瘦素、肥胖与青春期发育

瘦素是由肥胖基因编码的一种分泌型的蛋白质，其作用主要在于调节体重、脂肪和能量代谢。青春期的发动需要一定量的体重或是体脂的贮存，瘦素可能是脂肪组织发出的给生殖系统一种特殊的代谢信号。现就瘦素与肥胖及青春期发育关系的研究进展作以综述。     

瘦素:一种生殖功能的代谢信号

瘦素是肥胖基因编码 ,脂肪组织分泌的蛋白质 ,已知其主要功能是调控进食、能量消耗及体重。近年来瘦素在生殖方面的作用备受关注 ,许多研究表明瘦素与青春期发育、育龄期妇女的月经变化、排卵功能、妊娠以及老年妇女的衰老有着重要联系 ,从而推测瘦素可能是一种生殖功能的代谢信号。本文就主要围绕着这个观点做一概述。     

瘦素：一种生殖功能的代谢信号

瘦素是肥胖基因编码，脂肪组织分泌的蛋白质，已知其主要功能是调控进食、能量消耗及体重。近年来瘦素在生殖方面的作用备受关注，许多研究表明瘦素与青春期发育、育龄期妇女的月经变化、排卵功能、妊娠以及老年妇女的衰老有着重要联系，从而推测瘦素可甬一种生殖功能的代谢信号。本文就主要围绕着这个观点做一概述。     

营养状况与瘦素水平研究进展

瘦素(leptin)是一种主要由白色脂肪细胞合成和分泌的多肽类激素,是肥胖基因(obese,ob)编码产物.其分泌具有一定的节律性,晚上高,早上低,并呈脉冲式分泌[1].瘦素主要通过肾脏排泄.机体营养状况与瘦素之间具有十分密切的联系,瘦素通过抑制食欲、减少能量摄取、抑制脂肪合成、增加能量消耗等途径调节能量代谢,具有调节体重、参与体内物质和能量代谢的生物学效应.瘦素已成为近年生命科学研究的热点之一.本文旨在对瘦素与肥胖、瘦素营养代谢不良、瘦素与胎儿期及青春期营养关系的研究进展作一综述.     

瘦素与女性生殖的关系

瘦素（leptin）作为一种调节代谢的因子，是由脂肪组织分泌的，它通过下丘脑的受体而发挥减少人体对食物的摄入、增强能量消耗使体重下降的作用。在人类，无论男女，瘦素水平均与肥胖程度成正比。另外，在女性，瘦素也可以由子宫内膜、胎盘及卵巢等外周组织合成分泌及发挥作用。瘦素在青春期开始上升，绝经后下降，提示瘦素水平的改变与生殖活动有一定关系。     

肥胖儿童血清瘦素指标检测及其与中枢性性早熟女童青春期发育关系的探讨

目的:观察肥胖儿童血清瘦素水平,探讨瘦素和体重指数(BMI)的关系,同时研究特发性中枢性性早熟(ICPP)女孩青春各期血清瘦素变化规律。方法:肥胖组为2002~2004年度在吉林省医院门诊就医的体重高于同年龄小儿标准体重20?的患儿50例,对照组为体检正常的儿童50例,年龄均为5~11岁;另外选择35例处于青春各期的特发性中枢性性早熟女孩(ICPP)为观察组,以17例正常青春前期女孩作为对照组。分别测量各组瘦素和BMI。结果:(1)肥胖儿童血清瘦素水平均高于非肥胖儿童,与BMI呈正相关;(2)ICPP女孩青春早、中、晚期血瘦素均高于对照组(P<0.05)。结论:(1)儿童瘦素水平与BMI高度相关,肥胖儿童存在瘦素抵抗现象。(2)ICPP女孩血清瘦素水平均在青春早期明显升高并与青春期发育过程平行。     

瘦素在女性青春期发育中的作用

目的 探讨瘦素在女性青春期发育中的作用及其与胰岛素、生长激素、雌二醇和睾酮的相互关系。方法 2001年9月筛选7－17岁单纯性肥胖女性150人,以相互身高相差不超过2cm,年龄相差不超过3个月进行配比,选择正常组和营养不良组各150人。结果 女性血清瘦素水平与体重指数和年龄均呈正相关。女性血清瘦素水平从B1期到B5期逐步上升。正常组B2期血清瘦素水平（7.72μg/L）和营养不良组B2期（7.36μg/L)相近,但显著低于肥胖组B2期血清瘦素水平（12.85μg/L),其他各期肥胖组、正常组和营养不良组均差异有显著性。瘦素与生长激素呈负相关,与胰岛素呈强正相关,但与雄二醇和睾酮无相关性。结论 瘦素在启动女性青春期发育中可能发挥了作用。B2期瘦素水平可能是瘦素启动女性青春期发育的阈剂量。B5期瘦素水平迅速增长具有抑制生长激素分泌的作用,起到青春期发育结束信号的作用。     

单纯性肥胖女孩3种激素水平及与BMI的关系

目的探讨不同年龄段单纯性肥胖女孩的血清瘦素(Leptin)、雌二醇(E2)、胰岛素(Ins)3种激素水平和内分泌相互作用及与体重指数(BMI)之间的关系,以便为青春期女生生长发育的研究提供依据.方法对荥阳市6所中小学女生2 000名测量体重后,从筛查出的单纯性肥胖儿童中随机抽取60名,同时从正常体重女生中抽取60名为对照.按年龄分组,分别用放射免疫方法(RIA)测定其血清3种激素的含量.结果各年龄组对照组和肥胖组女孩的Leptin和Ins水平差异有显著性(P＜0.05),各年龄组Leptin和Ins水平与BMI有明显的相关性(P＜0.05).结论 3种激素水平均随年龄、体重和BMI的升高而升高.肥胖女孩的Leptin和Ins分泌紊乱.瘦素水平能从一定程度上反应肥胖的程度,结合内分泌水平可对肥胖程度以准确评价.     

瘦素与女性不孕

瘦素(leptin)最初是作为“能量代谢信号”呈现于人们面前,而随着对其研究的深入,人们发现瘦素对生殖功能也有重要的调节作用。研究发现,在女性的各类不孕状态中,如肥胖、极瘦(厌食症)、运动员、青春期前、绝经后、多囊卵巢综合症,均伴有瘦素水平的异常变化,说明瘦素与女性不孕密切相关。瘦素可以通过调节体重而调节生殖功能。在下丘脑,瘦素作为一种代谢信号可以调节下丘脑-垂体-性腺轴。在卵巢组织中,瘦素与其受体结合可以直接调节卵巢功能。此外,瘦素亦可影响着床。体内一定水平的瘦素是生殖功能正常的前提,过高或过低破坏这种平衡,部可能破坏生殖功能。     

血清瘦素与青春期肥胖儿童高血压的相关性研究

【目的】探讨血清瘦素浓度与青春期肥胖儿童高血压的关系。【方法】测定32例肥胖高血压患儿、31例单纯性肥胖患儿和34例健康自愿者的空腹血清瘦素浓度、收缩压(SBP)、舒张压(DBP)、腰围,计算体质指数(bodymass index,BMI)和平均动脉压(MAP),采用酶联免疫分析法(ELISA法)测定血清瘦素相对浓度,分析瘦素与上述各项参数的相关性。【结果】①肥胖高血压组和单纯性肥胖组血清瘦素浓度显著高于正常组(P<0.05),肥胖高血压组血清瘦素浓度高于单纯性肥胖组(P<0.05);②正常组、单纯性肥胖组和肥胖高血压组女童的血清瘦素浓度均分别显著高于同组男童(P<0.05);③瘦素与BMI、SBP、DBP和腰围呈正相关性。【结论】肥胖儿童血清瘦素水平升高,且血清瘦素水平与血压之间有相关关系,推测血清瘦素可能参与了青春期肥胖儿童高血压的发生发展过程。     

Leptin: Defining Its Role in Humans by the Clinical Study of Genetic Disorders

Extremely unusual genetic conditions can reveal normal processes governing physiologic regulation and metabolism. Children with rare homozygous mutations in the leptin gene and complete leptin deficiency develop extreme hyperphagia and obesity soon after birth but respond with normal eating and a selective loss of excess body fat upon being given small amounts of leptin. Heterozygote relatives have 30% more fat than predicted and relatively low leptin levels. This demonstrates leptin's fundamental involvement in maintaining energy balance. Leptin also seems to act as a metabolic gate allowing children to enter puberty.     

Relation between hormones and body composition, including bone, in prepubertal children

BACKGROUND: Sex differences in body composition exist before puberty, but the reason for this phenomenon is unknown. The physical changes that occur during puberty are mediated, in part, through sex steroids, insulin-like growth factor I (IGF-I), and leptin. However, data are lacking that address the extent to which concentrations of these hormones influence body composition, bone mass, and density in prepubertal children. OBJECTIVE: We investigated the effects of IGF-I, dehydroepiandrosterone sulfate, and sex steroids on body composition and fat distribution and the effects of these hormones and leptin on total body bone mineral content (TBMC) and volumetric bone mineral density (vBMD) at the femoral neck and lumbar spine (LS) in 255 healthy children (137 girls), aged 7-8 y. DESIGN: Body composition, fat distribution, TBMC, and vBMD were derived by using dual-energy X-ray absorptiometry. Association between variables was examined by using regression analysis. RESULTS: No sex differences were found in age, height, or weight. However, girls had significantly more total body fat, trunk fat, and higher LS vBMD but significantly less fat-free soft tissue, TBMC, and femoral neck vBMD than did boys. Girls also had significantly (P < 0.001) higher IGF-I, estradiol, testosterone, and leptin concentrations than did boys. Estradiol concentrations predicted percentage body fat, which supported an effect of estrogen on fat storage. Leptin had an independent effect on LS vBMD, which suggests a positive effect for leptin on trabecular bone. CONCLUSIONS: The hormones examined explained 3-17% of the variations in body-composition measures, fat distribution, and bone density, which suggests that other factors are important predictors of prepubertal sexual dimorphism.     

青春期女性血清瘦素及可溶性瘦素受体的双生子研究

目的探讨青春期女性血清瘦素及可溶性瘦素受体的变化趋势,估计遗传与环境因素的相对效应。方法以学校登记为基础募集6～18岁女性双生子180对,其中同卵双生子132对、异卵双生子48对,按Tanner标准进行青春发育分期,测定空腹血清瘦素和可溶性瘦素受体浓度。结果青春期女性血清瘦素浓度随青春期进展而显著增高,可溶性瘦素受体则呈显著下降趋势。二者的综合作用使得游离瘦素指数随青春期进展持续增高,7～9岁和12—14岁增高尤为显著,分别为10．1～32．3和41．8～82．1;瘦素和游离瘦素指数与各体格指标呈显著正相关(r值为0．54～0．76),而可溶性瘦素受体则与各指标呈显著负相关(r值为-0．23～-0.42);各指标组内相关系数均为同卵双生子大于异卵双生子,而偶内差和相似度系数则异卵双生子大于同卵双生子,瘦素、可溶性瘦素受体和游离瘦素指数的遗传度分别为0．37、0.84和0.46。结论7～9岁女孩游离瘦素指数的快速增长可能对青春期的启动起促进作用,而12—14岁的突增可能对即将到来的月经初潮起预示作用。青春期女孩血清游离瘦素指数同时受遗传与环境因素的影响,瘦素受环境因素的影响较大,可溶性瘦素受体则受遗传因素的影响较强。     

Serum leptin concentrations during the menstrual cycle in Iranian healthy women

Leptin, a circulating 16-kd polypeptide consisting of 167 amino acids, appears to be involved in the body weight homeostasis. Moreover leptin plays an important role for the reproductive system, early embryogenesis, and fat metabolism during pregnancy and puberty. Significant correlations have been found between leptin and sexual hormones, which is a cytokine and has hormonal properties. The aim of this study was to determine serum leptin levels during the menstrual cycle, and the association between serum leptin and reproductive hormones in young, healthy Iranian women. 42 healthy women volunteered for the study. They all had regular menstrual cycles, with cycle length varying between 26 and 32 days. None of them used oral contraceptives. All were of normal weight, with body mass index ( BMI) < 25 Kg/m2. Fasting blood samples were collected during the follicular phase, mid cycle and luteal phase of the menstrual cycle. FSH and LH were measured with coated tube immunoradiometric assay. Estrogen and progesterone were measured using antibody -coated tubes. Serum Leptin concentration were measured by Leptin (sandwich) ELISA. In menstruating women, serum leptin increased from 13.15+/-1.60 ng/ml in the early follicular phase to 16.57+/-1.68 ng/ml (P<0.01) at the luteal phase. Serum leptin concentration negatively correlated with LH and progesterone (P<0.05). Mean serum leptin levels correlated with body mass index (BMI) (r =0.78, P<0.001).     

Relation of leptin to insulin resistance syndrome in children

OBJECTIVES: To examine the relation of leptin to insulin resistance, as measured by euglycemic insulin clamp, and insulin resistance syndrome factors in thin and heavy children. RESEARCH METHODS AND PROCEDURES: Anthropometrics, insulin, blood pressure, and leptin were measured in 342 11- to 14-year-old children (189 boys, 153 girls, 272 white, 70 black). Insulin sensitivity (M) was determined by milligrams glucose uptake per kilogram per minute and expressed as M/lean body mass (Mlbm). Children were divided by median BMI (boys = 20.5 kg/m(2); girls = 21.4 kg/m(2)) into below-median (thin) and above-median (heavy) groups. Correlation coefficients between log-leptin and components of insulin resistance syndrome were adjusted for Tanner stage, gender, and race. RESULTS: BMI was related to leptin in boys (r = 0.70, p < 0.001) and girls (r = 0.75, p < 0.001). Leptin was higher in girls than boys (32.6 vs. 12.3 ng/mL, p = 0.0001). Leptin levels increased in girls and decreased in boys during puberty, paralleling the changes in body fat. Leptin was significantly correlated with insulin, Mlbm, triglycerides, and blood pressure in heavy children and only with insulin in thin children. After adjustment for body fat, the correlations remained significant for insulin and Mlbm in heavy children and with insulin in thin children. DISCUSSION: Significant associations were found between leptin and insulin resistance in children, and these associations were attenuated by adjustment for adiposity. These findings at age 13 likely have long-term consequences in the development of the obesity-insulin resistance-related cardiovascular risk profile.     

Serum leptin in elderly people: associations with sex hormones, insulin, and adipose tissue volumes

OBJECTIVE: There are few data for associations of serum leptin with body fat, fat distribution, sex hormones, or fasting insulin in elderly adults. We hypothesized that the sex difference in serum leptin concentrations would disappear after adjustment for subcutaneous, but not visceral body fat. Serum leptin would not be associated with sex hormone concentrations or serum fasting insulin after adjusting for body fat and fat distribution. RESEARCH METHODS AND PROCEDURES: Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes were measured using magnetic resonance imaging in a cross-sectional sample of 56 nondiabetic, elderly men and women aged 64 years to 94 years. Serum leptin, sex hormones (testosterone and estrone), sex hormone-binding globulin, and fasting insulin were also measured. Nine women were taking hormone replacement, and five men were clinically hypogonadal. RESULTS: Leptin was significantly associated with both SAT and VAT in each sex. Adjustment for SAT reduced the sex difference in leptin by 56%, but adjustment for VAT increased the difference by 25%. Leptin was not associated with serum estrone or hormone replacement therapy in the women, but had a significant, negative association with testosterone in the men that was independent of SAT, but not VAT. Leptin was significantly associated with fasting insulin in both sexes independent of age, sex hormones, sex hormone-binding globulin, VAT and SAT. DISCUSSION: Sex difference in serum leptin is partly explained by different amounts of SAT. Studies including both men and women should adjust for SAT rather than total body fat that includes VAT. The sex difference in serum leptin is not due to estrogen, but may be partly explained by testosterone. Testosterone is negatively associated with leptin in men, but the association is confounded with VAT. Leptin is associated with fasting insulin in nondiabetic elderly men and women independent of body fat, fat distribution, or sex hormones.     

Leptin, nutrition and reproduction: new insights

Recent data suggest that in addition to leptin's role in conveying signals of the amount of energy stores to the central nervous system, this adipocyte secreted hormone interacts with the endocrine system to provide critical information about the size of fat stores, acting as a permissive factor that allows the triggering of energy demanding situations as the onset of puberty and reproduction. Animal and human data are concordant with the concept that leptin plays an important permissive role in the initiation of puberty and in maintenance of reproductive function thereafter. Leptin regulates the gonadotropin-gonadal axis at a central level. The hypothalamus is an important site of leptin's action where a complex network of neuropeptides is involved in leptin's effect on GnRH. In addition, leptin plays a role during pregnancy and lactation as it is produced by the placenta and is present in milk. Plasma leptin levels are elevated during pregnancy and this hyperleptinemia is not accompanied by a reduction in food intake, suggesting a state of leptin resistance. Leptin is also detected in the amniotic fluid and its levels are high in venous cord blood at delivery correlating positively with weight at birth which suggests a potential role in intrauterine growth. The fact that in females leptin levels are higher than in males, even when corrected for body fat, suggests that the reproductive system is modulated by leptin in a different way in males and females estrogens. In hypoleptinemia resulting from specific genetic causes, leptin levels may still be adequate for the function of the reproductive system in humans, a phenomenon which differs from the findings in leptin-deficient animals which are infertile. Due to species differences in the role of leptin, it is difficult to extrapolate data from rodents to human physiology. However hypoleptinemia due to non-genetic causes such as anorexia nervosa and exercise leads to loss of reproductive function. Genetic/developmental factors influence the threshold required to turn off the behavioral, metabolic and endocrine responses to perceived caloric deprivation.     

Serum leptin concentrations in patients with short-bowel syndrome

BACKGROUND: Short-bowel syndrome is a state of severe malabsorption resulting from absence or removal of the small bowel for several causes. A number of short-bowel patients develop hyperphagia. Leptin, a protein secreted from adipose tissue, signals the amount of energy stores to the brain. OBJECTIVE: To study body composition and leptin regulation in short-bowel patients and to determine whether or not leptin concentrations are linked with hyperphagia. DESIGN: We studied 25 short-bowel patients (remnant bowel less than 150 cm) and 31 controls and 10 oral nutrition. Fifteen patients received total parenteral nutrition and 10 oral nutrition. Anthropometric measurements, body composition (by bioelectrical impedance), and cholesterol, triacylglycerol and leptin concentrations were studied in all subjects. RESULTS: There were no differences between short-bowel patients and controls in anthropometric variables, body composition, or leptin concentrations. Leptin concentrations were higher in short-bowel women than men (9.21+/-8.54 vs. 3.22+/-1.86 ng/ml, P=0.01). Leptin concentrations correlated positively with age (r=0.4, P=0.045), body mass index (r=0.52, P=0.007), fat mass (r=0.67, P=0.001) and body fat (r=0.68, P=0.0001); there were no correlations with other body composition parameters. We found no correlations between parenteral or oral nutrition and body composition parameters, or between leptin concentrations and the presence of hyperphagia. Logistic regression analysis showed that body fat correctly identified leptin concentrations in 60% of patients. CONCLUSIONS: Body composition, leptin concentrations and leptin regulation in patients with short-bowel syndrome are similar to those of controls. Leptin concentrations do not correlate with hyperphagia in short bowel-patients.     

北京市西城区青春前期汉族女生体成分分析

目的 :　探讨北京市西城区汉族女生的体成分 ,以及与青春发育的关系。方法 :　用双能 X线吸收仪 (DEXA)测定 3 6 0名平均年龄为 1 0 .1岁的汉族女生的体成分 ,用 Tanner五分期法判定乳房和阴毛发育程度 ,询问月经初潮情况。结果 :　研究对象的全身骨矿物含量、瘦体重和体脂平均分别为 1 .3 4± 0 .2 0 kg、2 1 .2± 3 .5 kg和 1 0 .9± 4.5 kg(x± s) ,体脂百分比平均为 (3 1 .9± 8.0 ) %;随着乳房发育分期增加 ,其全身骨矿物含量、瘦体重、体脂以及体脂百分比均显著增加(P<0 .0 5 ) ,随月经初潮出现也呈类似趋势 ,但随着阴毛发育上述趋势并不显著。结论 :　青春前期女生体成分随青春发育发生显著变化。     

瘦素在人类青春期的作用

肥胖基因的蛋白产物瘦素 ,对控制摄食和能量消耗起重要作用。瘦素作为连接营养与生殖的代谢信号 ,具有启动和促进啮齿类动物性发育的作用 ,在人类青春期发育中有相似的作用。