Impact of leptin and leptin‐receptor gene polymorphisms on serum lipids in Japanese obese children

Aim: Leptin is one of the factors affecting serum lipid profile. We investigated the association between serum lipids and leptin/leptin receptor (LEPR) gene polymorphisms in obese Japanese children. Methods: One hundred and thirty‐six obese children (99 males and 37 females, relative weight over than 20%) from 5 to 17 years of age were recruited from 10 institutes. Four known polymorphisms in leptin gene [(+19)A G, (?2548)G A, (?188)C A, (?633)C T] and four known polymorphisms in LEPR gene [Lys109Arg, Gln223Arg, Pro(G)1019Pro(A), Ser(T)343Ser(C)] were determined using polymerase chain reaction‐restriction fragment length polymorphism‐based analyses. Results: No associations were found between leptin gene polymorphisms and serum lipid profile. On the other hand, Lys109Arg and Ser343Ser polymorphism in LEPR gene, but not Gln223Arg or Pro1019Pro, had significant relationships with serum lipid profile; lower total and low‐density lipoprotein cholesterol levels in Arg109Arg homozygotes, and lower TG levels in Ser343Ser(C/C) homozygotes. In addition, LEPR gene also associated with relative weight; Arg109Arg homozygotes had higher relative weight and Ser343Ser(C/C) homozygotes had lower one. Conclusion: These results suggest that LEPR gene polymorphisms may partly contribute to serum lipid profile in obese children.     

经济不发达地区3～9岁儿童血清瘦素水平的变化

目的：了解经济不发达地区3～9岁儿童在营养状况相对较差时血清瘦素的水平及与相关生长发育指标的关系。方法：根据年龄和性别将研究对象分为<6岁女孩组(F36组)、<6岁男孩组(M36)、≥6岁女孩组(F69组)和≥6岁男孩组(M69组)共4组,调查其年龄、体重、身高并计算体重指数(BMI)、体脂百分量(BF%),使用双抗体夹心ELISA法检测瘦素浓度,比较各组间瘦素浓度的差异,同时在各组分析瘦素与各指标间的相关性。结果：①瘦素浓度在同性别比较中,差异无显著性(P>0.05),在同年龄比较中,女孩明显高于男孩(P<0.05);②无论是男孩还是女孩,在3～6岁儿童瘦素与BMI和BF无明显相关(P>0.05),而在6～9岁儿童瘦素浓度与BMI和BF显著相关(P<0.05)。结论：在经济不发达地区3～9岁儿童中瘦素存在性别差异,6～9岁儿童中瘦素与BMI和BF密切相关。     

瘦素受体基因20外显子突变对儿童脂质代谢影响的临床研究(英文)

目的：探讨瘦素受体基因(LEPR)第20外显子突变对脂质代谢的影响及肥胖儿童基因型与血脂的关系。方法：用聚合酶链反应限制性片段长度多态性(PCRRFLP)方法及聚丙烯酰胺凝胶电泳分析20外显子的基因突变频率,并测定单纯型肥胖儿童(102例)和健康儿童(81例)血清中甘油三脂(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)和低密度脂蛋白(LDL)水平。两组分别测量身高、体重,计算体重指数(BMI)及脂肪百分比。结果：肥胖儿童瘦素受体基因的20外显子经PCRRFLP及聚丙烯酰胺凝胶电泳分析,检测出3种基因型G/G,G/A和A/A型。肥胖儿童20外显子3057位G→A突变频率较健康儿童增高(P<0.05)。A/A基因型的肥胖儿童其血清TG(1.8±0.5mmol/Lvs1.0±0.4mmol/L,P<0.01)、BMI(33±5kg/m2vs25±4kg/m2,P<0.05)水平和脂肪百分比(30±8vs20±3,P<0.01)均明显高于G/G基因型者,而血清HDL水平则低于后者(1.08±0.23mmol/Lvs1.38±0.22mmol/L,P<0.01)。G/A型肥胖儿童,除其血清TG浓度高于G/G基因型者外(1.6±0.4mmol/Lvs1.0±0.4mmol/L,P<0.05),余各项指标均与另外两种基因型无明显差别。心电图检查显示部分A/A型血脂增高儿童有ST段和T波改变。结论：单纯型肥胖儿童瘦素受体基因第20外显子存在基因多态性,且该多态性明显影响肥胖儿童的脂质代谢及体脂分布。该研究为临床上开展对肥胖儿童的早期干预提供了理论依据。     

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.     

Serum leptin levels during childhood and adolescence: relationship with age, sex, adiposity and puberty

We studied serum leptin levels in 189 healthy children to evaluate related factors during childhood and adolescence. Leptin correlated with body mass index (BMI), triceps skinfold thickness (p<0.001) and body weight (p<0.01). Obese children and girls had higher leptin levels than non-obese children and boys, respectively (p<0.001). In girls, leptin correlated positively with age, skinfold thickness and BMI (p<0.001). In boys, leptin correlated negatively with age (p<0.001) and positively with skinfold thickness (p<0.05). Prepubertal boys had higher leptin levels than prepubertal girls and pubertal boys (p<0.05). Pubertal girls had higher leptin levels than prepubertal girls and pubertal boys (p<0.001). Leptin levels in girls were higher at Tanner stages 4 and 5 than at stage 1 (p<0.001). In conclusion, serum leptin levels are related with adiposity, have obviously age-related gender differences during childhood and adolescence, and may be involved in the maturation of reproductive capacity.     

No evidence for leptin as an independent associate of blood pressure in childhood and juvenile obesity

We studied whether leptin is an independent associate of blood pressure in obese children and adolescence. 102 obese children (48 girls, age: 11.6 +/- 2.22 yr; body mass index [BMI]: 27.45 +/- 4.4; blood pressure: 122.5 +/- 11.1/64.7 +/- 10.6 mm Hg and 54 boys, age: 11.5 +/- 2.4 yr; BMI: 27.6 +/- 4.4; blood pressure: 122.5 +/- 13.2/60.9 +/- 8.1 mm Hg [mean +/- SD]) were investigated. Serum leptin and insulin were measured by RIA; glucose was determined enzymatically. Fat mass (FM) was calculated by bioelectrical impedance. Leptin was higher in girls than in boys (p=0.018) but no significant gender differences were found with respect to indices of adiposity and systolic blood pressure (SBP). Children were divided into three groups, according to pubertal stage (Group 1: prepubertal, 32 boys/13 girls; Group 2: pubertal, 17 boys/25 girls; Group 3: late/postpubertal, 5 boys/10 girls). SBP and DBP correlated with body weight in the whole group (r=0.49, p<0.0001, and r=0.27, p=0.004). In Group 1, BMI showed the highest correlation to SBP; in Group 3 no indices of adiposity were related to SBP. In no case was leptin significantly associated with SBP after adjustment for adiposity. In Group 2, glucose was significantly associated with SBP after adjustment for body weight. In Group 3, however, no correlations were found between SBP, DBP and metabolic characteristics, perhaps due to small sample size. Stepwise multiple regression revealed that body weight and glucose contributed to the variation in SBP in the whole group (R2=0.31, p<0.0001). Insulin accounted for almost 8% of the variation in DBP (R2=0.08, p=0.0034). Body weight contributed significantly to SBP in boys (R2=0.39, p<0.0001) and girls (R2=0.24, p< 0.001). The results imply that body weight contributes independently to the variation in blood pressure. Glucose and insulin contribute to mean blood pressure to some extent, but our data do not support the assumption that leptin per se serves as an independent predictor of blood pressure in obese children and adolescents.     

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.     

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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。     

Serum leptin concentrations in relation to pubertal development

OBJECTIVES: The amount of adipose tissue influences pubertal development and fertility in girls. A candidate for mediating this is the hormone leptin, derived from adipocytes. This work was carried out to determine whether the leptin concentration in serum is regulated during pubertal development. SUBJECTS AND METHODS: Serum concentrations of leptin were determined by radioimmunoassay in a sample of 252 healthy children representing all pubertal stages. RESULTS: Serum leptin concentrations correlated directly with age (r = 0.53), body mass index (BMI) (r = 0.71), and weight for height SD score (r = 0.44) in girls and with BMI (r = 0.33) and weight for height SD score in boys (r = 0.36). Leptin concentrations increased with pubertal development in girls, resulting in significantly higher concentrations at pubertal stages 4 and 5 than at the prepubertal stage, whereas there was no change in the boys. CONCLUSIONS: Serum leptin concentrations increased during pubertal development in the girls, but remained constant in the boys. Whether the increase in serum leptin concentrations in girls is of importance for, or a consequence of, pubertal development is still to be determined.     

Leptin profile in neonatal gonadotropin surge and relationship between leptin and body mass index in early infancy

AIM: This study was designed to investigate the longitudinal and dynamic profile of leptin and its relationship with sex hormones including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and testosterone (TTE) in neonatal 'minipuberty'. We also investigated the effects of leptin in the regulation of body weight gain and body mass index (BMI) in the first 3 months of life. METHODS: A longitudinal study was carried out in a cohort of 15 male and 15 female term infants during the first 3 months of life. Blood samples were collected in the morning from the infants on the 3rd, 15th, 30th, and 90th days of life. At each sample collection, anthropometric measurements were recorded. Serum leptin, LH, FSH, E2 (girls only) and TTE (boys only) concentrations were analyzed using standard biochemical methods. Association of leptin with weight gain, BMI, and these hormones during infancy was evaluated. RESULTS: Leptin levels increased significantly between the 3rd and 90th days of life in both boys and girls. BMI of both groups increased significantly from the 3rd to the 90th day. There was no significant difference in the leptin levels and leptin/BMI ratios of the two sexes at different time points. Leptin levels on the 30th and 90th days correlated significantly with BMI in both sexes. LH and FSH levels in both groups were found to be significantly higher on the 15th day of life. No correlation was observed between leptin and LH, FSH, E2 or TTE levels throughout the study. CONCLUSIONS: Leptin levels do not differ between the two sexes during early infancy and possibly there is no role for leptin in the surge of gonadotropins or sex steroids in neonatal minipuberty. The relationship between leptin and BMI could not be seen in the first postnatal days and the transient lack of the regulatory effect of BMI on leptin concentrations might reflect an adaptive resistance in the production of leptin to support catch-up growth after initial physiological weight loss in newborns.     

瘦素和脂联素在儿童肥胖相关性高血压发病中的作用

目的探讨瘦素和脂联素在儿童肥胖相关性高血压发病中的作用。方法基于北京市儿童青少年代谢综合征研究项目的现况调查结果，非随机选择3 502名6~18岁学龄儿童（其中男1 784名，女1 718名）为研究对象，按照超重（包括肥胖）和高血压状态将研究对象分为4组，正常体重正常血压组（对照组，1 497名）、正常体重高血压组（HBP组，125名）、超重但血压正常组（OB组，1 349名）和超重合并高血压组（OB+HBP组，531名）。通过比较4组人群血清瘦素和脂联素水平，以及瘦素和脂联素与血压之间的相关回归分析，探讨其与肥胖和血压之间的关系。结果超重肥胖人群BMI、血压、胰岛素和瘦素水平显著升高，脂联素水平降低。HBP组与对照组BMI、瘦素、脂联素水平差异无统计学意义。OB组和OB+HBP组与对照组比较，BMI、SBP、DBP、胰岛素和瘦素水平升高，脂联素水平降低，与HBP组比较仍可见BMI、胰岛素和瘦素水平升高，脂联素水平降低。与OB组比较，OB+HBP组BMI和胰岛素水平及男性的瘦素水平明显升高。血压与年龄、BMI、胰岛素、瘦素均呈显著正相关（r=0.260~0.643,P<0.01），与脂联素呈显著负相关（r=-0.171~-0.332, P<0.01）。但在调整胰岛素或BMI后，瘦素、脂联素与血压的相关性减弱或消失。结论 超重人群血压、胰岛素及瘦素水平均高于对照人群，脂联素水平低于对照人群。瘦素、脂联素可能通过肥胖或胰岛素抵抗与血压相关。     

No relationship between leptin and cortisol in obese children and adolescents

Recent findings have shown that leptin downregulates the steroid producing system in the adrenal. We studied the interactions of leptin, insulin and cortisol in obese children and adolescents at different stages of maturation. In 44 boys (age 11+/-3.1 yr, body mass index [BMI] 29+/-5.3 [mean +/- SD]) and 35 girls (age 11.4+/-2.6 yr, BMI 29+/-4.3), blood levels of leptin, insulin, cortisol, and glucose were determined. Fat mass (FM) was calculated by bioelectrical impedance. No significant differences were found between boys and girls with respect to humoral and anthropometric characteristics. When children were divided according to maturation stage (prepubertal, pubertal, and late/postpubertal) insulin was higher in the more mature groups (p<0.01) and leptin was higher in the pubertal group (p=0.03). In the prepubertal and pubertal groups, the expected positive relationship between adiposity and leptin was found although the magnitude of this association decreased with maturity. In none of the groups studied was cortisol significantly correlated to leptin. Insulin (p=0.03) and glucose (p=0.01) were positively associated with cortisol in the prepubertal group after adjustment for adiposity. However, in the pubertal group an inverse correlation was found between insulin and cortisol (p=0.03), and between insulin and glucose after control for adiposity. In the late/ postpubertal group, no significant correlations were found between estimates of adiposity and humoral parameters even after adjustment for gender. Stepwise multiple regression failed to detect a significant influence of cortisol to explain the variation in leptin, and vice versa. BMI contributed to the variation in leptin (adj. R2 =0.275, p<0.0001), and glucose added 5% to the variation in cortisol (p=0.03). The results do not confirm the inverse association between leptin and cortisol found in adults. Although BMI reflects levels of leptin, it is likely that several other factors in conjunction with fatness modulate the relationship with leptin. Whether leptin per se exerts an influence on the hypothalamic-adrenal-adipo axis remains to be investigated in longitudinal studies.     

Correlations between high level sport-climbing and the development of adolescents

Over the last years concerns have been raised about the health effects particularly on young climbers due to the observation of short stature with low body weight and body fat in sports climbers. The aim of this study was to investigate anthropometric and hormonal data for climbers of the German Junior national team. 16 climbers were compared with 14-age matched nonclimbers with respect to several anthropometric variables, leptin level, and climbing characteristics. Height, weight and body mass index (BMI) standard deviation scores (SDS) for boys were not significantly different from the controls, whereas girls had significantly lower SDS-values for weight and BMI. In comparison with the control group boys and girls had a lower skinfold thickness. The leptin values were lower than the calculated leptin levels but only reached significance for the girls. The young athletes of the GJNT were neither of short stature nor thin when compared with a physically active control group. The low body fat in boys and girls was within expected limits. The lower leptin levels might be attributed to a decrease in total body fat.     

The relationship between leptin, metabolic hormones, exercise and body composition in adolescents

During adolescence, little is known about the relationship between leptin and metabolic hormones and how these are modified by body composition and exercise. This study determined: 1) the relationships between leptin, triiodothyronine, cortisol, and insulin, and 2) whether these relationships were modified by body composition and exercise. Fasting hormonal concentrations were assessed from 80 girls and 80 boys, aged 11-18 yr. In a multiple regression model, including the hormones and gender, only gender and insulin were significant predictors of leptin (R2 = 0.394; p <0.001). In a second model, including body fat and exercise, the levels of body fat, gender, free triidothyronine and cortisol explained 59.6% of the variance in leptin (p <0.05). The results suggest that in adolescents, the relationship between leptin and insulin is mediated by body fat. Leptin is negatively associated with cortisol in boys and with thyroid hormones in girls; these hormones possibly interact to sustain normal growth and maturation.     

Changes in leptin, insulin and body composition in obese children during a weight reduction program

BACKGROUND: Girls have higher leptin concentrations than boys at all stages of biological development and this is also seen in the state of obesity. Little is known about whether gender and biological development of obese children influence changes in leptin associated with a short-term weight reduction program. OBJECTIVE: To study whether leptin concentration, body composition and insulin levels in obese children were influenced by a 3-week intervention program including diet and sports. STUDY DESIGN: Sixty-two obese children (32 boys and 30 girls) were examined before and after the intervention program. Body composition was measured by bioelectrical impedance and BMI-SDS was calculated. Serum leptin and serum insulin were determined by RIA. RESULTS: Girls had higher leptin levels than boys, before and after the weight reduction program. Body mass, fat mass (FM), leptin and insulin were decreased after the intervention in both sexes. We found a greater change in serum leptin in girls but the change in FM was of greater magnitude in boys. However, percentage changes in leptin were not significantly different between the sexes. Before the intervention, leptin concentrations were correlated with %FM, FM and moderately with BMI-SDS in all children. Only in pubertal boys did correlation of leptin with %FM increase after the intervention (from r=0.57 to r=0.75, p<0.01). Changes in leptin were found to be associated with initial leptin values in boys (r=0.95, p<0.01) and in girls (r=0.93, p<0.01), independent of Tanner stages. CONCLUSION: Serum leptin levels were positively correlated with adiposity in obese children and a diet and sports intervention program decreased serum leptin, insulin and body fat in all children. Changes in leptin were best described by the initial leptin concentration. The increase in correlation of leptin with %FM in obese pubertal boys after the intervention could have its underlying mechanism in an increased sensitivity to leptin and anabolic hormones.     

0～14岁儿童血肥胖抑素含量及其意义

目的了解0～14岁儿童血肥胖抑素(Leptin) 水平.方法对154名(男 78名,女 76名)0～14岁健康非肥胖儿童(38例)和超重/肥胖儿童(39例)的Leptin分布、性别/年龄变化趋势、与人体测量学参数(腰围、腰臀比、瘦体重、全身体脂含量、体脂百分数、BMI/Kaup指数)和血胰岛素水平的相互关系进行了研究.结果 (1)健康非肥胖儿童Leptin值为1.01～29.92 (ng/ml),均值为2.99±2.13 (ng/ml).90%可信限范围,男童为1.36～14.21 (ng/ml),女童为1.74～21.17 (ng/ml).血浆与血清Leptin值差异无显著意义;(2)超重/肥胖儿童血Leptin值明显高于非肥胖儿童(P＜0.001).(3)Leptin性别差异有显著意义(P=0.023),在非肥胖儿童中更明显(P=0.004).多元回归分析表明,加入体脂因素后性别因素不再与Leptin 水平相关(P=0.138,0.241,0.990),而BMI、体脂含量和体脂百分数的影响差异有显著意义(P＜0.001);(4)Leptin值与年龄存在相关关系(P=0.005),超重/肥胖组更著,女性随年龄增长而升高的趋势更明显(P=0.001).青春期前期Leptin值开始上升,女性明显高于男性(P=0.045).不同年龄组其Leptin值明显不同(P＜0.001).(5)Leptin值与BMI、体脂含量和体脂百分数显著正相关、与瘦体重相关关系弱,男童与腰臀比不相关,女童存在相关关系.曲线回归方程(Quadatic)比直线相关方程更好的指示上述相关.(6)0～7岁儿童Leptin值与出生体重明显相关(P=0.001),自学龄期后无相关关系(P=0.456).(7)Leptin值与空腹胰岛素水平呈正相关(P＜0.001).结论儿童血Leptin值的发育与脂肪发育及重聚规律一致.     

Change in leptin, body composition and other hormones around menarche--a visual representation

Abstract Aim: To present a visual representation of changes in body composition, leptin, insulin, estradiol and follicular stimulating hormone (FSH) levels in relation to menarche in girls. Methods: Participants were a subset of healthy girls (n = 108) enrolled in a longitudinal study of growth and development conducted at the General Clinical Research Center at the Massachusetts Institute of Technology (MIT). Participants were seen annually from before menarche until 4 years postmenarche for measures of body composition and serum levels of leptin, insulin, estradiol and FSH. Body composition was determined by bioelectrical impedance. Standardized body composition and hormone levels were smoothed and plotted relative to menarche to visualize patterns of change. Results: At menarche, the mean percentage body fat (%BF) of girls was 24.6% (SD = 4.1%) after menarche %BF was approximately 27%. Leptin levels averaged 8.4 ng/mL (SD = 4.6) at menarche and were approximately 12 ng/mL after menarche. Changes in leptin levels closely paralleled changes in %BF. Insulin, estradiol and FSH levels followed expected patterns relative to menarche. Leptin began rising closer to menarche than did insulin or the other sex hormones. Conclusion: We provide a visual presentation of hormonal and body composition changes occurring throughout the pubertal period in girls which may be useful in generating new hypotheses related to the timing of menarche.     

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.     

The relationship between different subcutaneous adipose tissue layers, fat mass and leptin in obese children and adolescents

We studied the relationships of subcutaneous adipose tissue layers (SAT-layers), body fat mass (FM) and waist-to-hip ratio (WHR) with leptin in obese children and adolescents. Twenty-nine obese children and adolescents (12 boys: age: 11.3 +/- 3.7 yr; body mass index [BMI]: 28.5 +/- 4) and 17 girls (age: 12.2 +/- 2.2 yr; BMI: 29.8 +/- 4.7) (mean +/- SD) were studied. FM was estimated by bioelectrical impedance. SAT-layers were determined at 15 different body sites from 1-neck to 15-calf by the Lipometer optical device. Leptin and insulin were determined by RIA. Maturity was associated with a greater thickness of certain SAT-layers from the upper body and with a lower thickness of SAT-layers from the abdominal region and lower extremities. Significant correlations were found for all estimates of adiposity and leptin (all p<0.001). Waist and hip circumferences were not correlated to leptin after adjustment for FM. SAT-layers from the upper body were significantly and positively correlated to leptin. Multiple regression analysis revealed FM as a main contributor to the variation in leptin (R2=0.53, p<0.0001). FM together with SAT-layers 5-front chest and 13-rear thigh explained 72% of the variation in leptin (p<0.0001). In a body fat distribution model, hip circumference together with SAT-layers 4-upper back and 2-triceps explained 75% of the variation in leptin (p< 0.0001). The results suggest that SAT-layers and their topography are main determinants for leptin in obese children and adolescents. Maturity in obese children is associated with higher values of upper body SAT-layers and lower values of abdominal and lower extremities SAT-layers. Whether leptin is under the control of certain subcutaneous adipose tissue depots from the upper body remains to be elucidated by longitudinal studies.     

Inappropriate leptin secretion in thalassemia: a potential cofactor of pubertal timing derangement

The objective of the present study was to gain a better understanding of the role played by scarce leptin production in the deranged sexual development observed in patients with thalassemia. We studied 101 patients at different stages of puberty. Patients of both sexes were divided into three groups according to Tanner stages: T1-2 (20 males and 12 females), T3-4 (9 males and 4 females) and T5 (48 males and 8 females). Serum levels of leptin, ferritin, testosterone and estradiol were assessed. Leptin levels were adjusted for body mass index (BMI) using reference ranges stratified on the basis of gender and pubertal development. Deviations from the mean reference values were evaluated by calculating the standard deviation scores. Mean leptin standard deviation scores were significantly lower than expected in pubertal stage T1-2 and T3-4 in males and T3-4 and T5 in females. The peak leptin level was delayed in boys (13 years). In girls, parallelism between leptin and BMI was present until age 7-10 years; thereafter, although BMI constantly increased, leptin levels fell dramatically. Mean ferritin levels were significantly higher in pubertal stage T1-2 among males and in T5 among females. These findings show that in thalassemia adipose tissue is unable to assure adequate leptin production just when the highest leptin secretion is required and suggest that this inappropriate leptin secretion may be a cofactor of the derangement in pubertal timing observed in patients with thalassemia.