Long-term Regulation Of Body Weight Research Articles

Fetuin-B, a potential link of liver-adipose tissue cross talk during diet-induced weight loss\u2013weight maintenance

Background/objectivesNumerous hepatokines are involved in inter-organ cross talk regulating tissue-specific insulin sensitivity. Adipose tissue lipolysis represents a crucial element of adipose insulin sensitivity and is substantially involved in long-term body weight regulation after dietary weight loss. Thus, we aimed to analyze the impact of the hepatokine Fetuin-B in the context of weight loss induced short- and long-term modulation of adipose insulin sensitivity.Subjects/methods143 subjects (age > 18; BMI ≥ 27 kg/m2) were analyzed before (T-3) and after (T0) a standardized 12-week dietary weight reduction program. Afterward, subjects were randomized to a 12-month lifestyle intervention or a control group. After 12 months (T12) no further intervention was performed until 6 months later (T18) (Maintain-Adults trial). Tissue-specific insulin sensitivity was estimated by HOMA-IR (predominantly liver), ISIClamp (predominantly skeletal muscle), and free fatty acid suppression during hyperinsulinemic-euglycemic clamp (FFASupp) (predominantly adipose tissue). Fetuin-B was measured at all concomitant time points.ResultsCirculating Fetuin-B levels correlated significantly with estimates of obesity, hepatic steatosis as well as HOMA-IR, ISIClamp, FFASupp at baseline. Fetuin-B decreased during dietary weight loss (4.2 (3.5–4.9) vs. 3.8 (3.2–4.6) µg/ml; p = 2.1 × 10−5). This change was associated with concomitant improvement of HOMA-IR (r = 0.222; p = 0.008) and FFASupp (r = −0.210; p = 0.013), suggesting a particular relationship to hepatic and adipose tissue insulin sensitivity. Weight loss induced improvements of insulin resistance were almost completely preserved until months 12 and 18 and most interestingly, the short and long-term improvement of FFASupp was partially predicted by baseline level of Fetuin-B.ConclusionsOur data suggest that Fetuin-B might be a potential mediator of liver-adipose cross talk involved in short- and long-term regulation of adipose insulin sensitivity, especially in the context of diet-induced weight changes.Trial registrationClinicalTrials.gov number: NCT00850629, https://clinicaltrials.gov/ct2/show/NCT00850629, date of registration: February 25, 2009.

Whole genome transcriptome analysis of the stomach resected in human vertical sleeve gastrectomy: cutting more than calories.

Vertical sleeve gastrectomy (VSG) is a surgical weight loss procedure that resects 80% of the stomach, creating a tube linking the esophagus to the duodenum. Because of the efficacy and relative simplicity of VSG, it is preferred in the United States, with VSG currently at >61% of bariatric surgeries performed. Surprisingly, there has never been a complete molecular characterization of the human stomach greater curvature's fundus and corpus. Here we compare and contrast the molecular makeup of these regions. We performed a prospective cohort study to obtain gastric tissue samples from patients undergoing elective VSG. Paired fundus and corpus samples were obtained. Whole genome transcriptome analysis was performed by RNA sequencing (N = 10), with key findings validated by qPCR (N = 24). Participants were primarily female (95.8%) and White (79.15%). Mean body mass index, body weight, and age were 46.1 kg/m2, 121.6 kg, and 43.29 yr, respectively. Overall, 432 gene transcripts were significantly different between the fundus and the corpus (P < 0.05). A significant correlation was found between the RNA sequencing dataset and qPCR validation, demonstrating robust gene expression differences between the fundus and the corpus. Significant genes included progastricsin, acidic chitinase, and gastokine 1 and 2 in both the fundus and the corpus. Of the very highly expressed genes in both regions, 87% were present in both the stomach's fundus and corpus, indicating substantial overlap. Despite significant overlap in the greater curvature gene signature, regional differences exist within the fundus and the corpus. Given that the mechanism of VSG is partly unresolved, the potential that the resected tissue may express genes that influence long-term body weight regulation is unknown and could influence VSG outcomes.

Polyunsaturated fatty acids as modulators of fat mass and lean mass in human body composition regulation and cardiometabolic health.

It is now recognized that the amount and type of dietary fat consumed play an important role in metabolic health. In humans, high intake of polyunsaturated fatty acids (PUFAs) has been associated with reductions in cardiovascular disease risk, improvements in glucose homeostasis, and changes in body composition that involve reductions in central adiposity and, more recently, increases in lean body mass. There is also emerging evidence, which suggests that high intakes of the plant-based essential fatty acids (ePUFAs)-n-6 linoleic acid (LA) and n-3 α-linolenic acid (ALA)-have a greater impact on body composition (fat mass and lean mass) and on glucose homeostasis than the marine-derived long-chain n-3 PUFA-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In addition, high intake of both ePUFAs (LA and ALA) may also have anti-inflammatory effects in humans. The purpose of this review is to highlight the emerging evidence, from both epidemiological prospective studies and clinical intervention trials, of a role for PUFA, in particular ePUFA, in the long-term regulation of body weight and body composition, and their impact on cardiometabolic health. It also discusses current notions about the mechanisms by which PUFAs modulate fat mass and lean mass through altered control of energy intake, thermogenesis, or lean-fat partitioning.

Thyroxine Treatment During the Perinatal Stage Prevents the Alterations in the ObRb-STAT3 Leptin Signaling Pathway Caused by Congenital Hypothyroidism.

Thyroid hormone deficiency during crucial stages of development causes congenital hypothyroidism. This syndrome alters hypothalamic pathways involved in long-term bodyweight regulation as ObRb-STAT3 leptin signaling pathway, which is associated with metabolic syndrome. This study aimed to determine if thyroxine treatment during pregnancy and lactation in hypothyroid mothers avoids, in the congenital hypothyroid offspring, the alterations in metabolic programming related to metabolic syndrome and the ObRb-STAT3 leptin signaling pathway in hypothalamus. Twenty-four virgin female Wistar rats were divided into euthyroid, hypothyroid, and hypothyroid with thyroxine treatment (20 μg/kg/day T4 since pregnancy until lactation). The bodyweight and energy intake, insulin resistance, glucose tolerance, metabolic and hormonal parameters were determined in offspring at 28 weeks after birth. Then, the rats were euthanized to obtain adipose tissue reserves and hypothalamus to measure the expression of ObRb, STAT3, pSTAT3, and SOCS3. Congenital hypothyroidism presented metabolic syndrome such as insulin resistance, glucose tolerance, dyslipidemias, an increase in cardiovascular risk (Castelli I males:166.67%, females: 173.56%; Castelli II males: 375.51%, females: 546.67%), and hypothalamic leptin resistance (SOCS3, Males: 10.96%, females: 25.85%). Meanwhile, the thyroxine treatment in the mothers during pregnancy and lactation prevents the metabolic disturbance. In conclusion, thyroxine treatment during the critical perinatal stage for metabolic programming prevents congenital hypothyroidism-caused metabolic syndrome and hypothalamic leptin resistance.

Genome sequencing and transcriptome analyses of the Siberian hamster hypothalamus identify mechanisms for seasonal energy balance

Synthesis of triiodothyronine (T3) in the hypothalamus induces marked seasonal neuromorphology changes across taxa. How species-specific responses to T3 signaling in the CNS drive annual changes in body weight and energy balance remains uncharacterized. These experiments sequenced and annotated the Siberian hamster (Phodopus sungorus) genome, a model organism for seasonal physiology research, to facilitate the dissection of T3-dependent molecular mechanisms that govern predictable, robust, and long-term changes in body weight. Examination of the Phodopus genome, in combination with transcriptome sequencing of the hamster diencephalon under winter and summer conditions, and in vivo-targeted expression analyses confirmed that proopiomelanocortin (pomc) is a primary genomic target for the long-term T3-dependent regulation of body weight. Further in silico analyses of pomc promoter sequences revealed that thyroid hormone receptor 1β-binding motif insertions have evolved in several genera of the Cricetidae family of rodents. Finally, experimental manipulation of food availability confirmed that hypothalamic pomc mRNA expression is dependent on longer-term photoperiod cues and is unresponsive to acute, short-term food availability. These observations suggest that species-specific responses to hypothalamic T3, driven in part by the receptor-binding motif insertions in some cricetid genomes, contribute critically to the long-term regulation of energy balance and the underlying physiological and behavioral adaptations associated with the seasonal organization of behavior.

Kisspeptin and RFRP3 modulate body mass in Phodopus sungorus via two different neuroendocrine pathways.

Many animals exhibit remarkable metabolic and reproductive adaptations to seasonal changes in their environment. When day length shortens, Djungarian hamsters (Phodopus sungorus) reduce their body weight and inhibit their reproductive activity, whereas the opposite occurs in springtime. These physiological adaptations are considered to depend on photoperiodic changes in hypothalamic genes encoding the peptides kisspeptin (Kp) and RFamide-related peptide 3 (RFRP3) for the control of reproduction, as well as pro-opiomelanocortin and somatostatin for metabolic regulation. The present study investigates the effect of Kp and RFRP3 on long-term body weight regulation, aiming to establish whether metabolic and reproductive hypothalamic networks may interact during adaptation to seasonal physiology. We found that chronic central administration of both Kp and RFRP3 in short photoperiod-adapted male Djungarian hamsters increased body weight, although via different pathways. The effect of Kp was dependent on testicular activity because castration prevented the body weight increase and was associated with an increase in pro-opiomelanocortin and neuropeptide Y expression. On the other hand, the orexigenic effect of RFRP3 was associated with an increase in circulating insulin and leptin levels, although it had no effect on any of the hypothalamic metabolic genes investigated, and did not change circulating levels of sex steroids. Notably, neither Kp, nor RFRP3 altered female hamster metabolic parameters. Thus, using a rodent model exhibiting seasonal changes in reproduction and metabolism, the present study demonstrates that, in addition to its role in the central control of reproduction, Kp also participates in body weight control in a sex-dependent manner via an anabolic action of testosterone. Conversely, RFRP3 affects body weight control in males mostly by acting on adiposity, with no overt effect on the reproductive system in both sexes.

The Value of Comparative Animal Research: Krogh's Principle Facilitates Scientific Discoveries.

Biomedical research is dominated by relatively few nonhuman animals to investigate healthy and disease conditions. Research has overrelied on these models due to their well-described genomes, the capability to control specific genes, and the high rate of reproduction. However, recent advances in large-scale molecular sequencing experiments have revealed, in some cases, the limited similarities in experimental outcomes observed in common rodents (i.e., mice) compared with humans. The value of more varied comparative animal models includes examples such as long-term body weight regulation in seasonally breeding hamsters as a means to help understand the obesity epidemic, vocal learning in songbirds to illuminate language acquisition and maintenance, and reproduction in cichlid fish to discover novel genes conserved in humans. Studying brain genes in prairie voles and cichlids advanced knowledge about social behavior. Taken together, experiments on diverse animal species highlight nontraditional systems for advancing our understanding of human health and well-being.

Central and peripheral leptin and agouti-related protein during and after pregnancy in relation to weight change.

To study changes of neuropeptides and adipokines in cerebrospinal fluid (CSF) and serum from pregnancy to postpregnancy in relation to weight changes, fat mass and glucose metabolism. With high postpartum weight retention being a risk factor in future pregnancies and of lifelong obesity, we evaluated neuropeptide and adipokine changes in women who either gained weight or were weight stable. Women were followed for 5±1years after pregnancy and divided into two groups, weight stable and weight gain, by weight change from start of pregnancy. Twenty-five women (BMI 27±5kg/m2 ) recruited at admission for elective caesarean section. CSF and serum levels of agouti-related protein (AgRP), leptin and insulin, and serum levels of adiponectin and soluble leptin receptor were measured during and after pregnancy. These measurements were further related to fat mass and insulin sensitivity (HOMA-IR). S-AgRP levels during pregnancy were lower in the weight stable group and a 1 unit increase in s-AgRP was associated with 24% higher odds of pertaining to the weight gain group. After pregnancy, s-AgRP increased in the weight stable group but decreased in the weight gain group. Decreased transport of leptin into CSF during pregnancy was reversed by an increased CSF:serum leptin ratio after pregnancy. In women who returned to their prepregnancy weight, serum adiponectin increased after pregnancy and correlated negatively with HOMA-IR. S-AgRP concentration in late pregnancy may be one factor predicting weight change after pregnancy, and circulating AgRP may be physiologically important in the long-term regulation of body weight.

Homeostatic and Circadian Control of Food Intake: Clinical Strategies to Prevent Overconsumption

The current environment has a strong impact on the rise in population body weight as it provides ample opportunity to consume food, often beyond one’s metabolic requirement. The homeostatic processes that regulate food intake are often overlooked or weakened in such an environment, particularly among susceptible individuals. Moreover, there is strong circadian control over food intake and the circadian system is tightly entwined in body weight regulation. Clinical nutritional and behavioral strategies can strengthen homeostatic signals of satiation and satiety and improve appetite control. Synchronizing the circadian system through exercise and regular sleeping and meal patterns may also enhance these signals. Together, these strategies can help reduce overeating episodes, particularly among susceptible individuals, and may play a role in better long-term body weight regulation.

Leptin overexpression in VTA trans-activates the hypothalamus whereas prolonged leptin action in either region cross-desensitizes

High-fat feeding or CNS leptin overexpression in chow-fed rats results in a region-specific cellular leptin resistance in medial basal hypothalamic regions and the ventral tegmental area (VTA). The present investigation examined the effects of targeted chronic leptin overexpression in the VTA as compared with the medial basal hypothalamus on long-term body weight homeostasis. The study also examined if this targeted intervention conserves regional leptin sensitivity or results in localized leptin resistance. Cellular leptin resistance was assessed by leptin-stimulated phosphorylation of signal transducers and activators of transcription 3 (STAT3). Tyrosine hydroxylase was measured in hypothalamus and VTA along with brown adipose tissue uncoupling protein 1. Leptin overexpression in VTA tempered HF-induced obesity, but to a slightly lesser extent than that with leptin overexpression in the hypothalamus. Moreover, the overexpression of leptin in the VTA stimulated cellular STAT3 phosphorylation in several regions of the medial basal hypothalamus, whereas verexpression in the hypothalamus did not activate STAT3 signaling in the VTA. This unidirectional trans-stimulation did not appear to involve migration of either the vector or the gene product. Long-term leptin overexpression in either the medial basal hypothalamus or VTA caused desensitization of leptin signaling in the treated region and cross-desensitization of leptin signaling in the untreated region. These results demonstrate a role of leptin receptors in the VTA in long-term body weight regulation, but the trans-activation of the hypothalamus following VTA leptin stimulation suggests that an integrative response involving both brain regions may account for the observed physiological outcomes.

Decreased ghrelin levels: the cause of obesity and weight regain?

Ghrelin is a circulating orexigenic hormone which is implicated in both the short-term control of food intake at single meals and in long-term body weight regulation. Due to the potent orexigenic a...

Past dieting is related to rigid control and disinhibition in adolescents from the Québec Family Study

Eating behaviour traits of rigid control and disinhibition have been associated with body weight in both adults and adolescents. Moreover, adults reporting a dieting history have increased levels of unhealthy eating behaviours. Against this background, the present study aimed to examine the relationship between dieting history and eating behaviour traits in adolescents. For the purpose of this research, a total of sixty adolescents (aged 15 (sem 2·4) years) from the Québec Family Study completed the Three-Factor Eating Questionnaire (TFEQ) and a questionnaire regarding eating habits. Self-reported current and past dieting were analysed against eating behaviour traits measured by the TFEQ, including all subscales. As the results revealed, few adolescents reported currently dieting (n 3). Adolescents who reported a dieting history (23·3%) were older (16·9 v. 14·4 years, P<0·001), were more likely to be female (78·6 v. 41·3%, P<0·05) but did not have a significantly higher BMI z-score (1·5 v. 0·9, P=0·10), although they were more likely to be either overweight or obese (P<0·01). After correcting for sex, BMI and age, adolescents who reported a dieting history had higher levels of rigid control and disinhibition (P<0·05-0·0001) than those reporting no dieting history. A greater proportion of adolescents characterised by high rigid control and high disinhibition were past dieters, compared to those characterised by low levels of both behaviour traits (53 v. 4%). The study arrived at the following conclusions: as observed in adults, adolescents with a history of dieting present unfavourable eating behaviour traits. These behavioural traits may represent an additional challenge to the long-term regulation of body weight.

Ghrelin and feeding behaviour in preterm infants

The importance of early life events in the development of metabolic diseases is well recognized. Early postnatal environment, including nutrition, is key to future health, and this is particularly true for preterm infants. It is important that these infants receive sufficient nutrients to prevent growth restriction and promote neurodevelopment, while minimizing predisposition to metabolic diseases later in life. Feeding habits are the fundamental elements of nutrition and are influenced by many factors, including personal and familial habits, socioeconomic status, and cultural environment. In the last decades, there has been an important scientific interest toward the comprehension of the molecular and neural mechanisms regulating appetite. In these networks, act many peptide hormones produced in brain or gut, among which ghrelin is important because of its action in the short-term regulation of food intake and the long-term regulation of body weight. Ghrelin stimulates appetite and plays a role in regulating feeding behaviour. Ghrelin levels vary from fetal life through to early adulthood, with the highest levels observed in the very early years. Cord ghrelin levels have been evaluated in term and preterm newborns and high ghrelin levels have been observed in small-for-gestational age newborns and in newborns with intrauterine growth restriction. Moreover, ghrelin has been detected in term and preterm human breast milk, suggesting that it may play a role in the development of neuroendocrine pathways regulating appetite and energy homeostasis in early life. However, more research is required to better define ghrelin's role in breast milk and on feeding behaviour.

Histaminergic regulation of seasonal metabolic rhythms in Siberian hamsters

We investigated whether histaminergic tone contributes to the seasonal catabolic state in Siberian hamsters by determining the effect of ablation of histaminergic neurons on food intake, metabolic rate and body weight. A ribosomal toxin (saporin) conjugated to orexin-B was infused into the ventral tuberomammillary region of the hypothalamus, since most histaminergic neurons express orexin receptors. This caused not only 75–80% loss of histaminergic neurons in the posterior hypothalamus, but also some loss of other orexin-receptor expressing cells e.g. MCH neurons. In the long-day anabolic state, lesions produced a transient post-surgical decrease in body weight, but the hamsters recovered and maintained constant body weight, whereas weight gradually increased in sham-lesioned hamsters. VO2 in the dark phase was significantly higher in the lesioned hamsters compared to shams, and locomotor activity also tended to be higher. In a second study in short days, sham-treated hamsters showed the expected seasonal decrease in body weight, but weight remained constant in the lesioned hamsters, as in the long-day study. Lesioned hamsters consumed more during the early dark phase and less during the light phase due to an increase in the frequency of meals during the dark and decreased meal size during the light, and their cumulative food intake in their home cages was greater than in the control hamsters. In summary, ablation of orexin-responsive cells in the posterior hypothalamus blocks the short-day induced decline in body weight by preventing seasonal hypophagia, evidence consistent with the hypothesis that central histaminergic mechanisms contribute to long-term regulation of body weight.

Review article: the role of gastric motility in the control of food intake

From a classical point of view, gastric motility acts to clear the stomach between meals, whereas postprandial motility acts to provide a reservoir for food, mixing and grinding the food and to assure a controlled flow of food to the intestines. To summarise findings that support the role of gastric motility as a central mediator of hunger, satiation and satiety. A literature review using the search terms 'satiety', 'satiation' and 'food intake' was combined with specific terms corresponding to the sequence of events during and after food intake. During food intake, when gastric emptying of especially solids is limited, gastric distension and gastric accommodation play an important function in the regulation of satiation. After food intake, when the stomach gradually empties, the role of gastric distension in the determination of appetite decreases and the focus will shift to gastric emptying and intestinal exposure of the nutrients. Finally, we have discussed the role of the empty stomach and the migrating motor complex in the regulation of hunger signals. Our findings indicate that gastric motility is a key mediator of hunger, satiation and satiety. More specifically, gastric accommodation and gastric emptying play important roles in the regulation of gastric (dis)tension and intestinal exposure of nutrients and hence control satiation and satiety. Correlations between gastric accommodation, gastric emptying and body weight indicate that gastric motility can also play a role in the long-term regulation of body weight.

Ghrelin and PYY3−36 in gastrectomized and vagotomized patients: relations with appetite, energy intake and resting energy expenditure

Reduced food intake, appetite loss and alteration of ghrelin and PYY(3-36) secretion have been suggested to have a function in the loss of body weight commonly observed after gastrectomy. The objective of this study was to investigate the circulating concentrations of ghrelin and PYY(3-36) and their relationships with food intake, appetite and resting energy expenditure (REE) after gastrectomy plus vagotomy. Seven patients with total gastrectomy (TG), 14 with partial gastrectomy (PG) and 10 healthy controls were studied. Habitual food intake and REE was assessed; fasting and postprandial plasma total ghrelin, PYY(3-36) concentrations and appetite ratings were determined after ingestion of a liquid test meal. Differently from PG and controls, fasting ghrelin correlated with REE, and a higher energy intake was observed in the TG group. Fasting plasma ghrelin concentrations were lower in TG compared with controls, and no ghrelin response to the meal was observed in either PG or TG. Fasting plasma PYY(3-36) concentrations were not different among the groups. There was an early and exaggerated postprandial rise in PYY(3-36) levels in both PG and TG groups, but not in controls. No effect of ghrelin or PYY(3-36) concentrations was observed on hunger, prospective consumption or fullness ratings. Total ghrelin and PYY(3-36) do not seem to be involved with appetite or energy intake regulation after gastrectomy plus vagotomy. Ghrelin secreted by sources other than stomach is likely to have a function in the long-term regulation of body weight after TG.

Age-related alterations in the long-term regulation of food intake and body weight

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The Effect of Physical Activity on Body Weight

There is evidence to support that low fitness and physical activity, excess body weight, and excess abdominal fatness are associated with increased health risk. Moreover, evidence exists to support that sufficient levels of physical activity can significantly improve body weight, fatness, and health risk. Physical activity has been shown to have a modest effect on body weight that is typically <3% of initial body weight, but has an additive effect when combined with dietary restriction. Moreover, physical activity has been shown to be an important behavioral factor for enhancing long-term weight loss and minimizing weight regain; however, this may require relatively high doses of physical activity that approach 300 min/week. Physical activity may concurrently reduce abdominal adiposity, and which may serve as a pathway by which there is also an improvement in health-related risk factors for various chronic diseases. There are important areas of research that require further investigation, with particular need to further examine the dose of physical activity that significantly affects these health outcomes. Moreover, there is a need for improved interventions to promote the adoption and long-term maintenance of physical activity, which can lead to improved weight control, abdominal adiposity, and chronic disease risk factors. Future research is also needed to understand the physiological/metabolic pathways and mechanisms that explain the influence of physical activity on long-term regulation of body weight.

Total and Acylated Ghrelin Levels in Type 2 Diabetic Patients: Similar Levels Observed after Treatment with Metformin, Pioglitazone or Diet Therapy

Ghrelin, a potent gut-brain orexigenic peptide, has a role in stimulation of food intake and long-term regulation of body weight. Metformin and pioglitazone treatment have different effects on body weight. This discrepancy might be related with the effect of these two drugs on plasma ghrelin levels. We investigated the effect of these two drugs on post-prandial acylated and total ghrelin levels in patients with type 2 diabetes. Eleven patients treated with diet, 12 patients treated with 850 mg/day metformin monotherapy and 12 patients treated with 30 mg/day pioglitazone monotherapy for at least 6 months were enrolled in the study. Plasma acylated and total ghrelin levels were investigated at baseline and at the 60 (th), 120 (th), 180 (th), 240 (th) minutes after a mixed meal test. There were no differences between groups in any of baseline metabolic and anthropometric parameters, including acylated and total ghrelin levels. Acylated and total ghrelin concentrations were suppressed similarly after food consumption, and we could not determine any significant difference between the groups at any time interval. A prolonged postprandial suppression of acylated ghrelin concentrations was observed in the pioglitazone treatment group compared with baseline values. In conclusion, total and acylated ghrelin levels after a mixed meal test were similar in type 2 diabetic patients treated with metformin, pioglitazone or diet therapy alone. These results suggest that changes in body weight during metformin and pioglitazone treatment are not associated with plasma ghrelin levels.

Fasting and postprandial relationships among plasma leptin, ghrelin, and insulin in prepubertal obese children

Leptin is involved in the long-term regulation of body weight and dietary intake, while ghrelin plays an essential role in appetite control. High levels of leptin have been associated with adiposity and the suppression of ghrelin levels with increased dietary intake. To evaluate fasting and postprandial concentrations of plasma leptin and ghrelin after intake of a standardised breakfast and to study the relationship of these hormones with adiposity and insulin resistance in obese prepubertal children. 34 obese and 20 normal-weight prepubertal children aged 6-12 years were selected. Plasma leptin and ghrelin were measured by ELISA and radioimmunoassay, respectively. The general linear model of variance, principal-component factor, and Pearson's analyses correlation were performed. Baseline and postprandial leptin levels were higher in obese versus normal-weight children. In obese, ghrelin showed an altered pattern during the postprandial period, recovering to baseline levels at 3h after the intake. Insulin resistance was associated with leptin and independently with ghrelin. The association of ghrelin with insulin resistance provides further evidence on the regulation of ghrelin in glucose homeostasis in childhood obesity at the prepubertal age. Changes in ghrelin after dietary intake may be related to an earlier recovery of appetite in prepubertal obese children.