Cardiac autonomic nervous system activity in obesity

The development of obesity is caused by a disturbance of energy balance, with energy intake exceeding energy expenditure. As the autonomic nervous system (ANS) has a role in the regulation of both these variables, it has become a major focus of investigation in the fields of obesity pathogenesis. The enhanced cardiac sympathetic drive shown in most of the studies in obese persons might be due to an increase in their levels of circulating insulin. The role of leptin needs further investigation with studies in humans. There is a blunted response of the cardiac sympathetic nervous system (SNS) activity in obese subjects after consumption of a carbohydrate-rich meal as well as after insulin administration. This might be due to insulin resistance. It is speculated that increased SNS activity in obesity may contribute to the development of hypertension in genetically susceptible individuals. It is also speculated that the increase in cardiac SNS activity under fasting conditions in obesity may be associated with high cardiovascular morbidity and mortality.     

Effects of manipulating sedentary behavior on physical activity and food intake

OBJECTIVES: Sedentary behaviors have been correlated with obesity. We investigated whether changes in sedentary behaviors relate to changes in energy intake and/or physical activity. STUDY DESIGN: Experimental within-subject crossover design in which children participated in three 3-week phases: baseline and increased and decreased targeted sedentary behaviors. PARTICIPANTS: Thirteen 8- to 12-year-old, nonobese children. MEASUREMENTS: Sedentary behaviors were measured through the use of daily activity logs, physical activity measured with accelerometers, and energy intake measured by means of repeated 24-hour recalls collected during each phase. Energy intake, energy expenditure, and energy balance per day were calculated. RESULTS: Children showed significant (P <.001) increases of 50% and decreases of 53% in targeted sedentary behaviors from baseline during the increase and decrease phases, respectively. There was a significant (P =.05) increase in energy balance per day (+350.7 kcal) when sedentary behaviors were increased, as the result of an increase in energy intake per day (+250.9 kcal) and a decrease in energy expenditure (-99.8 kcal). No significant changes in energy balance were observed when sedentary behaviors were decreased. CONCLUSIONS: Increasing sedentary behaviors had a greater influence on physical activity and energy intake than reducing sedentary behavior in nonobese youth. In some children, changes in sedentary behaviors may be important to modify energy balance and prevent obesity.     

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目的研究肥胖男性儿童的内分泌变化和瘦素(Leptin)对肥胖男性儿童的内分泌功能的作用。方法肥胖组为2000～2004年在哈尔滨市儿童医院门诊就医体重高于同年龄小儿标准体重20%的患儿90例,对照组为体检正常的男性儿童共90名,年龄在5～16岁。测定身高体重指数(BMI),Leptin、胰岛素、性腺系列、血脂系列,进行统计学分析。结果肥胖男性儿童与正常男性儿童比较,Leptin、胰岛素、雌二醇、总胆固醇、甘油三脂A/B、低密度脂蛋白、极低密度脂蛋白有显著的增加,睾酮、黄体生成素(LH)有显著的减少;肥胖男性儿童身高体重指数与Leptin、胰岛素、黄体酮、催乳素、载脂蛋白A、A/B之间有显著的负相关,与雌二醇、载脂蛋白B、极低密度脂蛋白之间有显著的正相关。结论Leptin可作为评价肥胖男性儿童内分泌功能的一项指标,Leptin与胰岛素、皮质醇、性激素等可能存在相互作用,对机体发育、能量代谢、应激反应等方面有所影响。     

运动、医务监督综合处方对单纯性肥胖青少年女学生血瘦素、血脂、血糖、胰岛素的影响

目的观察有氧运动、医务监督综合减肥处方对单纯性肥胖青少年女学生血瘦素、血脂、血糖、胰岛素的影响。方法对单纯性肥胖青少年女学生采取有氧运动、合理饮食、心理矫正和医务监督等疗法,进行为期10个月减肥活动,测定试验前、中、后血瘦素及相关激素变化。结果单纯性肥胖青少年女学生血瘦素、胰岛素、血脂、血糖和胆固醇水平明显高于正常组,且瘦素水平与肥胖程度和胰岛素呈正相关,减肥后瘦素及相关激素水平明显下降(P均<0.05)。结论综合减肥处方能有效降低体质量,改善肥胖青少年女学生体内胰岛素和瘦素抵抗作用,从而起到调节异常内分泌代谢的作用。     

Insulin and human obesity

The prevalence of obesity among modern communities increases dramatically and trends to achieve the characteristics of an epidemic. Obesity is the result of a sedentary life style and increased food intake, which characterises western communities. Obesity is closely related to insulin resistance and hyperinsulinemia and the very frequent combination of obesity and NIDDM is characterised as "Diabesity". The behaviour of man in seeking food and the amount of food consumption is a complicated situation, which is regulated by the CNS and especially in the arcuate nucleus of the hypothalamus. A repertoire of neurohormonal actions, generated in peripheral tissues and integrated in the CNS, encompasses many peptides with orexigenic and anorexigenic actions. Two main hormones, insulin and leptin, accomplish the fine-tuning of these peptides action at the critical level of body weight and energy control. The high prevalence of insulin resistance and hyperinsulinemia in obesity indicates a causative relationship between these two situations. It seems likely that insulin resistance in muscle cells is the prime "defect" which renders individuals vulnerable to obesity. The high prevalence of insulin resistance, about 25%, among otherwise healthy subjects indicates that this genetically determined "defect" may be the result of an evolutionary selection which rendered mankind capable of surviving during long periods of famine, in his long journey from the hunter-gatherer period of his life to the present time of plenty.     

Energy balance, physical activity, and thermogenic effect of feeding in premature infants

In order to assess the contribution of the thermogenic effect of feeding and muscular activity to total energy expenditure, nine premature infants were studied for 2 consecutive days during which time repeated measurements of energy expenditure by indirect calorimetry were performed throughout the day, combined with a visual activity score based on body movement. The infants were growing at 16.6 +/- 4.0 g/kg/day (mean +/- SD) and received 110 +/- 8 kcal/kg/day metabolizable energy (milk formula) and 522 +/- 40 mgN/kg/day. Their total energy expenditure was 68 +/- 4 kcal/kg/day indicating that 41 +/- 7 kcal/kg/day was retained for growth. Based on the combination of energy + N balances it was estimated that 80% of the weight gain was fat-free tissue and 20% was fat tissue. The rate of energy expenditure measured minute-by-minute was significantly and linearly correlated with the activity score in both the premeal (r = 0.75;p less than 0.001) and the postmeal periods (r = 0.74; p less than 0.001) with no difference in the regression slope, but with a significant difference in intercept. In preset feeding schedules the latter allowed an estimation of the thermogenic effect without the confounding effect of activity. This was found to be 3.1 +/- 1.8% when expressed as a percentage of metabolizable energy intake. However when the "classical" approach was used as a comparison (integration of extra energy expenditure induced by the meal), the thermogenic effect was found to be greater, i.e. 9.5 +/- 3.8% of the meal's metabolizable energy, due to the superimposed effect of physical activity in the postprandial state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulin and insulin resistance index are not independent determinants for the variation in leptin in obese children and adolescents

Recent findings have questioned the independent influence of insulin on leptin. We studied whether insulin contributes to leptin in obese children, independent of confounding parameters, such as total adiposity, fasting insulin resistance index, and fat free mass. In 100 obese boys and 103 obese girls, blood levels of leptin, insulin, glucose, and triglycerides were determined. The fasting insulin resistance index (FIRI) was calculated, and body composition was assessed by means of impedance. Leptin and glucose were higher in girls, and all estimates of adiposity were significantly associated with leptin. However, when adjusted for adiposity, the relationship between insulin and leptin, and also between FIRI and leptin, remained significant in boys and girls (p<0.05). Although several regression models were tested, neither insulin nor FIRI were found to contribute significantly and independently to leptin. BMI together with triglycerides and FFM were the main determinants for the variation in leptin in boys (adj. R2=0.46, p<0.0001). In girls, BMI explained a great magnitude of the variation in leptin (adj. R2=0.60, p<0.0001). These findings indicate that in the state of childhood and adolescent obesity, total adiposity but not insulin or insulin resistance index is the main determinant for leptin. In contrast to obese girls, the fat free mass and triglycerides contribute significantly to the variation in leptin in obese boys. The biological significance for these findings should be elucidated in longitudinal studies.     

The emerging role of leptin in humans

Leptin is an adipocyte-secreted hormone which plays a key role in energy homeostasis. Recent advances in leptin physiology have revealed that the main role of this hormone in humans is to signal energy availability in energy-deficient states. Interventional studies in leptin deficient children and observational studies in normal girls and boys support a role for leptin as a permissive factor for the initiation of puberty in children. Moreover, recent "proof of concept" studies involving leptin administration to humans further support its critical role in regulating energy homeostasis, neuroendocrine and immune function as well as insulin resistance in states of energy/caloric deprivation. Leptin's potential role in the therapy of several disease states, including hypothalamic amenorrhea, anorexia nervosa and syndromes of insulin resistance is under intensive investigation.     

Time course and determinants of leptin decline during weight loss in obese boys and girls.

OBJECTIVE: To investigate whether changes in leptin concentrations during weight loss can be explained by gender, puberty, baseline adiposity and changes in adiposity, body composition, rate of weight loss, physical activity and insulin concentrations. DESIGN: A longitudinal study with 9 repeated measures during a 12-week weight loss programme. SUBJECTS: Fifty-three boys and 62 girls (7.9-15.2 years) with body mass index (BMI) standard deviation scores (SDS) of median 2.78 and 2.70, respectively. MEASUREMENTS: Height, weight, fat mass percentage assessed by bioimpedance, Tanner stages, testicular size, physical activity scores, blood leptin (ng/ml) and insulin concentrations (pmol/l) were measured at baseline, and except for Tanner stage and testicular size, repeated regularly during the programme. RESULTS: The weight loss was accompanied by a steep decline in leptin concentrations during the first 10-11 days, followed by a less steep decline until day 82. Leptin declined to 39% in boys and 51% in girls of the level that was expected given the relationship at baseline between leptin and BMI SDS, and the BMI SDS changes during weight loss. The biphasic leptin decline was independent of gender, puberty, baseline adiposity or concomitant changes in BMI SDS, fat mass percentage, rate of weight loss, physical activity scores or insulin concentrations. CONCLUSION: The biphasic leptin decline, which exceeded the level expected, was independent of puberty, baseline adiposity and changes in adiposity, body composition, rate of weight loss, physical activity scores and insulin concentrations. The dissociation of the leptin-weight relationship during weight loss may contribute to the general leptin variability in obese subjects.     

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目的观察单纯性肥胖儿童和健康正常体重儿童血清脑源性神经营养因子(BDNF)质量浓度的差异,探讨BDNF与儿童肥胖及瘦素抵抗、胰岛素抵抗的关系。方法南京军区福州总医院儿科等于2004年5月至2005年5月应用酶联免疫法检测单纯性肥胖儿童(37例)和健康儿童(31例)血清BDNF质量浓度与胰岛素(INS)浓度,应用放射免疫法检测血清瘦素(LEP)质量浓度。比较两组儿童血清BDNF、INS、LEP的差异,分析血清BDNF质量浓度与血清LEP质量浓度和INS浓度的关系。结果(1)两组儿童的体重指数(BMI)、BDNF、INS及LEP均差异显著(BMI:F=175·05,P<0·01;BDNF:F=12·35,P<0·01;INS:F=21·71,P<0·01;LEP:F=48·89,P<0·01),肥胖组BMI、INS及LEP均明显高于健康组,而肥胖组BDNF明显低于健康组。(2)影响LEP的因素依次为BMI、丙氨酸转氨酶(ALT)、BDNF(R2=0·5946,F=0·31,P<0·01);影响INS的因素依次为BMI、BDNF(R2=0·2647,F=11·34,P<0·01)。去除BMI、ALT影响后,BDNF与LEP、INS负相关(BDNF与LEP:r=-0·2455,P<0·05;BDNF与INS:r=-0·2878,P<0·05)。结论(1)肥胖儿童血清BDNF缺乏,未发现“BDNF抵抗”的特点。(2)学龄前儿童血清LEP、INS受BMI影响最大,还受血清BDNF影响。BDNF是二者独立的负相关因素。     

Energy expended playing video console games: an opportunity to increase children's physical activity?

This study sought to quantify the energy expenditure and physical activity associated with playing the "new generation" active and nonactive console-based video games in 21 children ages 10-14 years. Energy expenditure (kcal) derived from oxygen consumption (VO2) was continuously assessed while children played nonactive and active console video games. Physical activity was assessed continuously using the Actigraph accelerometer. Significant (p < .001) increases from baseline were found for energy expenditure (129-400%), heart rate (43-84%), and activity counts (122-1288 versus 0-23) when playing the active console video games. Playing active console video games over short periods of time is similar in intensity to light to moderate traditional physical activities such as walking, skipping, and jogging.     

Tangled relationship between insulin resistance and microalbuminuria in children with obesity

Childhood obesity represents a complex disease with a well-known cardiometabolic burden including fatty liver, type 2 diabetes, metabolic syndrome, and cardiovascular disease. From a pathogenic point of view, insulin resistance (IR) represents the key factor underlying the spectrum of these obesity consequences. As observed in adults, recent data supported the occurrence of microalbuminuria (MA) as marker of early kidney dysfunction and its potential link with cardiometabolic factors also in children with obesity. In fact, a well-documented pathophysiological hypothesis both in adults and children supported an intimate correlation with the major feature of obesity such as IR through the influence of insulin on renal hemodynamics. Based on the clinical and prognostic relevance of this relationship in daily practice (including an increased risk of chronic kidney disease development overtime), more scientific attention needs to be paid to the evaluation of early kidney damage in children with obesity. In this paper, we attempt to address three debated questions regarding the intriguing liaison between IR and MA in children with obesity: (1) What is the prevalence of pediatric MA? (2) What is the state of art of MA in children with obesity? and (3) Is there a link between IR and MA in children with obesity?     

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目的观察二甲双胍治疗对高胰岛素血症肥胖患儿血清脂源性激素脂联素、抵抗素、瘦素水平的影响。方法2004-01—2005-02将武汉市儿童医院和同济医院54例高胰岛素血症肥胖患儿分为轻、中度肥胖组及重度肥胖组,均以二甲双胍治疗12周,测量治疗前后体重、空腹血糖、空腹胰岛素及脂源性激素脂联素、瘦素、抵抗素的变化。结果治疗前轻、中度肥胖组和重度肥胖组高胰岛素血症患儿空腹血糖水平与健康对照组比较差异无显著性(P>0.05),血清胰岛素、瘦素、抵抗素及胰岛素抵抗指数(HOMA-IR)均高于健康对照组(P<0.01),脂联素水平明显低于健康对照组(P<0.01)。二甲双胍治疗12周后与治疗前相比,血清胰岛素水平、胰岛素抵抗指数明显降低(P<0.01),轻、中度肥胖组及重度肥胖组血清瘦素水平分别由治疗前的(24.3±1.8)μg/L、(30.2±5.1)μg/L降低为治疗后的(19.6±6.3)μg/L、(24.7±5.3)μg/L,差异有统计学意义;抵抗素水平分别由治疗前的(16.5±6.0)μg/L、(22.3±5.2)μg/L升高为(22.0±5.1)μg/L、(30.6±11.7)μg/L,差异有统计学意义;轻、中度肥胖组和重度肥胖组血清脂联素水平治疗前分别为(8.4±3.2)mg/L、(6.5±1.2)mg/L,治疗后分别为(8.9±2.3)mg/L、(7.03±3.0)mg/L,治疗前后相比,P>0.05。体重指数(BMI)下降,但差异无显著性。结论二甲双胍能显著改善肥胖患儿胰岛素抵抗。降低血清瘦素水平可能是其改善胰岛素抵抗机制之一,但在对脂源性激素脂联素、抵抗素水平的改善上,有其局限性。     

The neuroendocrinology of childhood obesity

The regulation of energy balance is enormously complex, with numerous genetic, hormonal, neural and behavioral, and societal influences. Although the current epidemic of obesity clearly has its underpinnings in the changes in culture during the past half-century (see other articles in this issue), the role of the neuroendocrine system in the genesis of obesity, as described in this article, is physiologically and therapeutically unavoidable. An understanding of this system has suggested organic causes (and therapies) for some rare and not-so-rare forms of obesity. With so many inputs, it is not far-fetched to assume that dysfunction of other parts of this feedback system will be found to explain other forms of obesity in the future. What does this mean for obese children entering the pediatrician's office? Fortunately or unfortunately, diet and exercise are the mainstays of obesity therapy for children and adults. Most diet-exercise programs result in an acute 11-kg weight loss in adults; the question is whether it can be sustained without significant long-term behavioral modification. For instance, the European Sibutramine Trial of Obesity Reduction and Maintenance trial showed that 42% of treated subjects drop out; of those remaining, 77% of subjects lost more than 5% of initial body weight, but only 43% of those maintained more than 80% of this over 2 years. Could there be an organic component in those who do not respond? Of course, obesity pharmacotherapies sometimes have beneficial acute effects, but these drugs work for only as long as they are consumed; discontinuation tends to result in a "rebound" weight gain, suggesting that the cause of the obesity is still present. Furthermore, in 2001, there are no obesity drugs approved for children. A useful guiding principle is that children deserve at the minimum an initial medical evaluation, including birth weight, medical history, family history, dietary evaluation, and exercise assessment. Perhaps the most important feature that can distinguish "organic" from "behavioral" weight gain in childhood is the age of the "adiposity rebound." The Centers for Disease Control and Prevention now supplies BMI charts for boys and girls at www.cdc.gov/growthcharts. Plotting of the BMI versus age allows pediatricians to determine the age at which the BMI starts to increase (mean, 5.5 years). The earlier the adiposity rebound, the more likely the child will be obese as an adult, and the more likely that an organic cause can be determined. In such patients, thyroid levels and fasting insulin and leptin levels should be measured. An initial attempt at diet and exercise is essential; patients who do not respond with BMI stabilization should be investigated for a more ominous cause of their obesity. As the nosology of obesity improves, pediatricians will be able to increase the diagnostic efficiency and therapeutic success of this unfortunate, debilitating, and expensive epidemic.     

Leptin and metabolic hormones in preterm newborns

AIM: To investigate the inter-relation between leptin and other metabolic hormones in preterm and term infants and to explore whether a functional "adipoinsular axis" might exist in preterm newborns. METHODS: A total of 140 preterm and term newborns were prospectively recruited and categorised according to gestation length. Blood samples were taken at 24 hours (day 1), and on day 4-5 of life. RESULTS: Serum leptin, cortisol, free thyroxine, and plasma ACTH on day 1 were significantly higher in term than in preterm infants. The relation between serum leptin and gestation followed a non-linear pattern; the slope of the curve began to increase steeply between 33 and 35 weeks gestation. Serum leptin on day 1 was significantly associated with serum insulin, insulin:glucose ratio, and plasma ACTH in infants less than 34 weeks gestation; serum leptin on day 1 and day 4-5 were significantly correlated with insulin:glucose ratio in infants 34 or more weeks gestation. Significant changes in the pattern of metabolic hormones were observed in the first week of life. Serum insulin and plasma glucose were significantly increased between day 1 and day 4-5; serum leptin was significantly decreased. CONCLUSIONS: The circulating leptin concentration increases markedly after 34 weeks gestation and bears a close temporal relation with the exponential accumulation of body fat mass during that period. The inter-relation between serum leptin and insulin or insulin:glucose ratio before and after 34 weeks gestation indicates that the "adipoinsular axis" is likely to be functional in early (<34 weeks gestation) intrauterine life. The rapid decline in the circulating concentrations of leptin after birth may be of physiological advantage to preterm and term newborns by limiting their body energy expenditure and conserving nutritional reverses for subsequent growth and development.     

Leptin receptor gene Gln223Arg polymorphism is not associated with obesity and metabolic syndrome in Turkish children

The aim of the study was to investigate the relationship between leptin receptor gene (LEPR) Gln223Arg polymorphism and obesity in Turkish children. Ninety-two obese and 99 lean children (between 5-15 years) were included in the study. Twenty-three of the obese children were diagnosed with metabolic syndrome. Blood samples were collected for morning fasting blood glucose, insulin, leptin, and lipid level measurements. LEPR Gln223Arg polymorphism was analyzed by restriction fragment length polymorphism. Significant differences were observed in anthropometric measurements, fasting blood glucose, insulin, leptin, and lipid levels between obese and lean children. Serum leptin levels were markedly higher in obese children. No significant association was noted between Gln223Arg polymorphism and serum leptin, insulin and lipid levels. There were no differences in the genotype frequencies or allele distribution for Gln223Arg polymorphism among obese, obese with metabolic syndrome and lean children. Our findings suggest that there is no association between Gln223Arg polymorphism and obesity in Turkish children.     

The role of leptin, soluble leptin receptor, resistin, and insulin secretory dynamics in the pathogenesis of hypothalamic obesity in children

Introduction  In this study, we have investigated the role of leptin, soluble leptin receptor(sOb-R), resistin, and insulin secretory dynamics in the development of hypothalamic obesity. Materials and methods  Children who had hypothalamo-pituitary tumor were divided into two groups. First group included obese-overweight (hypothalamic obese = HOB group, n = 23) and second group included non-obese children (hypothalamic non-obese = HNOB group, n = 16). Exogenously obese-overweight children (OB group, n = 22) were included as controls. Basal and second-hour serum glucose and insulin in oral glucose tolerance test (OGTT), basal serum leptin, sOb-R, resistin levels, and homeostasis model assessment (HOMA) indexes were compared between the groups. Results  Age, sex, and pubertal status were similar in study groups. Median and interquartile ranges of body mass index (BMI) z scores were similar in HOB and OB groups (2.0 (1.5–2.1) and 2.1 (1.8–2.3), respectively). Serum leptin levels corrected for BMI were highest and total leptin/sOb-R ratios (free leptin index (FLI)) tended to be higher in HOB than HNOB and OB groups, indicating leptin resistance (leptin/BMI, 4.0 (1.6–5.2), 1.5 (0.8–3.1), and 2.5 (1.8–3.5); FLI, 2.0 (0.8–3.5), 0.6 (0.3–1.2), and 1.5 (1–2.3) in HOB, HNOB, and OB groups; respectively). Serum resistin levels were similar in groups (2.6 (1.9–3.1), 2.8 (1.7–3.4), and 3.0 (2.2–3.5) ng/ml in HOB, HNOB, and OB groups, respectively). Basal serum glucose, basal and second-hour insulin levels in OGTT, and HOMA index were higher in OB group than the HOB and HNOB groups, indicating insulin resistance in simple obesity; however, increment of insulin to same glycemic load in OGTT was highest in the HOB group indicating insulin dysregulation (p < 0.05). Conclusion  Hypothalamic obesity seems to be related to both dysregulated afferent (leptin) and efferent (insulin) neural outputs through the autonomic nervous system resulting in energy storage as fat. This work has been presented in part in the free communication session of ESPE 2007 meeting (Helsinki-Finland, 2007).     

Obesity in children

The alarming increase in obesity in children has become a major health problem in the increased incidence of type 2 diabetes as well as other complications including cardiovascular diseases, hepatic disorders, skeletal abnormalities, malignancies and in particular psychological disorders. Mechanisms of appetite and energy metabolism are mediated through hormones leptin and ghrelin, and neuropeptide-Y neurons as well as genetic factors. Control of obesity is largely through appetite control and physical exercise.