Complex HTR2C linkage disequilibrium and promoter associations with body mass index and serum leptin

The occurrence of obesity, eating disorders, and related diseases has increased in many parts of the world. Given that few strong genetic factors have been found, it is clear that these are complex multi-factorial diseases. The serotonin receptor 2C, a member of the 5-HTergic system, has been implicated in the control of phagia and obesity. We report a detailed investigation of linkage disequilibrium (LD) within and between the HTR2C promoter and the flanking sequences around a commonly utilized marker in the second coding exon of HTR2C. We suggest that inconsistent associations between HTR2C and several phenotypes, including obesity, may be due to the LD pattern across the gene in which recombination and gene conversion have been influential. The nucleotide and haplotype distribution is consistent with that of the neutral mutation model. The number of haplotypes suggests demographic influences or over dominant selection that may have a function in HTR2C expression. Using the fine LD pattern, we describe a possible association with promoter haplotypes and diplotypes, including a GT microsatellite, and body mass index (BMI) 30 kgm^–2 (P<0.0001). SNP –995G>A heterozygotes, as well as promoter diplotypes, were found to marginally influence higher serum leptin corrected for percentage body fat (P=0.01), which might suggest that these subjects are leptin resistant. Our results complement previous studies of HTR2C in both mice and humans, and suggest the importance of genetic variation and elucidating the fine LD structure in uncovering the genetic factors of obesity.Electronic Supplementary Material Supplementary material is available for this article at     

长期强迫运动对布氏田鼠体重和血清瘦素浓度的影响

动物稳定体重的维持需要能量摄入和消耗之间的平衡.运动是影响动物能量平衡的重要因素之一.为了理解运动对布氏田鼠的生理学效应,我们在室内条件下,运用踏车测定了强迫运动训练6周后动物的体重、体脂含量、摄食量和瘦素浓度的变化.摄食量采用代谢笼法测定,体脂含量采用索氏提取法,血清瘦素含量采用放免试剂盒测定.结果发现强迫运动训练6周对布氏田鼠的体重和摄食量都无显著影响,与非运动训练组田鼠相比,运动训练组田鼠的身体脂肪重量降低了3.5 g,运动组田鼠的血清瘦素水平比对照组下降了30%.对照组田鼠的血清瘦素与体脂含量具有明显的相关性,但运动组则不具有相关性.这些结果表明在强迫运动训练期间布氏田鼠不是通过增加食物摄入,而可能是通过动员贮存的脂肪和减少非活动性能量消耗等方式来维持自身的能量平衡.瘦素在长期强迫运动训练过程中对身体脂肪含量的变化具有调节作用.     

Growth hormone treatment downregulates serum leptin levels in children independent of changes in body mass index

The changes in serum leptin levels during growth hormone (GH) treatment were studied in 27 children, 17 with GH deficiency (GHD), 10 with idiopathic short stature (ISS), and 9 with Prader-Willi syndrome (PWS). Within 1 month of GH treatment, serum leptin levels decreased by 40% in the GHD children (p < 0.01). There was no significant change in serum leptin level in the children with ISS. In children with PWS, the mean serum leptin level decreased by almost 60% after 3 months of treatment (p < 0.001). Thereafter, no further decline was observed in any of the 3 groups. Changes in body composition became evident first after the 3 months of treatment. In the GHD children, the BMI was unchanged while the mean body fat percentage was 2.7% lower after 1 year of GH treatment (p < 0.05). In the ISS children, neither BMI nor body fat percentage were significantly changed during treatment. The PWS children exhibited a significant decrease in BMI after 6 months of GH treatment without any further change during the remaining period of treatment. In this group, the mean body fat percentage decreased from 42 +/- 2.4 to 28 +/- 2.2% after treatment (p < 0.001). The finding that the fall in leptin occurs before changes in body composition become detectable suggests a direct effect of GH on leptin production, metabolism, or clearance.     

禁食和重喂食对大绒鼠体重、产热和血清瘦素的影响

动物行为和生理活动的适应性调节是应对食物资源变化的主要策略。为探讨禁食和重喂食对大绒鼠体重、产热和血清瘦素的影响,测定了禁食和重喂食条件下大绒鼠的体重、体脂重量、静止代谢率、身体组成、血清瘦素含量以及禁食后重喂食期间的摄食量。结果显示:禁食导致大绒鼠体重、体脂重量和静止代谢率显著下降,重喂食后体重和静止代谢率能够恢复到对照组水平,而体脂重量却不能恢复。禁食12 h 后血清瘦素含量快速下降,重喂食后未能恢复到对照水平。此外,大绒鼠在禁食后重喂食期间摄食量没有补偿性增加,血清瘦素含量与体脂重量呈正相关关系。这些结果很可能反映出大绒鼠能调节自身生理状况以适应短期的能量缺乏,主要通过降低体重、血清瘦素含量和代谢活性器官重量以减少能量消耗。禁食后重喂食时大绒鼠没有摄食过量。血清瘦素的下降早于体重和体脂的下降。     

The relationship between body mass index, semen and sex hormones in adult male

This study was aimed at evaluating the relationship between body mass index, sex hormones and semen characteristics in male adults. 120 male adults aged 20 to 50 years who consented to participate in the study were used. Serum samples collected from each subject were analyzed for Luteinizing hormone (LH), Follicle stimulating hormone (FSH), Prolactin (PRL), Progesterone, Estradiol and testosterone by classical ELISA method. Semen samples obtained by masturbation after 72 hours of abstinence were analyzed for sperm count and motility. The results showed statistically significant correlations at 99% confidence level between body mass index and serum concentrations of progesterone and oestradiol and sperm count. No significant correlations were observed between body mass index and sperm motility, serum concentrations of prolactin, testosterone and luteinizing hormone. In conclusion, this study has shown that statistically significant correlations exist between body mass index, semen characteristics and male sex hormones and may broaden our understanding of the physiology of male fertility/infertility. Keywords: Body mass index, Semen quality, Male sex hormones, Fertility/infertility.     

Age and body mass index associations with body segment parameters

Body segment parameters (BSPs) such as segment mass, center of mass, and radius of gyration are required in many ergonomic tools and biomechanical models to estimate injury risk, and quantify muscle and joint contact forces. Currently, the full effects of age and obesity have not been taken into account when predicting BSPs. The goal of this study is to quantify the impact of body mass index (BMI) and age on BSPs, in order to provide more representative measures necessary for modeling inputs. A whole body dual energy X-ray absorptiometry (DXA) scan was collected for 280 working men and women with a wide range of BMI and aged 21 to 70 years. Established DXA processing methods were used to determine in-vivo estimates of the mass, center of mass, and radius of gyration for the upper arm, forearm, torso, thigh, and shank for males and females. Regression models were used to determine if age and BMI terms, as well as their interactions, were associated with these BSPs. The variability in BSPs explained by BMI alone ranged from 4 to 51%, and age explained an additional 3–19%. Thus, BMI and age are significant correlates of BSPs, and need to be taken into account when predicting certain BSPs in order to obtain accurate and representative results in biomechanical models.     

Measuring adiposity in patients: the utility of body mass index (BMI), percent body fat, and leptin

Background

Obesity is a serious disease that is associated with an increased risk of diabetes, hypertension, heart disease, stroke, and cancer, among other diseases. The United States Centers for Disease Control and Prevention (CDC) estimates a 20% obesity rate in the 50 states, with 12 states having rates of over 30%. Currently, the body mass index (BMI) is most commonly used to determine adiposity. However, BMI presents as an inaccurate obesity classification method that underestimates the epidemic and contributes to failed treatment. In this study, we examine the effectiveness of precise biomarkers and duel-energy x-ray absorptiometry (DXA) to help diagnose and treat obesity.

Methodology/Principal Findings

A cross-sectional study of adults with BMI, DXA, fasting leptin and insulin results were measured from 1998–2009. Of the participants, 63% were females, 37% were males, 75% white, with a mean age = 51.4 (SD = 14.2). Mean BMI was 27.3 (SD = 5.9) and mean percent body fat was 31.3% (SD = 9.3). BMI characterized 26% of the subjects as obese, while DXA indicated that 64% of them were obese. 39% of the subjects were classified as non-obese by BMI, but were found to be obese by DXA. BMI misclassified 25% men and 48% women. Meanwhile, a strong relationship was demonstrated between increased leptin and increased body fat.

Conclusions/Significance

Our results demonstrate the prevalence of false-negative BMIs, increased misclassifications in women of advancing age, and the reliability of gender-specific revised BMI cutoffs. BMI underestimates obesity prevalence, especially in women with high leptin levels (>30 ng/mL). Clinicians can use leptin-revised levels to enhance the accuracy of BMI estimates of percentage body fat when DXA is unavailable.     

Body mass index modulates the relationship of sugar-sweetened beverage intake with serum urate concentrations and gout

IntroductionBoth sugar-sweetened beverage (SSB) intake and body mass index (BMI) are associated with elevated serum urate concentrations and gout risk. The aim of this study was to determine whether the associations of SSB intake with serum urate and gout are moderated by BMI.MethodThe effects of chronic SSB intake on serum urate and gout status were analysed in a large cross-sectional population study. The effects of an acute fructose load on serum urate and fractional excretion of uric acid (FEUA) were examined over 180 minutes in a short-term intervention study. In all analyses, the responses were compared in those with BMI <25 mg/kg² (low BMI) and ≥25 mg/kg² (high BMI).ResultsIn the serum urate analysis (n = 12,870), chronic SSB intake was associated with increased serum urate in the high BMI group, but not in the low BMI group (P_difference = 3.6 × 10⁻³). In the gout analysis (n = 2578), chronic high SSB intake was associated with gout in the high BMI group, but not in the low BMI group (P_difference = 0.012). In the acute fructose loading study (n = 76), serum urate was increased in the high BMI group at baseline and throughout the observation period (P_{BMI group} <0.0001), but there were similar acute serum urate increases in both BMI groups in response to the fructose load (P_interaction = 0.99). The baseline FEUA was similar between the two BMI groups. However, following the fructose load, FEUA responses in the BMI groups differed (P_interaction <0.0001), with increased FEUA at 120 minutes and 180 minutes in the low BMI group and reduced FEUA at 60 minutes in the high BMI group.ConclusionsThese data suggest that BMI influences serum urate and gout risk in response to chronic SSB intake, and renal tubular uric acid handling in response to an acute fructose load. In addition to many other health benefits, avoidance of SSBs may be particularly important in those with overweight/obesity to prevent hyperuricaemia and reduce gout risk.

Trials registration

Australian Clinical Trials Registry ACTRN12610001036000. Registered 24 November 2010.     

Measurement of steroid sex hormones in serum: a comparison of radioimmunoassay and mass spectrometry

Concern has been raised about the adequacy of radioimmunoassays to measure steroid sex hormones in population studies. We compared steroid sex hormone measurements in serum by radioimmunoassay with mass spectrometry. Four male and four female serum pools with known relative concentrations of steroid sex hormones were measured multiple times by both methods. Because measurements are expected to increase linearly with concentration for each sex, we examined whether the linear regressions of hormone measurements on concentration were the same for radioimmunoassay and mass spectrometry. Estradiol, estrone, androstenedione, testosterone, and dehydroepiandrosterone sulfate were measured in female pools; testosterone, dihydrotestosterone, androstenedione, and dehydroepiandrosterone sulfate were measured in male pools. Regression slopes for radioimmunoassay and mass spectrometry measurements were comparable for all hormones except androstenedione, which had a steeper slope when measured by mass spectrometry (P < or = 0.02). Intercepts for radioimmunoassay and mass spectrometry were similar and close to zero for estradiol, androstenedione, dehydroepiandrosterone sulfate, and in male samples, testosterone. For testosterone in female samples, estrone, and dihydrotestosterone, radioimmunoassay and mass spectrometry intercepts differed significantly. Standard deviations of individual measurements by radioimmunoassay and mass spectrometry differed by hormone and serum concentration; neither method consistently measured hormone concentrations with less variability. Our findings suggest that although absolute concentrations may differ for some hormones, radioimmunoassay and mass spectrometry can yield similar estimates of between subject differences in serum concentrations of most steroid sex hormones commonly measured in population studies. Relative power of studies using radioimmunoassay and mass spectrometry will depend on the hormones measured and their serum concentrations.     

Overweight in urban schoolchildren assessed by body mass index and body fat mass in Dalian, China

In order to assess overweight in urban schoolchildren (298 boys and 298 girls) aged 9-16 years in Dalian, China, their body height, weight, skinfolds at triceps, biceps, subscapular and suprailiac, and body circumferences of mid-upper arm, waist and hip were measured. The results showed that the prevalence of overweight, based on the United States Centers for Disease Control 2000 reference values using body mass index (BMI), was 22.9% in boys and 10.4% in girls, which was higher than that of indicated in Chinese national surveys of recent decades. More boys were overweight than girls due to excessive increase in body fat, although the prevalence of overweight in girls prevalence increased from 13 years. Discussion here focuses on the effects of behavioral patterns on overweight in Dalian schoolchildren, paying attention to gender difference.     

Reproduction in high body condition mares with high versus low leptin concentrations

Previous results from our laboratory indicated that a majority of mares with high body condition scores (BCS) displayed estrous cycles or had considerable follicular activity during the winter. Among these high BCS mares, about 35% of them exhibited a persistent hyperleptinemia and hyperinsulinemia. The current experiment was designed to compare the reproductive characteristics of high BCS mares with hyperleptinemia to those with normal (low) plasma concentrations of leptin during the winter and the first estrous cycle (or the first full cycle encountered for those already cycling). Light horse mares with high BCS (6-8.5) were assigned to groups based on leptin concentrations (8/group): low (<5 ng/mL) and high (>10 ng/mL). Beginning 7 January, mares were assessed every 3d for follicular activity and then daily once a follicle >25 mm was detected. Mares were subsequently monitored through their first and second ovulations. Leptin concentrations remained higher (P<0.001) in mares in the high leptin group over the duration of the experiment. Also, high leptin mares had greater (P<0.0001) insulin response to glucose infusion and a faster (P<0.05) rate of glucose clearance. One mare with high leptin and three mares with low leptin had progesterone concentrations indicative of the presence of a corpus luteum at the onset of the experiment. Plasma concentrations of LH, FSH, and progesterone did not differ between groups (P>0.1) during the first estrous cycle occurring after 7 January. Date of first ovulation after 7 January and interovulatory interval were similar (P>0.1) for the two groups, as were estimates of follicular numbers on the ovaries (small, medium, and large; P>0.1). It is concluded that the perturbations in leptin and insulin secretion observed in some high BCS mares are not associated with alterations in ovarian activity or the estrous cycle during winter and into the period of vernal transition.     

Income and body mass index in Europe

The problem of obesity is alarming public health authorities around the world. Therefore, it is important to study its determinants. In this paper, we explore the empirical relationship between household income and body mass index (BMI) in nine European Union countries. Our findings suggest that, in general, the association is negative for women and nonexistent for men. Moreover, once we decompose household income into “own labor earnings” and “other household income”, we find that the different relationship for men and women appears to be driven by the negative relationship between BMI and “own labor earnings” for women.     

Perceived psychological stress and serum leptin concentrations in Japanese men

Objective: To examine epidemiologically whether subjects with higher stress perception levels have higher leptin concentrations. Research Methods and Procedures: In this cross‐sectional study, the study population comprised 1062 male workers at local government offices in central Japan. Self‐administered questionnaires were distributed in 1997. Awareness of stress was assessed by the question: “Do you have much stress in your life?” and participants were asked to select from four possible responses: “very much,” “much,” “ordinary,” or “little.” Blood samples were also collected after fasting 12 hours overnight to determine serum leptin concentrations. Results: The mean (standard deviation) age and BMI were 50.2 (6.4) years and 23.3 (2.6) kg/m², respectively. Crude leptin concentrations according to stress categories were 2.86, 3.26, 3.32, and 3.54 ng/mL, respectively, and leptin concentrations adjusted for age, BMI, physical activity, drinking and smoking habits, overtime work, shift work, sleep duration, and availability of confidants were 2.96, 3.24, 3.34, and 3.43 ng/mL for “little,” “ordinary,” “much,” and “very much,” respectively (p = 0.03 by one‐way analysis of covariance; p < 0.01 by test of linear trend). Significant associations were also observed among the level of perceived psychological stress and work‐related stressors, variables related to sleep, and other psychological variables. Discussion: This study showed that subjects who perceived psychological stress had high leptin levels, which provides epidemiological evidence that psychological stress may have the potential effect of increasing blood levels of the pleiotropic peptide, leptin.     

Development and validation of competitive ELISA to determine follicular fluid progesterone concentrations

A simple, direct and reliable heterologous ELISA was developed and validated to determine follicular fluid progesterone concentrations in 10- to 20-mm antral follicles in heifers. A competitive ELISA was developed, using a policlonal antisera raised in New Zealand white rabbits and horseradish peroxidase as label. Standard curve covered a range between 0 and 1 ng per well. The intra- and inter-assay coefficients of variation (CV) were 6.54 and 8.27%, respectively (n = 10). The low detection limit was 1 pg per well with a sensitivity of 50% binding 83.17 pg per well. Comparison of ELISA with RIA showed a correlation coefficient of 0.98. A total of 34 follicles obtained from heifers in the follicular phase of the estrous cycle were tested, and the mean progesterone concentration was 86.72 +/- 20.39 ng/ml. These results were similar to those previously reported for the same species, age, follicular size and stage of cycle.