Effects of weight loss in metabolically healthy obese subjects after laparoscopic adjustable gastric banding and hypocaloric diet

Weight loss in metabolically healthy obese (MHO) subjects may result in deterioration of cardio-metabolic risk profile. We analyzed the effects of weight loss induced by laparoscopic adjustable gastric banding (LAGB) on cardio-metabolic risk factors in MHO and insulin resistant obese (IRO) individuals. This study included 190 morbidly obese non-diabetic subjects. Obese individuals were stratified on the basis of their insulin sensitivity index (ISI), estimated from an OGTT, into MHO (ISI index in the upper quartile) and IRO (ISI in the three lower quartiles). Anthropometric and cardio-metabolic variables were measured at baseline and 6-months after LAGB. Six months after LAGB, anthropometric measures were significantly reduced in both MHO and IRO. Percent changes in body weight, BMI, and waist circumference did not differ between the two groups. Fasting glucose and insulin levels, triglycerides, AST, and ALT were significantly reduced, and HDL cholesterol significantly increased, in both MHO and IRO subjects with no differences in percent changes from baseline. Insulin sensitivity increased in both MHO and IRO group. Insulin secretion was significantly reduced in the IRO group only. However, the disposition index significantly increased in both MHO and IRO individuals with no differences in percent changes from baseline between the two groups. The change in insulin sensitivity correlated with the change in BMI (r = −0.43; P<0.0001). In conclusion, our findings reinforce the recommendation that weight loss in response to LAGB intervention should be considered an appropriate treatment option for morbidly obese individuals regardless of their metabolic status, i.e. MHO vs. IRO subjects.     

Restricted diet modifies carbohydrate metabolism in immature rats

The aim of the present work was to study the effect of a restricted diet on carbohydrate metabolism in submandibular glands of female prepuber rats and the influence of arachidonic acid derivatives. Rats of 21 days of age were divided into three groups. Group I: normally fed rats. Group II: restricted diet (50% of the normal food intake). Group III: normally restricted diet with re-feeding. The baseline concentration of tissue glycogen was significantly higher in Group II than in I or III and after 60 min of incubation in a glucose free medium all groups showed a glycogen drop. In addition, the glucose metabolism was increased in Group II. Cycloxigenase inhibitors failed to alter (14)CO(2) levels in Groups I and III. In Group II, indomethacin and acetylsalicylic acid inhibited glucose metabolism, which was reverted by PGE(2) addition. The exogenous arachidonic acid metabolism and different eicosanoids showed that restricted diet significantly increased the production of PGE(2) but diminished PGF(2)(alpha) production. Our results suggest that a restricted diet would lead to a new dynamic equilibrium of glucose homeostasis. Prostaglandins E(2) and F(2)(alpha) would participate by adapting the source of energy to tissue demands while maintaining the metabolic features that characterize puberty.     

Comparison of glucostatic parameters after hypocaloric diet or bariatric surgery and equivalent weight loss

Weight-loss independent mechanisms may play an important role in the improvement of glucose homeostasis after Roux-en-Y gastric bypass (RYGB). The objective of this analysis was to determine whether RYGB causes greater improvement in glucostatic parameters as compared with laparoscopic adjustable gastric banding (LAGB) or low calorie diet (LCD) after equivalent weight loss and independent of enteral nutrient passage. Study 1 recruited participants without type 2 diabetes mellitus (T2DM) who underwent LAGB (n = 8) or RYGB (n = 9). Study 2 recruited subjects with T2DM who underwent LCD (n = 7) or RYGB (n = 7). Insulin-supplemented frequently-sampled intravenous glucose tolerance test (fsIVGTT) was performed before and after equivalent weight reduction. MINMOD analysis of insulin sensitivity (Si), acute insulin response to glucose (AIRg) and C-peptide (ACPRg) response to glucose, and insulin secretion normalized to the degree of insulin resistance (disposition index (DI)) were analyzed. Weight loss was comparable in all groups (7.8 ± 0.4%). In Study 1, significant improvement of Si, ACPRg, and DI were observed only after LAGB. In Study 2, Si, ACPRg, and plasma adiponectin increased significantly in the RYGB-DM group but not in LCD. DI improved in both T2DM groups, but the absolute increase was greater after RYGB (258.2 ± 86.6 vs. 55.9 ± 19.9; P < 0.05). Antidiabetic medications were discontinued after RYGB contrasting with 55% reduction in the number of medications after LCD. No intervention affected fasting glucagon-like peptide (GLP)-1, peptide YY (PYY) or ghrelin levels. In conclusion, RYGB produced greater improvement in Si and DI compared with diet at equivalent weight loss in T2DM subjects. Such a beneficial effect was not observed in nondiabetic subjects at this early time-point.     

High-fat diet overrules the effects of training on fiber-specific intramyocellular lipid utilization during exercise

In this study, we compared the effects of endurance training in the fasted state (F) vs. the fed state [ample carbohydrate intake (CHO)] on exercise-induced intramyocellular lipid (IMCL) and glycogen utilization during a 6-wk period of a hypercaloric (～+30% kcal/day) fat-rich diet (HFD; 50% of kcal). Healthy male volunteers (18-25 yrs) received a HFD in conjunction with endurance training (four times, 60-90 min/wk) either in F (n = 10) or with CHO before and during exercise sessions (n = 10). The control group (n = 7) received a HFD without training and increased body weight by ～3 kg (P < 0.001). Before and after a HFD, the subjects performed a 2-h constant-load bicycle exercise test in F at ～70% maximal oxygen uptake rate. A HFD, both in the absence (F) or presence (CHO) of training, elevated basal IMCL content by ～50% in type I and by ～75% in type IIa fibers (P < 0.05). Independent of training in F or CHO, a HFD, as such, stimulated exercise-induced net IMCL breakdown by approximately twofold in type I and by approximately fourfold in type IIa fibers. Furthermore, exercise-induced net muscle glycogen breakdown was not significantly affected by a HFD. It is concluded that a HFD stimulates net IMCL degradation by increasing basal IMCL content during exercise in type I and especially IIa fibers. Furthermore, a hypercaloric HFD provides adequate amounts of carbohydrates to maintain high muscle glycogen content during training and does not impair exercise-induced muscle glycogen breakdown.     

Modulation of adipocytokines response and weight loss secondary to a hypocaloric diet in obese patients by -55CT polymorphism of UCP3 gene.

Decreased expression or function of UCP3 (uncoupling protein 3) could reduce energy expenditure and increase the storage of energy as fat. Some studies have pointed to a role of UCP3 in the regulation of whole body energy homeostasis, diet induced obesity, and regulation of lipids as metabolic substrates. The C/C genotype of a polymorphism in the UCP3 promoter (-55C-->T) is associated with an increased expression of UCP3 mRNA in muscle. The aim of our study was to investigate the influence of -55CT polymorphism of UCP3 gene on adipocytokines response and weight loss secondary to a hypocaloric diet in obese patients. A population of 107 obese (body mass index >30) nondiabetic outpatients was analyzed in a prospective way. Before and after three months of a hypocaloric diet, an indirect calorimetry, tetrapolar electrical bioimpedance, blood pressure, a serial assessment of nutritional intake with 3-day written food records, and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1520 kcal, 52% of carbohydrates, 25% of lipids and 23% of proteins). The exercise program consisted of aerobic exercise for at least 3 times per week (60 minutes each). The mean age was 49.5+/-34.5 years and the mean BMI 34.5+/-4.8, with 27 males (25.3%) and 80 females (74.7%). Ninety patients (25 males/65 females) (83.6%) had the genotype 55CC (wild group) and 17 patients (2 male/15 females) (16.4%) 55CT (mutant group). The percentage of responders (weight loss) was similar in both groups (wild group: 84.7% vs. mutant group: 81.8%). BMI, weight, fat mass, systolic blood pressure, LDL cholesterol, waist circumference, and waist-to-hip ratio decreased in the wild group and RMR and VO (2) were increased. In the mutant group, BMI and weight decreased. Leptin and IL-6 levels have a significant decrease in the wild group (9.6%: p<0.05) and (30.5%: p<0.05), respectively. Patients with -55CC genotype have a significant decrease in leptin, interleukin 6, BMI, weight, fat mass, systolic blood pressure, LDL cholesterol, waist circumference, waist-to-hip ratio weight, fat mass, and systolic blood pressure.     

Hyperleptinemia in obese adolescents deregulates neuropeptides during weight loss

Leptin has emerged over the past decade as a key hormone not only in energy balance regulation but also in neuroendocrine and inflammatory processes. The aim of the present study was to evaluate whether hyperleptinemia deregulates neuropeptides during weight loss. A total of 86 post-pubertal obese adolescents (with or without hyperleptinemia) participated in one year of interdisciplinary weight loss therapy (clinical, nutritional, psychological and exercise-related). Adipokine and neuropeptide concentrations were measured by ELISA, visceral fat was measured by ultrasound and body composition was measured by pletismography. The hyperleptinemic patients presented a lower alpha-MSH concentration and higher NPY/AgRP ratio while the adiponectin/leptin (A/L) ratio was lower compared with the non-hyperleptinemic group. After therapy, significant improvements in BM, BMI, body fat mass, visceral and subcutaneous fat, HOMA-IR, QUICKI, total cholesterol and triglycerides were observed in both groups. Indeed, we observed significant increases in adiponectin and A/L as well as reductions in leptin and NPY/AgRP ratio in the hyperleptinemic group. In the stepwise multiple linear regression analysis with leptin concentration as the dependent variable, α-MSH and body fat mass (%) were the independent predictors to explain leptin concentration. For the entire group, we found positive correlations between leptinemia and BMI and body fat mass (%) as well as a negative correlation with free fat mass (%) and alpha-MSH. Finally, we verified negative correlations between adiponectin/leptin ratio with total cholesterol and LDL-c, only in hyperleptinemic patients. In conclusion, the hyperleptinemia in obese adolescents deregulates neuropeptides during weight loss.     

Substrate utilization during acute exercise in obese Zucker rats

The purpose of the present study was to compare the carbohydrate use of insulin-resistant obese Zucker rats with that of their lean littermates during steady-state exercise. Obese and lean rats were randomly assigned to a sedentary group or to a run group in which rats ran at 72-73% of their maximal O2 consumption, with the duration of exercise set to require an energy expenditure of 2.1-2.2 kcal. During the run the respiratory exchange ratio was significantly higher in the obese than in the lean rats [0.94 +/- 0.01 (SE) and 0.86 +/- 0.01, respectively], which indicate that the obese rats required 54% more carbohydrate than the lean rats. Total muscle glycogen utilization in the soleus, plantaris, and red and white gastrocnemius was not different between groups. Obese rats had total liver glycogen values five times greater than those of lean rats (833.38 +/- 101.4 and 152.8 +/- 37.5 mg, respectively) and utilized twice as much liver glycogen as their lean littermates (193.5 and 90.4 mg, respectively). The obese rats exhibited higher blood glucose and insulin concentrations than the lean rats during the run. These findings indicate that, despite their characteristic insulin resistance, the obese Zucker rats had a greater dependency on carbohydrate as a substrate during exercise than their lean littermates and that the major source of this carbohydrate was liver glycogen.     

Antagonism of specific corticotropin-releasing factor receptor subtypes selectively modifies weight loss in restrained rats

Rats exposed to 3 h of restraint stress on each of 3 days (RRS) lose weight on the days of RRS and gain weight at the same rate as controls after stress ends, but do not return to the weight of controls. RRS rats also show an exaggerated endocrine response to subsequent novel stressors. Studies described here tested the effects of corticotropin-releasing factor receptor (CRFR) antagonism on RRS-induced weight loss, hypophagia, and corticosterone release during mild stress in the postrestraint period. Weight loss was not prevented by either peripheral or third-ventricle administration of a CRFR1 antagonist, antalarmin, before each restraint. Antalarmin did, however, allow recovery of body weight in the poststress period. Third-ventricle administration of a CRFR2 antagonist, antisauvagine 30, had no effect in RRS rats but caused sustained weight loss in control animals. Surprisingly, third-ventricle administration of the nonselective CRFR antagonist, astressin, caused hypophagia and reversible weight loss in control rats. It had no effect in RRS rats. None of the antagonists modified the corticosterone response to RRS or to mild stress in the post-RRS period, but antalarmin suppressed corticosterone during the period of restraint in Control rats. These results suggest that CRFR1 activation is required for the initiation of events that lead to a prolonged down-regulation of body weight in RRS rats. The sustained reduction in body weight is independent of the severity of hypophagia on the days of restraint and of RRS-induced corticosterone release.     

Randomised comparison of diets for maintaining obese subjects' weight after major weight loss: ad lib,low fat,high carbohydrate diet v fixed energy intake.

OBJECTIVES: To compare importance of rate of initial weight loss for long term outcome in obese patients and to compare efficacy of two different weight maintenance programmes. DESIGN: Subjects were randomised to either rapid or slow initial weight loss. Completing patients were re-randomised to one year weight maintenance programme of ad lib diet or fixed energy intake diet. Patients were followed up one year later. SETTING: University research department in Copenhagen, Denmark. SUBJECTS: 43 (41 women) obese adults (body mass index 27-40) who were otherwise healthy living in or around Copenhagen. INTERVENTIONS: 8 weeks of low energy diet (2 MJ/day) or 17 weeks of conventional diet (5 MJ/day), both supported by an anorectic compound (ephedrine 20 mg and caffeine 200 mg thrice daily); one year weight maintenance programme of ad lib, low fat, high carbohydrate diet or fixed energy intake diet (< or = 7.8 MJ/day), both with reinforcement sessions 2-3 times monthly. MAIN OUTCOME MEASURES: Mean initial weight loss and proportion of patients maintaining a weight loss of > 5 kg at follow up. RESULTS: Mean initial weight loss was 12.6 kg (95% confidence interval 10.9 to 14.3 kg) in rapid weight loss group and 12.6 (9.9 to 15.3) kg in conventional diet group. Rate of initial weight loss had no effect on weight maintenance after 6 or 12 months of weight maintenance or at follow up. After weight maintenance programme, the ad lib group had maintained 13.2 (8.1 to 18.3) kg of the initial weight loss of 13.5 (11.4 to 15.5) kg, and the fixed energy intake group had maintained 9.7 (6.1 to 13.3) kg of the initial 13.8 (11.8 to 15.7) kg weight loss (group difference 3.5 (-2.4 to 9.3) kg). Regained weight at follow up was greater in fixed energy intake group than in ad lib group (11.3 (7.1 to 15.5) kg v 5.4 (2.3 to 8.6) kg, group difference 5.9 (0.7 to 11.1) kg, P < 0.03). At follow up, 65% of ad lib group and 40% of fixed energy intake group had maintained a weight loss of > 5 kg (P < 0.07). CONCLUSION: Ad lib, low fat, high carbohydrate diet was superior to fixed energy intake for maintaining weight after a major weight loss. The rate of the initial weight loss did not influence long term outcome.     

A hypocaloric diet enriched in legumes specifically mitigates lipid peroxidation in obese subjects

Legume intake could specifically protect against lipid peroxidation in addition to the effects associated to weight loss when included in hypocaloric diets. Thus, 30 obese subjects (age: 36 +/- 8 years and BMI: 32.0 +/- 5.3 kg/m(2)) were nutritionally treated by a 8-week energy restriction ( - 30% energy expenditure) with a legume enriched diet (4 days/week servings, [image omitted] ) or without legumes (control diet (CD), [image omitted] ). Body weight, circulating cholesterol, oxidized LDL (ox-LDL), malondialdehyde (MDA) and urinary 8-isoprostane F(2alpha) (8-iso-PGF(2alpha)) were measured at baseline and at endpoint. After the nutritional intervention, all obese subjects lost weight, specially those individuals who followed the legumes-enriched diet as compared to the CD ( - 7.7 +/- 3 vs. - 5.3 +/- 2.7%; p = 0.023), which was accompanied by marked decreases in total cholesterol levels (p < 0.001) and statistically significant diet-related reductions on plasma ox-LDL, plasma MDA and urinary 8-iso-PGF(2alpha) output. Therefore, a balanced diet with moderate caloric restriction including 4 day/week legume servings empowered the oxidative stress improvement related to weight loss through a reduction in lipid peroxidation as compared to a control hypocaloric diet.     

Responses of gut microbiota to diet composition and weight loss in lean and obese mice

Maintenance of a reduced body weight is accompanied by a decrease in energy expenditure beyond that accounted for by reduced body mass and composition, as well as by an increased drive to eat. These effects appear to be due--in part--to reductions in circulating leptin concentrations due to loss of body fat. Gut microbiota have been implicated in the regulation of body weight. The effects of weight loss on qualitative aspects of gut microbiota have been studied in humans and mice, but these studies have been confounded by concurrent changes in diet composition, which influence microbial community composition. We studied the impact of 20% weight loss on the microbiota of diet-induced obese (DIO: 60% calories fat) mice on a high-fat diet (HFD). Weight-reduced DIO (DIO-WR) mice had the same body weight and composition as control (CON) ad-libitum (AL) fed mice being fed a control diet (10% calories fat), allowing a direct comparison of diet and weight-perturbation effects. Microbial community composition was assessed by pyrosequencing 16S rRNA genes derived from the ceca of sacrificed animals. There was a strong effect of diet composition on the diversity and composition of the microbiota. The relative abundance of specific members of the microbiota was correlated with circulating leptin concentrations and gene expression levels of inflammation markers in subcutaneous white adipose tissue in all mice. Together, these results suggest that both host adiposity and diet composition impact microbiota composition, possibly through leptin-mediated regulation of mucus production and/or inflammatory processes that alter the gut habitat.     

Metabolomics reveals determinants of weight loss during lifestyle intervention in obese children

The amount of weight loss in obese children during lifestyle intervention differs strongly between individuals. The metabolic processes underlying this variability are largely unknown. We hypothesize that metabolomics analyses of serum samples might help to identify metabolic predictors of weight loss. In this study, we investigated 80 obese children aged 6–15 years having completed the one-year lifestyle intervention program ‘Obeldicks’, 40 that achieved a substantial reduction of their body mass index standard deviation score (BMI-SDS) during this intervention (defined as BMI-SDS reduction ≥ 0.5), and 40 that did not improve their overweight status (BMI-SDS reduction < 0.1). Anthropometric and clinical parameters were measured and baseline fasting serum samples of all children were analyzed with a mass spectrometry-based metabolomics approach targeting 163 metabolites. Both univariate regression models and a multivariate least absolute shrinkage and selection operator (LASSO) approach identified lower serum concentrations of long-chain unsaturated phosphatidylcholines as well as smaller waist circumference as significant predictors of BMI-SDS reduction during intervention (p-values univariate models: 5.3E?03 to 1.0E?04). A permutation test showed that the LASSO model explained a significant part of BMI-SDS change (p = 4.6E?03). Our results suggest a role of phosphatidylcholine metabolism and abdominal obesity in body weight regulation. These findings might lead to a better understanding of the mechanisms behind the large inter-individual variation in response to lifestyle interventions, which is a prerequisite for the development of individualized intervention programs.     

Observational study of bone accretion during successful weight loss in obese adolescents

Objective: To assess bone mineral content (BMC) among obese adolescents who lose weight during a critical period for bone accretion. Methods and Procedures: Whole body, lumbar spine, lower, and upper limb BMC were measured in 62 obese adolescents who completed an intensive 12‐month weight loss trial. BMC was adjusted for height (z ‐scores) using data from a reference group of 66 adolescents (who were 18% overweight). Results: At baseline, the BMC of the obese group was higher than the reference group. During the 12‐month weight loss program, unadjusted BMC increased among the obese adolescents, despite successful weight loss. After adjustment for height, whole body BMC did not change significantly from baseline to 12 months (mean ± s.d.: 1.08 ± 0.67 to 1.06 ± 0.67, P = 0.7). Region‐specific BMC‐for‐height however decreased for the lower (1.07 ± 0.57 to 0.95 ± 0.59, P < 0.001) and upper (1.29 ± 0.56 to 1.18 ± 0.57, P = 0.01) limbs, but lumbar spine BMC‐for‐height increased (0.14 ± 1.06 to 0.40 ± 0.94, P < 0.001). These changes were largely and independently explained by changes in lean and fat mass. Discussion: This study confirms that obese adolescents have high BMC for height and suggests that, unlike adults, their BMC continues to increase during weight loss and remains higher than the BMC of a reference group. After adjustment for growth‐related changes, lower and upper limb BMC appears to decrease, while lumbar spine BMC appears to increase. These results suggest that to optimize the health benefits of weight loss among obese adolescents, their bone health should be better understood and addressed.     

High-fat diet offsets the long-lasting effects of running-wheel access on food intake and body weight in OLETF rats

We have previously demonstrated that running-wheel access normalizes the food intake and body weight of Otsuka Long-Evens Tokushima Fatty (OLETF) rats. Following 6 wk of running-wheel access beginning at 8 wk of age, the body weight of OLETF rats remains reduced, demonstrating a lasting effect on their phenotype. In contrast, access to a high-fat diet exacerbates the hyperphagia and obesity of OLETF rats. To determine whether diet modulates the long-term effects of exercise, we examined the effects of high-fat diet on food intake and body weight in OLETF rats that had prior access to running wheels for 4 wk. We found that 4 wk of running exercise significantly decreased food intake and body weight of OLETF rats. Consistent with prior results, 4 wk of exercise also produced long-lasting effects on food intake and body weight in OLETF rats fed a regular chow. When running wheels were relocked, OLETF rats stabilized at lower levels of body weight than sedentary OLETF rats. However, access to a high-fat diet offset these effects. When OLETF rats were switched to a high-fat diet following wheel relocking, they significantly increased food intake and body weight, so that they reached levels similar to those of sedentary OLETF rats fed a high-fat diet. Gene expression determination of hypothalamic neuropeptides revealed changes that appeared to be appropriate responses to the effects of diet and running exercise. Together, these results demonstrate that high-fat diet modulates the long-lasting effects of exercise on food intake and body weight in OLETF rats.     

Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats

Growing evidence suggests that oxytocin plays an important role in the regulation of energy balance and that central oxytocin administration induces weight loss in diet-induced obese (DIO) animals. To gain a better understanding of how oxytocin mediates these effects, we examined feeding and neuronal responses to oxytocin in animals rendered obese following exposure to either a high-fat (HFD) or low-fat diet (LFD). Our findings demonstrate that peripheral administration of oxytocin dose-dependently reduces food intake and body weight to a similar extent in rats maintained on either diet. Moreover, the effect of oxytocin to induce weight loss remained intact in leptin receptor-deficient Koletsky (fa(k)/fa(k)) rats relative to their lean littermates. To determine whether systemically administered oxytocin activates hindbrain areas that regulate meal size, we measured neuronal c-Fos induction in the nucleus of the solitary tract (NTS) and area postrema (AP). We observed a robust neuronal response to oxytocin in these hindbrain areas that was unexpectedly increased in rats rendered obese on a HFD relative to lean, LFD-fed controls. Finally, we report that repeated daily peripheral administration of oxytocin in DIO animals elicited a sustained reduction of food intake and body weight while preventing the reduction of energy expenditure characteristic of weight-reduced animals. These findings extend recent evidence suggesting that oxytocin circumvents leptin resistance and induces weight-loss in DIO animals through a mechanism involving activation of neurons in the NTS and AP, key hindbrain areas for processing satiety-related inputs.     

Preferential loss of body fat during starvation in dietary obese rats.

This study was undertaken to examine whether diet-induced obesity alters the amount and/or composition of weight lost during starvation. The amount and composition of weight lost during a 4-day period of starvation was determined before and at 17, 30 and 42 weeks after rats (350 g of body weight) were given a high fat diet (HFD). To control for effects of aging, a second group of rats, fed standard laboratory chow, was also subjected to similar periods of starvation. Although total weight loss during starvation was never greater for HFD rats than for chow-fed rats, the former group showed a clear patter of increasing loss of body fat and total energy and conservation of fat-free tissues with periods of starvation later in life. In addition, chow-fed rats showed substantial energy conservation during each period of starvation (i.e. they lost less energy each day than their pre-starvation energy requirements). In contrast, HFD rats demonstrated substantial energy conservation only at 17 weeks and not at 30 or 42 weeks; during the last period of starvation, their average daily loss of carcass energy exceeded their pre-starvation energy requirements. This suggests the increased fat mass of these rats may have led to increased fuel availability and to an increased metabolic rate during starvation. If these results are applicable to humans, the more obese subjects are likely to show greater total loss of energy than lean subjects, but show a lesser loss of lean body mass, at least initially. If protein requirements are reflected by the ability to mobilize protein during food restriction, protein requirements would be substantially lower in the dietary obese rats than in controls. In summary, diet-induced obesity leads to preferential loss of body fat and conservation of lean mass during starvation.     

Effects of diet macronutrient composition on body composition and fat distribution during weight maintenance and weight loss

Objective: Neurotransmitter systems participate in the regulation of food intake, and their activities are expected to influence eating behavior. Design and Methods: We investigated possible associations between body mass index (BMI) and central noradrenaline, serotonin, and dopamine activities, as reflected by the cerebrospinal fluid levels of their main metabolites methoxyhydroxyphenylglycol (MHPG), 5‐hydroxyindoleacetic acid (5‐HIAA), and homovanillic acid (HVA), respectively. We studied 192 subjects (111 males, 81 females) admitted to neurologic clinic for diagnostic investigations that included CSF analysis, and were found not to suffer from any major neurological disease. Subjects were categorized in three groups, namely in lower, in the two middle, and in upper BMI quartiles, the limits calculated separately for males and females. Results: No differences were found in MHPG levels between groups, while subjects in the upper BMI quartile showed significantly elevated levels of 5‐HIAA and HVA compared to the levels of subjects in lower and middle quartiles. Conclusions: The results provide evidence that in overweight subjects there are enhanced demands in serotoninergic and dopaminergic signaling for their reward system that may lead to increased motivation for food consumption. The implication of reward centers in eating behavior supports the hypothesis of common mechanisms in obesity and drug addiction.