasure of obese patients 2 years after a bariatric operation: the biliopancreatic diversion with duodenal switch (DS). METHODS: 9 operated patients, 10 unoperated non-obese and 10 unoperated obese persons participated in the "alliesthesia (food distaste) test". This test is a psychometric assessment of satiation resulting from the pleasure or displeasure following the repeated ingestion of a sweet stimulus. Operated patients also participated in the test before the DS operation. RESULTS: 2 years after DS, patients had lost 50% of their body weight and their BMI was rendered similar to that of the non-obese control group. Their satiation was faster than in control and unoperated obese patients. The responses of control and unoperated obese patients were identical to those of pre-surgery operated patients. CONCLUSION: This indicates that at the time of the experiment, patients' actual body weight was higher than their body weight set-point and that they would be likely to continue to lose weight, at least beyond 2 years.

Duodenal switch: long-term results.

BACKGROUND: This report summarizes our 15-year experience with duodenal switch (DS) as a primary procedure on 1,423 patients from 1992 to 2005. METHODS: Within the last 2 years, follow-up of these patients, including clinical biochemistry evaluation by us or by their local physician is 97%. RESULTS: Survival rate was 92% after DS. The risk of death (Excess Hazard Ratio (EHR)) was 1.2, almost that of the general population. After a mean of 7.3 years (range 2-15), 92% of patients with an initial BMI < or = 50 kg/m2 obtained a BMI < 35 and 83% of those with an initial BMI > 50 obtained a BMI < 40. Diabetes was cured (i.e. medication was discontinued) in 92% and medication decreased in the others. The use of the CPAP apparatus was discontinued in 90%, medication for asthma was decreased in 88%, and the prevalence of a cardiac risk index > 5 was decreased by 86%. Patients' satisfaction in regard to weight loss was graded 3.6 on a basis of 5, and 95% of patients were satisfied with the overall results. Operative mortality was 1% which is comparable with gastric bypass surgery. The need for revision for malnutrition was rare (0.7%) and total reversal was exceptional (0.2%). Failure to lose > 25% of initial excess weight was 1.3%. Revision for failure to lose sufficient weight was needed in only 1.5%. Severe anemia, deficiency in vitamins or bone damage were exceptional, easily treatable, preventable and no permanent damage was documented. CONCLUSION: In the long-term, DS was very efficient in terms of cure rate for morbid obesity and its comorbidities. In terms of risk/benefit, DS was very sucessful with an appropriate system of follow-up.

Waist circumference is useless to assess the prevalence of metabolic abnormalities in severely obese women.

BACKGROUND: The present retrospective study aims to provide additional evidence supporting the fact that waist circumference, in severe obesity, is not a good clinical marker to identify individuals with the metabolic syndrome or an altered metabolic profile. METHODS: Relationships between waist circumference and metabolic profile of pre- (n=165) and postmenopausal (n=43) severely obese women were compared to associations observed in pre- (n=52) and postmenopausal (n=35) moderately obese women. RESULTS: Results showed that abdominal obesity assessed by waist circumference was more highly correlated with fasting glycemia, HDL-cholesterol and the cholesterol/HDL-cholesterol ratio in moderately than in severely obese women, before menopause. After menopause, waist circumference was not a valuable predictor of metabolic abnormalities in both groups. Moreover, when waist circumference was included as a criterion of the metabolic syndrome (as defined by the NCEP ATP III guidelines) in severely obese women, the prevalence of this metabolic condition was over-estimated by 72%. CONCLUSION: These results emphasize the uselessness of waist circumference to assess the prevalence of the metabolic syndrome or an altered metabolic profile in severely obese women.

Regional differences in adipose tissue metabolism in obese men.

We examined omental and subcutaneous adipose tissue adipocyte size, and lipolysis and lipoprotein lipase (LPL) activity in a sample of 33 men aged 22.6 to 61.2 years and with a body mass index ranging from 24.6 to 79.1 kg/m2. We tested the hypothesis that lipolysis rates would be higher in the omental fat depot than in subcutaneous adipose tissue and that this difference would persist across the spectrum of abdominal adiposity values. Omental and subcutaneous adipose tissue samples were obtained during surgery. Adipocytes were isolated by collagenase digestion. Adipocyte size and LPL activity as well as basal, isoproterenol-, forskolin-, and dibutyryl cyclic adenosine monophosphate-stimulated lipolysis were measured. Although adipocytes from both fat compartments were larger in obese subjects, no difference was observed in the size of omental vs subcutaneous fat cells. Lipoprotein lipase activity, expressed as a function of cell number, was significantly higher in omental than in subcutaneous fat tissue (P<.005). Basal lipolysis and lipolytic responses to isoproterenol, forskolin, or dibutyryl cyclic adenosine monophosphate, expressed either as a function of cell number or as a fold response over basal levels, were not significantly different in omental vs subcutaneous fat cells. When stratifying the sample in tertiles of waist circumference, adipocyte diameter was similar in the omental and subcutaneous depots for all adiposity values. Omental adipocyte size reached a plateau in the 2 upper tertiles of waist circumference, that is, from a waist circumference of 125 cm and above. Lipoprotein lipase activity was significantly higher in omental cells in the middle tertile of waist circumference (P=.05), and no regional difference was noted in lipolysis values across waist circumference tertiles. In conclusion, in normal-weight to morbidly obese men, although adipocyte size and lipolysis tended to increase with higher waist circumference, no difference was observed between the omental and subcutaneous fat depot.

Impact of bariatric surgery--induced weight loss on heart rate variability.

Obesity is associated with an increased risk of sudden death that may be due to abnormal cardiac vagal modulation reflected by reduced heart rate variability (HRV). Few studies have been conducted analyzing the effect of bariatric surgery-induced weight loss on HRV assessed by 24-hour Holter monitoring. The aim of this study was to assess weight loss effect after bariatric surgery on HRV and ventricular size and function. Ten morbidly obese patients, 6 women and 4 men aged 24 to 47 years, underwent bariatric surgery. Seven morbidly obese patients without active obesity treatment were used as controls. Twenty-four-hour Holter monitoring and echocardiogram were obtained before and at 6 to 12 months after surgery or at follow-up in control patients. Changes in minimal, maximal, and mean heart rate along with HRV during daytime and nighttime were compared before and after surgery. Baseline characteristics in the control group did not differ significantly from the treatment group. Average weight in the treatment group was 141 +/- 31 kg (mean +/- SD) at baseline and decreased to 101 +/- 18 kg at follow-up, corresponding to a body mass index of 52.3 +/- 7.6 kg/m(2) at baseline and 37.7 +/- 5.3 kg/m(2) at follow-up. There was a decrease in minimal heart rate (48 +/- 10 vs 40 +/- 6 beats per minute, P = .021) and mean heart rate (82 +/- 7 vs 66 +/- 10 beats per minute, P < .001) during the Holter monitoring. Spectral analysis showed a significant enhancement in HRV parameters (high- and low-frequency power) because there was an increase in the standard deviation of normal to normal R-R intervals (116 +/- 25 vs 174 +/- 56 milliseconds, P < .001), the standard deviation of the mean R-R intervals calculated over a 5-minute period (104 +/- 25 vs 148 +/- 45 milliseconds, P < .001), the square root of the mean of the squared differences between adjacent normal R-R intervals (25 +/- 8 vs 50 +/- 20 milliseconds, P < .001), and the percentage of differences between adjacent normal R-R intervals exceeding 50 milliseconds (5% +/- 5% vs 22% +/- 13%, P < .001). Echocardiographic measures remained unchanged when comparing the groups. Weight loss after bariatric surgery enhances HRV and decreases mean and minimal heart rate during Holter monitoring through a better cardiac parasympathetic modulation.

Gene expression variability in subcutaneous and omental adipose tissue of obese men.

We investigated interindividual variability in gene expression in abdominal subcutaneous (SC) and omental (OM) adipose tissue of 10 massively obese men. Affymetrix human U133A microarrays were used to measure gene expression levels. A total of 6811 probesets generated significant signal in both depots in all samples. Interindividual variability in gene expression was rather low, with more than 90% of transcripts showing a coefficient of variation (CV) lower than 23.6% and 21.7% in OM and SC adipose tissues, respectively. The distributions of CV were similar between the two fat depots. A set of highly variable genes was identified for both tissues on the basis of a high CV and elevated gene expression level. Among the set of highly regulated genes, 18 transcripts were involved in lipid metabolism and 28 transcripts were involved in cell death for SC and OM samples, respectively. In conclusion, gene expression interindividual variability was rather low and globally similar between fat compartments, and the adipose tissue transcriptome appeared as relatively stable, although specific pathways were found to be highly variable in SC and OM depots.

Body weight is a strong predictor of postural stability.

Proper balance control is a key aspect of acitivities of daily living. The aim of this study was to determine the contribution of body weight to predict balance stability. The balance stability of 59 male subjects with BMI ranging from 17.4 to 63.8kg/m(2) was assessed using a force platform. The subjects were tested with and without vision. A stepwise multiple regression analysis was used to determine the independent effect of body weight, age, body height and foot length on balance stability (i.e., mean speed of the center of foot pressure). With vision, the stepwise multiple regression revealed that body weight accounted for 52% of the variance of balance stability. The addition of age contributed a further 3% to explain balance control. Without vision, body weight accounted for 54% of the variance and the addition of age and body height added a further 8% and 1% to explain the total variance, respectively. The final model explained 63% of the variance. A decrease in balance stability is strongly correlated to an increase in body weight. This suggests that body weight may be an important risk factor for falling. Future studies should examine more closely the combined effect of aging and obesity on falling and injuries and the impact of obesity on the diverse range of activities of daily living.

Plasma concentration of organochlorine compounds is associated with age and not obesity.

It has been suggested that obese individuals, because of an increased dilution space (body fat) for lipophilic organochlorines compounds, may have greater levels of toxic pollutants than lean sedentary individuals. It is important to further examine this possibility because of the potential contribution of organochlorine pesticides in the development of Parkinson's disease and other neurological diseases. The aim of this study was to further investigate the relationship between the magnitude of obesity and the plasma concentration of organochlorines for a wide range of BMI (with participants at steady state body weight). Fifty-three individuals were selected on the basis of their body mass index (BMI): lean controls (n=16; mean BMI 22.8+/-2.2 kg/m(2); mean age 38.8+/-9.4 years), obese individuals (n=19; mean BMI 33.4+/-3.0 kg/m(2); mean age 38.6+/-7.6 years) and morbidly obese individuals (n=18; mean BMI 49.3+/-6.5 kg/m(2); mean age 44.3+/-9.2 years). Blood samples were analyzed for organochlorine compounds. The relationship between the total plasma organochlorine concentration and BMI was tested using a multiple regression analysis. Age was included in the model. There was no relationship between the total plasma organochlorine concentration and BMI. Organochlorine concentrations, however, were correlated with age (BMI-adjusted R(2)=0.46; p<0.001). At steady state body weight, toxic pollutant concentrations are not associated to obesity but strongly correlate with age.