Post-obese Subjects Research Articles

Upregulated TNF Expression 1\xa0Year After Bariatric Surgery Reflects a Cachexia-Like State in Subcutaneous Adipose Tissue

BackgroundAdipose tissue dysfunction contributes to obesity-associated chronic diseases. In the first year after bariatric surgery, obese patients significantly improve their metabolic status upon losing weight. We aimed to investigate whether changes in subcutaneous adipose tissue gene expression reflect a restoration of a healthy lean phenotype after bariatric surgery.MethodsThirty-one severely obese patients (BMI ≥ 40 kg/m2) were examined before and after surgery. subcutaneous adipose tissue (SAT) was collected during and 1 year after bariatric surgery. SAT from 20 matched lean and overweight patients (BMI < 30 kg/m2) was collected during elective abdominal surgery. Baseline characteristics and SAT gene expression relevant to glucose and lipid metabolism, inflammation, and apoptosis were analyzed.ResultsAfter surgery, mean BMI decreased from 46.1 ± 6.3 to 31.1 ± 5.7 kg/m2 and homeostasis model assessment of insulin resistance from 5.4 ± 5.3 to 0.8 ± 0.8. SAT expression of most analyzed inflammatory cytokines, growth factors, and metabolic and cell surface markers was greatly downregulated even compared to the lean cohort. In contrast, gene expression of TNF and CASP3 was significantly upregulated. Elastic net regression analysis showed that fasting glucose levels and CASP3 predicted increased TNF expression in the post-obese group.ConclusionsGene expression patterns in SAT 1 year after bariatric surgery point to a reduced inflammation. The unexpected high TNF expression in SAT of post-obese subjects is most likely not an indicator for inflammation, but rather an indicator for increased lipolysis and adipose tissue catabolism. Notably, after bariatric surgery SAT gene expression reflects a cachexia-like phenotype and differs from the lean state.

Ceramide content is higher in type I compared to type II fibers in obesity and type 2 diabetes mellitus

This study investigated fiber-type-specific muscle ceramide content in obese subjects and type 2 diabetes patients. Two substudies, one which compared type 2 diabetes patients to both lean- and obese BMI-matched subjects and the other study which compared lean body-matched post-obese, obese, and control subjects, were performed. A fasting blood sample was obtained and plasma insulin and glucose determined. A muscle biopsy was obtained from deltoideus and vastus lateralis, and fiber-type ceramide content was determined by fluorescence immunohistochemistry. Insulin sensitivity estimated by Quicki index was higher in lean compared to type 2 diabetes patients and obese controls. Also in control and post-obese subjects, a higher insulin sensitivity was observed compared to obese subjects. Ceramide content was consistently higher in type I than in type II muscle fibers and higher in deltoideus than vastus lateralis across all groups. No significant differences between groups were observed in ceramide content in either of the two substudies. In human skeletal muscle, ceramide content was higher in type I than in type II fibers in patients with type 2 diabetes and in obese subjects, but overall ceramide muscle fiber content was not different compared to controls.

Normal mitochondrial function and increased fat oxidation capacity in leg and arm muscles in obese humans

The aim of this study was to investigate mitochondrial function, fibre-type distribution and substrate oxidation during exercise in arm and leg muscles in male postobese (PO), obese (O) and age- and body mass index (BMI)-matched control (C) subjects. The hypothesis of the study was that fat oxidation during exercise might be differentially preserved in leg and arm muscles after weight loss. Indirect calorimetry was used to calculate fat and carbohydrate oxidation during both progressive arm-cranking and leg-cycling exercises. Muscle biopsy samples were obtained from musculus deltoideus (m. deltoideus) and m. vastus lateralis muscles. Fibre-type composition, enzyme activity and O(2) flux capacity of saponin-permeabilized muscle fibres were measured, the latter by high-resolution respirometry. During the graded exercise tests, peak fat oxidation during leg cycling and the relative workload at which it occurred (FatMax) were higher in PO and O than in C. During arm cranking, peak fat oxidation was higher in O than in C, and FatMax was higher in O than in PO and C. Similar fibre-type composition was found between groups. Plasma adiponectin was higher in PO than in C and O, and plasma leptin was higher in O than in PO and C. In O subjects, maximal fat oxidation during exercise and the eliciting relative exercise intensity are increased. This is associated with higher intramuscular triglyceride levels and higher resting non esterified fatty acid (NEFA) concentrations, but not with differences in fibre-type composition, mitochondrial function or muscle enzyme levels compared with Cs. In PO subjects, the changes in fat oxidation are preserved during leg, but not during arm, exercise.

Obesity and metabolic efficiency.

Obesity has a strong genetic component, which should be viewed as a predisposition only if certain environmental factors are present. Impaired regulation of both sides of the energy balance equation plays a role in the propensity to gain weight and develop obesity. Overeating may be induced in susceptible individuals by high dietary fat content, large portion sizes and low meal frequency. Increased metabolic efficiency in the form of a low resting metabolic rate has been identified in pre- and post-obese subjects, and the impact on total energy expenditure may be amplified by a low level of physical activity. A low thermic effect of food has been shown not to be a risk factor for weight gain, and post-obese subjects have a normal thermic effect of food. A genetically determined enhanced metabolic efficiency during overfeeding has been reported to contribute to fat gain. The heterogeneous nature of obesity indicates that different mechanisms, such as changes in the partitioning of fat (due to lipoprotein lipase activity, fat oxidative muscle enzymes) and carbohydrate, and an altered responsiveness of the sympathoadrenal system and thyroid hormones to a positive energy balance, seem to be involved.

Molecular mechanisms of diabetes reversibility after bariatric surgery

Insulin resistance is a strong biological marker of both obesity and type 2 diabetes. Abnormal fat deposition within skeletal muscle has been identified as a mechanism of obesity-associated insulin resistance. Biliopancreatic diversion (BPD), inducing a massive lipid malabsorption, leads to a reversion of type 2 diabetes. To elucidate the mechanisms of diabetes reversibility, the expression of genes involved in glucose and free fatty acids (FFAs) metabolism was investigated in skeletal muscle biopsies from obese, type 2 diabetic subjects. Peripheral insulin sensitivity and insulin secretion was also measured. Eight Caucasian obese diabetic patients (BMI 52.1+/-1.85 kg/m(2)) were studied before and 3 years after BPD. The mRNA levels were estimated by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), insulin sensitivity by the euglycemic-hyperinsulinemic clamp and insulin secretion using a model describing the relationship between insulin secretion and glucose concentration. Whole-body glucose uptake (M), normalized by fat-free mass, significantly increased in post-obese subjects (P<0.0001). Total insulin output decreased (P<0.05) in association with a significant improvement of beta-cells glucose sensitivity (P<0.05). mRNA levels of FABP3 (P<0.05), FACL (P<0.05), ACC2 (P<0.05), HKII (P<0.05) and PDK4 (P<0.05) were significantly decreased, while SREBP1c mRNA increased (P<0.05) after BPD. Reversibility of type 2 diabetes after BPD is dependent on the improvement of skeletal muscle insulin sensitivity, mediated by changes in the expression of genes regulating glucose and fatty acid metabolism in response to nutrient availability.

Effect of moderate cold exposure on 24-h energy expenditure: similar response in postobese and nonobese women.

Twenty-four-hour energy expenditure (EE) and substrate oxidation rates were measured two times in eight postobese women and eight matched controls. On one occasion the subjects were exposed to a room temperature of 16 degrees C, on the other to 24 degrees C. Cold exposure elicited a 2% increment in 24-h EE (P < 0.05), with similar response in the two groups. The slight increase in EE was entirely covered by an enhanced carbohydrate oxidation rate. Fasting plasma norepinephrine (NE) increased from 0.74 +/- 0.08 to 1.29 +/- 0.21 nmol/l under cold exposure (P < 0.05), with no group difference. The cold-induced increase in 24-h EE was positively correlated to the increase in NE concentration (r2 = 0.41, P = 0.01). Sleeping EE was found to be 5% lower in the postobese women than in the controls (P = 0.04). The postobese group also had higher 24-h nonprotein respiratory quotient than the control group (P = 0.04), which was due to a 26% lower lipid-to-carbohydrate oxidation ratio. The study demonstrates that the thermogenic response to cold is normal in women susceptible to obesity, but it supports previous reports of a slightly lower basal EE and lower lipid-to-carbohydrate oxidation ratio in postobese subjects.

Évaluation de l’activité physique habituelle des adolescents en surpoids ou obèses

To develop a simple, rapid, and unbiased test to assess usual physical activity in overweight adolescents during a routine medical consultation. Adolescents were selected. Their heart rate (HR) and blood pressure (BP) were measured at rest and when standing, before the beginning of the test. Subjects went up and down a 2-step apparatus during 4 minutes at a rate of 92 steps/min. HR was monitored. At the end of the test, the HR was noted and BP measured immediately. The effects of usual physical activity and gender on HR and BP were tested by ANOVA. In addition, an activity questionnaire was filled in by 43 subjects over 7 days and given to the doctor who completed the information during the visit and assessed usual physical activity. 56 adolescents of both sexes, aged 10-17 years (31 sedentary [S] overweight, and 25 active [A] post-obese subjects) underwent a step-test. The increase in HR during the test was significantly higher in S than in A subjects (66.2 +/- 2.3 vs 52.3 +/- 2.5 bpm, p < 0.001). However, the variations in BP did not supply reliable assessment of usual physical activity. The activity questionnaire had been filled in satisfactorily by 72% of subjects. In 95% of cases, the classification of subjects as S or A by the step-test agreed with the classification based on the questionnaire. The step-test provided the rapid and reliable assessment of usual physical activity of the children (from 6-7 years of age) in 95% of cases during a routine consultation (30 min), and the activity questionnaire enabled the doctor to check the conclusions of the step-test and recommend to the parents physical activities adapted to the physical capacities of their children.

Persistence of abnormal neural responses to a meal in postobese individuals.

To determine whether abnormal obese-like neural responses to a meal persist in postobese individuals, who achieved and maintained a normal body weight despite a past history of severe obesity. Cross-sectional study of the brain's response to tasting and consuming a satiating meal in 11 postobese (age: 40+/-6 y, body mass index (BMI): 23.6+/-1.9 kg/m(2)), 23 obese (age: 29+/-6 y, BMI: 39.6+/-3.8 kg/m(2)) and 21 lean (age: 33+/-9 y, BMI: 22.8+/-2.1 kg/m(2)) subjects. Regional cerebral blood flow (rCBF, a marker of neural activity) at baseline (after a 36-h fast), after tasting and after consuming a satiating liquid meal was assessed using positron emission tomography and state-dependent changes (taste-baseline; satiation-baseline), and compared across groups. Subjective ratings of hunger and fullness were measured by a visual analogue scale and body fatness by dual-energy X-ray absorptiometry. In response to tasting the liquid meal, changes in rCBF were different in the obese as compared to the lean individuals (P<0.05, corrected for multiple comparisons) in the middle insula (peak voxel, x=-41, y=1, z=8; Montreal Neurological Institute coordinates) and posterior cingulate cortex (peak voxel, x=17, y=-47, z=40). The middle insular cortex exhibited a similar increase of neural activity in the obese and postobese subjects, whereas in the lean subjects the regional activity did not change. In the posterior cingulate cortex, the changes in rCBF in the postobese subjects were not different from those in the other groups. In response to a satiating amount of the same liquid meal, changes in rCBF were different in the obese as compared to the lean individuals (P<0.05, corrected for multiple comparisons) in the posterior hippocampus (peak voxel, x=21, y=-45, x=4), posterior cingulate cortex (peak voxel, x=17, y=-47, z=40), and amygdala (peak voxel, x=27, y=1, z=-24). The posterior hippocampus exhibited a similar decrease of neural activity in the obese and postobese subjects, whereas in the lean subjects the regional activity increased. In the posterior cingulate cortex and amygdala, the changes in rCBF were not different between the postobese and lean individuals. None of the changes in neural activity were correlated with the age of the individuals, the subjective ratings of hunger and fullness, or the meal induced-changes in plasma glucose, insulin, or serum free fatty acids. Persistence of abnormal neural responses to a meal in the postobese individuals, a group at high risk for relapse, indicates that a predisposition to obesity may involve areas of the brain that control complex aspects of eating behavior including anticipation and reward, chemosensory perception, and autonomic control of digestion (insular cortex), as well as enteroception and learning/memory (hippocampus).

Effect of significant intermediate-term weight loss on serum leptin levels and body composition in severely obese subjects.

Leptin, produced by adipose tissue, signals body fat content to the hypothalamus. Serum leptin levels (SLL), elevated in obese humans, decrease with weight loss. This study investigated the reduction of SLL and fat mass following restrictive bariatric surgery. Obese subjects (body mass index [BMI] >35 kg/m2, n=154) undergoing gastric banding (weight-reduced subjects) were investigated for SLL and body composition before surgery and for 2 years after. Overweight subjects matched for fat mass and gender (fat mass-matched overweight controls, n=194) and subjects who had never been obese (normal weight controls, n=158) were studied for comparison. SLL were highest in weight-reduced subjects and decreased with weight loss (P <0.001), remaining elevated compared with normal weight controls (P <0.001) but lower than fat mass-matched overweight controls (women: P <0.04). At 2 years, SLL normalized for fat mass (allowing comparison between various levels of adiposity) were lower in weight-reduced subjects compared with fat mass-matched overweight controls (women: P =0.003), yet were similar for weight-reduced subjects at 2 years compared with normal weight controls despite 14 kg greater fat mass. Relative lean mass of extremities in weight-reduced subjects increased with weight loss (P <0.001). SLL decreased after considerable weight loss more than could be accounted for by fat mass or BMI reduction alone. This disproportionate decrease in SLL might point to a mechanism that evolved as adaptation to starvation during times of famine. Thus, post-obese subjects may be at risk of weight-regain due to disproportionately low SLL and increased appetite via the leptin-melanocortin pathway.

Decreased Uncoupling Protein Expression and Intramyocytic Triglyceride Depletion in Formerly Obese Subjects

To examine the muscular uncoupling protein expression 2 (UCP2) and UCP3 gene expression in morbid obese subjects before and after bariatric surgery [bilio-pancreatic diversion (BPD)]. Eleven obese subjects (BMI = 49 +/- 2 kg/m(2)) were studied before BPD and 24 months after BPD. Skeletal muscle UCP2 and UCP3 mRNA was measured using reverse transcriptase-competitive polymerase chain reaction and UCP3 protein by Western blotting. Intramyocytic triglycerides were quantified by high-performance liquid chromatography. Twenty-four-hour energy expenditure and respiratory quotient (RQ) were measured in a respiratory chamber. After BPD, the average weight loss was approximately 38%. Nonprotein RQ was increased in the postobese subjects (0.73 +/- 0.00 vs. 0.83 +/- 0.02, p < 0.001). The intramyocytic triglyceride level dropped (3.66 +/- 0.16 to 1.60 +/- 0.29 mg/100 mg of fresh tissue, p < 0.0001) after BPD. Expression of UCP2 and UCP3 mRNA was significantly reduced (from 35.9 +/- 6.1% to 18.6 +/- 4.5% of cyclophilin, p = 0.02; from 60.2 +/- 14.0% to 33.4 +/- 8.5%, p = 0.03; respectively). UCP3 protein content was also significantly reduced (272.19 +/- 84.13 vs. 175.78 +/- 60.31, AU, p = 0.04). A multiple regression analysis (R(2) = 0.90) showed that IMTG levels (p = 0.007) represented the most powerful independent variable for predicting UCP3 variation. The strong correlation of UCP expression and decrease in IMTG levels suggests that triglyceride content plays an even more important role in the regulation of UCP gene expression than the circulating levels of free fatty acids or the achieved degree of weight loss.

Lowering of Circulating Free-Fatty Acids Levels and Reduced Expression of Leptin in White Adipose Tissue in Postobesity Status

BackgroundOur aim was to investigate the regulation of the gene expression of leptin in subcutaneous adipose tissue biopsies in morbid obesity before and after biliopancreatic diversion (BPD).MethodsLongitudinal study in morbidly...

Sterol regulatory element binding proteins: relationship of adipose tissue gene expression with obesity in humans

Sterol regulatory element binding proteins (SREBPs) are transcription factors that are involved in adipogenesis and regulate the expression of genes controlling cholesterol and fatty acid biosynthesis. Animal experiments indicate that SREBP-1a, -1c, and -2 have distinct functions despite overlapping specificities for target genes. To study the possible relationships of SREBPs with obesity, we determined their expression levels in intra- and extraperitoneal adipose tissue samples of obese, post-obese and never-obese humans. We furthermore investigated possible associations of SREBP gene expression with mRNA levels of key enzymes of fatty acid and cholesterol biosynthesis. SREBP-1c was the most abundant SREBP mRNA isoform in human adipose tissue. mRNA levels of SREBP-1a and -1c correlated within tissues whereas no correlations were observed between SREBP-1a or -1c and SREBP-2 mRNA abundance. SREBP-1c and -2 mRNA levels were significantly lower in obese than in never-obese and post-obese subjects. SREBP-1c, but not -1a or -2 gene expression was associated with fatty acid synthase and acetyl-CoA carboxylase α gene expression in the intraperitoneal adipose tissue of obese humans. Our results suggest that common mechanisms are involved in the regulation of SREBP-1a and -1c expression in human adipose tissues and imply distinct functions of SREBP isoforms in the regulation of lipid and cholesterol biosynthesis. The reduction in SREBP-1c and -2 mRNA expression in obese humans and their upregulation after weight loss provides new insight into the relationship of these transcription factors with obesity in humans.

Enhanced dietary fat clearance in postobese women

The objective of this study was to examine the postprandial response to an exogenous fat source in eight weight-stable postobese subjects (2;-3 years after gastric bypass) and eight matched control women, using a stable isotope, [13C]oleate. After a high fat breakfast meal (1,062 cal, 67% fat), [13C]oleate in triglyceride (TG)-rich lipoproteins (Sf >400 and Sf 20;-400) and nonesterified fatty acids (NEFA), and 13C in breath CO2, were monitored over 8 h. There were no differences in resting energy expenditure, thermic effect of food, carbohydrate/fat oxidation ratio, breath 13CO2 enrichment, or fecal fat content between postobese and control subjects. Postprandially, there was no difference in S(f) 20;-400 TG or NEFA, but postobese subjects had lower Sf >400 incremental area under the curve (AUC) (- 33%, P < 0.0025) and glucose [P < 0.01 by repeated measures analysis of variance (RM ANOVA)]. Postprandial 13C in Sf >400 TG returned to fasting levels 4 h earlier in postobese subjects and was lower than in control subjects at 4 and 6 h (P < 0.05 by RM ANOVA). The greatest difference was in the [13C]NEFA profiles. In control subjects [13C]NEFA increased markedly over 8 h; postobese subject [13C]NEFA remained close to fasting nonenriched values, and was strikingly lower than in control subjects (72% lower by AUC, P < 0.0001 by RM ANOVA). Finally, postobese subjects tended to have lower postprandial insulin (P < 0.01, 4 h), lower postprandial acylation-stimulating protein, and lower fasting leptin (-46%, P < 0.02). This study demonstrates clear metabolic differences in exogenous dietary fat partitioning in postobese women. These findings are compatible with an increased efficiency of dietary fat storage and suggest one possible mechanism for promotion of weight regain in postobese individuals.

Relative overhydration of fat-free mass in postobese versus never-obese subjects.

Obese subjects who undergo gastrointestinal surgery for weight reduction have relatively greater loss of body cell mass (BCM) than of extracellular fluid. Although the mechanism is uncertain, an implication is that weight-reduced, surgically treated obese subjects are relatively overhydrated. The present investigation explored whether diet-treated postobese (PO) subjects also are relatively overhydrated. Ten PO participants were recruited over a two-year period and matched to never-obese (NO) people by age (+/- 4 years), weight (+/- 3 kg), height (+/- 5 cm), race, and gender. PO participants had lost > or = 18.5 kg and had maintained this loss for 2-16 years. Body density (Db), total body water (TBW), and bone mineral content (BMC) were measured by hydrodensitometry, tritium dilution, and dual-energy X-ray absorptiometry, respectively. Fat and fat-free mass (FFM) were derived using a four-compartment model. BCM was calculated from total body potassium (TBK) measured with a whole body counter. The results indicate that PO subjects were relatively overhydrated and had reduced BCM compared to NO subjects (p < 0.05). These observations are important for interpreting body weight, body composition, and metabolic data of obese subjects who lost weight and maintained their weight loss over the long term.

Low plasma leptin concentration and low rates of fat oxidation in weight-stable post-obese subjects.

A low resting metabolic rate for a given body size and composition, a low rate of fat oxidation, low levels of physical activity, and low plasma leptin concentrations are all risk factors for body weight gain. The aim of the present investigation was to compare resting metabolic rate (RMR), respiratory quotient (RQ), levels of physical activity, and plasma leptin concentrations in eight post-obese adults (2 males and 6 females; 48.9 +/- 12.2 years; body mass index [BMI]: 24.5 +/- 1.0 kg/m2; body fat 33 +/- 5%; mean +/- SD) who lost 27.1 +/- 21.3 kg (16 to 79 kg) and had maintained this weight loss for > or =2 months (2 to 9 months) to eight age- and BMI-matched control never-obese subjects (1 male and 7 females; 49.1 +/- 5.2 years; BMI 24.4 +/- 1.0 kg/m2; body fat 33 +/- 7%). Following 3 days of weight maintenance diet (50% carbohydrate and 30% fat), RMR and RQ were measured after a 10-hour fast using indirect calorimetry and plasma leptin concentrations were measured using radioimmunoassay. Levels of physical activity were estimated using an accelerometer over a 48-hour period in free living conditions. After adjustment for fat mass and fat-free mass, post-obese subjects had, compared with controls, similar levels of physical activity (4185 +/- 205 vs. 4295 +/- 204 counts) and similar RMR (1383 +/- 268 vs. 1430 +/- 104 kcal/day) but higher RQ (0.86 +/- 0.04 vs. 0.81 +/- 0.03, p < 0.05). Leptin concentration correlated positively with percent body fat (r = 0.57, p < 0.05) and, after adjusting for fat mass and fat-free mass, was lower in post-obese than in control subjects (4.5 +/- 2.1 vs. 11.6 +/- 7.9 ng/mL, p < 0.05). The low fat oxidation and low plasma leptin concentrations observed in post-obese individuals may, in part, explain their propensity to relapse.

Body Composition and Energy Expenditure after Weight Loss Following Bariatric Surgery

Objectives: To assess the effectiveness of biliopancreatic diversion (BPD) in the treatment of morbid obesity and to evaluate how the procedure affects body weight.Subjects: Fourteen morbidly obese subjects studied before and 30 months after BPD and fifteen healthy volunteers matched for age, sex and height (controls).Methods: Comparison of the following parameters were made in the study groups before surgery and 30 months after BPD and with those of the controls group: fat mass, fat-free mass, non-protein substrate oxidation, basal metabolic rate, plasma glucose, insulin and free fatty acid concentrations.Results: Obese subjects lost 60.38±10.71 kg of weight during 18 months following surgery and then remained stable for another 12 months, when this study was performed. Weight loss was substantially due to a loss of fat mass (FM: 60.13±13.01 kg before and 19.02±8.61 kg after BPD; p<0.001). FM were not statistically different between post-obese subjects and controls; however, post-obese patients retained significantly more fat free mass (FFM) than controls. Subsequently, basal metabolic rates of post-obese subjects were higher than those of the control group (p<0.05). Fasting non-protein respiratory quotient (npRQ) was significantly lower before BPD than 30 months after the surgery (0.798±0.04 vs. 0.90±0.048, p<0.001), suggesting that, while obese, patients oxidized more lipids than carbohydrates. Moreover, fasting and two-hour plasma glucose and insulin concentrations decreased significantly after BPD to values comparable to those of the control group.Conclusion: Weight loss in obese patients after BPD is mainly due to lipid malabsorption, but increased energy expenditure associated with retaining a high FFM in physically active post-obese subjects may also play a role, enabling them to maintain long-term reduced body weights.

Leptin is influenced both by predisposition to obesity and diet composition.

(1) To investigate whether plasma leptin concentrations differ between subjects with and without the genetic predisposistion to obesity, and (2) to investigate the effect of dietary manipulations on plasma leptin in these subjects. Fasting and postprandial plasma leptin concentrations were measured before and after 14 days' ad libitum intake of a fat-rich (FAT), starch-rich (STARCH) or sucrose-rich (SUCROSE) diet. On day 15 ad libitum breakfast and lunch were given and blood sampled regularly until 6 p.m. Eight normal-weight, post-obese women and 10 matched controls (body mass index, 23.5+/-0.5 and 22.9 +/- 0.3 kg/m2). Leptin, glucose, insulin, appetite ratings, dietary intake, body weight and composition. Fasting leptin concentration on day 1 or 15 did not differ between post-obese and controls. However, after meal intake leptin increased in post-obese compared with controls on all three diets. In both groups fasting and postprandial leptin concentrations were greater after SUCROSE compared with FAT and STARCH. A larger postprandial leptin concentration was observed in post-obese subjects than in controls. This may be related to greater insulin sensitivity in adipose tissue in the post-obese. Furthermore, increased leptin concentrations were found after a sucrose-rich diet in both groups, possibly related to larger postprandial insulin peaks on this diet. Both contentions should, however, be validated by further studies.

Leptin, peroxisome proliferator-activated receptor-gamma, and CCAAT/enhancer binding protein-alpha mRNA expression in adipose tissue of humans and their relation to cardiovascular risk factors.

Obesity is a prevalent disorder that increases the risk for premature cardiovascular disease. The adipose tissue itself plays an active role in the regulation of fuel metabolism and energy homeostasis by expressing a number of regulatory genes, such as leptin, peroxisome proliferator-activated receptor-gamma (PPARgamma), and CCAAT/enhancer binding protein-alpha (C/EBPalpha). To study the in vivo relationships among these genes and their associations with cardiovascular risk factors, plasma levels of leptin, lipids, apolipoproteins (apo), insulin, and glucose were measured in 216 obese, 165 nonobese, and 36 weight-losing postobese subjects. mRNA expression of leptin, PPARgamma, and C/EBPalpha in the extraperitoneal and intraperitoneal adipose tissue was quantified in subsets of subjects. In obese individuals, plasma leptin was associated with apoA-I (r=0.2346, P<0.001) and insulin (r=0.2125, P<0.002). Leptin and C/EBPalpha mRNA expression in extraperitoneal and intraperitoneal adipose tissue of obese patients was higher than in the respective tissues of nonobese or postobese subjects. No significant differences among the study groups were found for PPARgamma mRNA expression. Leptin, PPARgamma, and C/EBPalpha mRNA levels correlated with each other in the intraperitoneal and extraperitoneal fat of obese subjects, but multivariate analysis revealed that only C/EBPalpha was a predictor of leptin expression in extraperitoneal tissue (partial r=0.6096, P<0.001). Intraperitoneal PPARgamma expression was inversely related to fasting insulin (r=-0.2888, P<0.017) and a fasting insulin resistance index (r=-0.2814, P<0.021) in obese subjects. In postobese patients, intraperitoneal PPARgamma expression was associated with plasma HDL cholesterol (r=0.5695, P<0.018) and apoA-I (r=0.6216, P<0.008) but was inversely related to LDL cholesterol (r=-0.5101, P<0.03) and apoB (r=-0.6331, P<0.007). These findings suggest a relationship between plasma leptin and HDL metabolism as well as adipose-tissue site-dependent associations among leptin, C/EBP-alpha, and PPAR-gamma mRNA expression. Furthermore, our results suggest that C/EBP-alpha enhances leptin expression in vivo and that PPARgamma mRNA expression is inversely associated with cardiovascular risk factors.

Exercise training and substrate utilisation in obesity.

Together with diet and behavioural modification, regular exercise is one of the key components of programs for the treatment of obesity. It appears to be one of the major factors determining the long-term success of weight loss programs. One of the mechanisms that may underlie this and other beneficial effects of regular exercise is the effect of exercise training on substrate utilisation. Exercise training increases fat oxidation in lean subjects. The capacity to mobilise and oxidise fat has been shown to be impaired in obese and post-obese subjects. Thus, an increase in the capacity for fat oxidation may help to maintain fat and energy balance at a lower fat mass in individuals with a predisposition for obesity. However, in view of the impaired fat oxidation in obese and post-obese individuals the question arises whether exercise training also increases fat oxidation in the obese. Few studies have addressed this question and have investigated the effect of exercise training on substrate utilisation in obesity. Addition of an exercise training program has been shown to prevent the reduction of basal fat oxidation that is associated with diet-induced weight loss in two studies. No effect of additional exercise training on substrate oxidation during exercise was found. In post-obese subjects exercise training caused no change in 24 h substrate oxidation in one study and increased carbohydrate, rather than fat oxidation in another. In obese subjects neither low (40% maximal aerobic fitness (VO2max)) nor high (70% VO2max) intensity training was found to affect resting substrate oxidation. During exercise fractional fat oxidation was increased after low, but not after high intensity training. The question, whether exercise training increases fat oxidation in obese and post-obese as in lean subjects therefore cannot be answered conclusively at this point in time and requires further study. The role of exercise intensity and type of exercise needs to be studied as well.

Body image and body weight in obese patients.

To evaluate the influence of body weight on body image. The study was carried out in severely obese patients and in postobese subjects, having attained and maintaining a normal or nearly normal weight following biliopancreatic diversion; body image was assessed by self-report questionnaires. The obese patients' scores were different from those of postobese subjects. In postobese individuals with adult-onset obesity, body image was very similar to that of controls, whilst in those with early-onset obesity it was abnormal. In the adult-onset obese patients, since the weight normalization causes a sharp improvement of body image, its alterations could be accounted for by a body shape far different from that socially acceptable. In the early-onset obese patients, being the postoperative findings similar to those of the obese patients and different from those of never-obese controls, the body image disparagement might reflect inner feelings, independent of body weight.