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Relationship of serum leptin levels with body composition and sex steroid and insulin levels in men and women.

Whether the higher serum leptin levels in women are due to gender differences in fat mass or to other factors such as sex steroids remains unclear. In addition to sex steroids, serum insulin levels also appear to be related to leptin levels, although whether this effect is independent of the effects of body composition is unclear. The purpose of this study was to identify the major determinants of circulating serum leptin levels. We studied a large, population-based cohort of 345 men (23 to 90 years), 137 premenopausal women (21 to 54 years), and 212 postmenopausal women (34 to 94 years), including 47 women on hormone replacement therapy (HRT). Serum leptin levels were related to body composition as assessed by dual-energy x-ray absorptiometry (DEXA) and to circulating sex steroid and insulin levels. Serum leptin levels remained significantly higher in women versus men even after adjustment for fat mass, and leptin levels were significantly correlated with fat mass independently of age. By univariate analyses, logarithmically transformed serum leptin levels correlated positively with bioavailable estrogen ([E] estradiol plus estrone) in postmenopausal women not on HRT, and negatively with total and bioavailable testosterone (T) levels in men. Serum insulin levels were directly related to leptin levels regardless of gender and age. By multivariate analyses, fat mass, lean mass, and insulin levels were the strongest predictors of leptin levels in all groups. In addition, bioavailable E entered the model in the postmenopausal women not on HRT. These studies indicate that the fat mass, lean mass, and insulin level are the major determinants of the serum leptin level in adults. Moreover, after adjusting for these variables, bioavailable E also explains a significant proportion of the variance in leptin levels among postmenopausal women not on HRT.

Adult↗

Pharmacological interference with transcriptional control of osteoblasts: a possible role for leptin and fatty acids in maintaining bone strength and body lean mass.

Osteoblasts pass through a sequence of events controlled by hormones and transcriptional factors ensuring proper development of phenotype and functional properties until the osteoblast enter the osteocyte phenotype and/or undergo apoptosis. During its life cycle, the osteoblasts proliferate, deposit matrix proteins and mineralize it until they turn into osteocytes believed to constitute a mechanosensor mesh giving feed-back to the osteoblast to initiate bone modeling or remodeling necessary for the making or remaking of proper bone architecture and strength. It appears that several factors common to osteoblast and adipocyte differentiation determine their entry into different functional stages. Such factors are insulin, growth hormone (GH), insulin-like growth factor type I (IGF-I), transforming growth factor beta (TGFbeta), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), cytokines (e.g. interleukins, interferon and tumor necrosis factor alpha (TNF alpha), bone morphogenetic proteins (BMPs), glucocorticoids, retinoic acid (RA), prostaglandins and cAMP-elevating hormones. The focus of this article is to review the effects of leptin on bone cells and bone turnover, the peroxisome proliferator-activated receptors (PPARs) in the regulation of bone and fat cell differentiation, hormones and fatty acids on the orchestration of osteoblast and adipocyte derived regulatory signals, and mechanostimulation of bone on the mechanisms by which the above mentioned factors modulate osteoblast and adipocyte function. The hypothesis or concept is that prescription of a certain treatment regimen to correct bone turnover, without attempting to assess how hormonal homeostasis, nutritional factors and physical exercise may interact locally, will remain far from optimal, and may even prove detrimental to the patient's health condition.

Adipocytes↗

Influence of heredity and environment on bone density in adolescent boys: a parent-offspring study.

The purpose of the present parent-offspring study was to investigate the influence of heredity and environment on bone density in young men. Another aim was to discover whether the same genetic factors influence bone mass, lean mass and muscle strength. Fifty families including a father, mother and one son were investigated. The mothers (aged 44.5 +/- 4.4 years) and fathers (aged 47.1 +/- 4.4 years) generally had a sedentary lifestyle with little physical activity. As a contrast, all but three of the sons (aged 17.0 +/- 0.4 years) were active in ice hockey training. Bone mineral density (BMD, g/cm2) of the total body, head, lumbar spine and femoral neck was measured using dual-energy X-ray absorptiometry. Muscle strength of the hamstrings and quadriceps muscles was also measured in the boys. BMD values of different sites in the fathers, mothers and sons were adjusted for weight, height, age, and any significant influence of environment. Heritability estimates were obtained as regression coefficients with the boys' adjusted BMD as dependent variable and the adjusted midparent bone density (father BMD + mother BMD/2) as independent variable. Accordingly, heritability explained 34-54% of the variation in the sons' BMD. Midparent BMD of several sites also predicted the boys' lean mass and quadriceps strength, and midparent-offspring differences in lean mass predicted midparent-offspring differences in BMD of the total body, head and spine (beta = 0.30-0.51, p < 0.05). The sons were found to have almost 30% higher femoral neck BMD than their fathers, and physical activity (hours/week) predicted BMD at several sites among the sons beta = 0.26-0.34, p < 0.05). In conclusion, heritability is a main determinant of the variance in BMD in young men. Based on the results we suggest that the same genetic factors may influence bone mass, lean mass and muscle strength by affecting body size. The present study also emphasizes the importance of physical activity for the development and maintenance of BMD in men.

Adolescent↗

Fat mass rather than muscle strength is the major determinant of physical function and disability in postmenopausal women younger than 75 years of age.

OBJECTIVE: Few studies have investigated the relationships between body composition, functional ability, and age-related disability in postmenopausal women. We investigated the relative role of fat mass, lean mass, and muscle strength in the development of disability in a group of healthy postmenopausal women younger than 75 years. DESIGN: We performed a cross-sectional study among 396 independently living women aged 56-73 years, randomly selected between 8 and 30 years after menopause. Lean mass and fat mass were assessed by dual-energy x-ray absorptiometry. Muscle strength (grip and leg extensors) was assessed using dynamometry. Functional ability was estimated by Physical Performance Score, physical activity during the preceding year, and impairment in activities of daily living. RESULTS: Of the participants, 43.7 % were overweight (25 > or = BMI < 30 kg/m2), and 17.7% were obese (BM I > or = 30 kg/m2). Higher muscle strength was observed with increasing lean body mass, and participants with higher muscle strength scored better in the physical performance score and activities of daily living. Higher fat mass was significantly associated with a lower physical performance score, lower physical activity, and a higher frequency of disability. Increasing fat mass was associated with increasing lean mass and decreasing lean/fat ratio. The increase in lean mass and muscle strength associated with higher fat mass was mainly localized in the legs. CONCLUSIONS: Our results support the role of fat mass as the primary risk marker for disability, which might later accelerate by the age-related decrease in lean mass and the development of sarcopenia after the age of 75 years.

Absorptiometry, Photon↗

Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass.

Genetic and pharmacological studies have defined a role for the melanocortin-4 receptor (Mc4r) in the regulation of energy homeostasis. The physiological function of Mc3r, a melanocortin receptor expressed at high levels in the hypothalamus, has remained unknown. We evaluated the potential role of Mc3r in energy homeostasis by studying Mc3r-deficient (Mc3r(-/-)) mice and compared the functions of Mc3r and Mc4r in mice deficient for both genes. The 4-6-month Mc3r-/- mice have increased fat mass, reduced lean mass and higher feed efficiency than wild-type littermates, despite being hypophagic and maintaining normal metabolic rates. (Feed efficiency is the ratio of weight gain to food intake.) Consistent with increased fat mass, Mc3r(-/-) mice are hyperleptinaemic and male Mc3r(-/-) mice develop mild hyperinsulinaemia. Mc3r(-/-) mice did not have significantly altered corticosterone or total thyroxine (T4) levels. Mice lacking both Mc3r and Mc4r become significantly heavier than Mc4r(-/-) mice. We conclude that Mc3r and Mc4r serve non-redundant roles in the regulation of energy homeostasis.

Adipose Tissue↗

Artistic versus rhythmic gymnastics: effects on bone and muscle mass in young girls.

We compared 35 prepubertal girls, 9 artistic gymnasts and 13 rhythmic gymnasts with 13 nonphysically active controls to study the effect of gymnastics on bone and muscle mass. Lean mass, bone mineral content and areal density were measured by dual energy X-ray absorptiometry, and physical fitness was also assessed. The artistic gymnasts showed a delay in pubertal development compared to the other groups (p<0.05). The artistic gymnasts had a 16 and 17 % higher aerobic power and anaerobic capacity, while the rhythmic group had a 14 % higher anaerobic capacity than the controls, respectively (all p<0.05). The artistic gymnasts had higher lean mass (p<0.05) in the whole body and the extremities than both the rhythmic gymnasts and the controls. Body fat mass was 87.5 and 61.5 % higher in the controls than in the artistic and the rhythmic gymnasts (p<0.05). The upper extremity BMD was higher (p<0.05) in the artistic group compared to the other groups. Lean mass strongly correlated with bone mineral content (r=0.84, p<0.001), and multiple regression analysis showed that total lean mass explained 64 % of the variability in whole body bone mineral content, but only 20 % in whole body bone mineral density. Therefore, recreational artistic gymnastic participation is associated with delayed pubertal development, enhanced physical fitness, muscle mass, and bone density in prepubertal girls, eliciting a higher osteogenic stimulus than rhythmic gymnastic.

Anthropometry↗

Is a gene important for bone resorption a candidate for obesity? An association and linkage study on the RANK (receptor activator of nuclear factor-kappaB) gene in a large Caucasian sample.

In light of findings that osteoporosis and obesity may share some common genetic determination and previous reports that RANK (receptor activator of nuclear factor-kappaB) is expressed in skeletal muscles which are important for energy metabolism, we hypothesize that RANK, a gene essential for osteoclastogenesis, is also important for obesity. In order to test the hypothesis with solid data we first performed a linkage analysis around the RANK gene in 4,102 Caucasian subjects from 434 pedigrees, then we genotyped 19 SNPs in or around the RANK gene. A family-based association test (FBAT) was performed with both a quantitative measure of obesity [fat mass, lean mass, body mass index (BMI), and percentage fat mass (PFM)] and a dichotomously defined obesity phenotype-OB (OB if BMI > or = 30 kg/m(2)). In the linkage analysis, an empirical P = 0.004 was achieved at the location of the RANK gene for BMI. Family-based association analysis revealed significant associations of eight SNPs with at least one obesity-related phenotype (P < 0.05). Evidence of association was obtained at SNP10 (P = 0.002) and SNP16 (P = 0.001) with OB; SNP1 with fat mass (P = 0.003); SNP1 (P = 0.003) and SNP7 (P = 0.003) with lean mass; SNP1 (P = 0.002) and SNP7 (P = 0.002) with BMI; SNP1 (P = 0.003), SNP4 (P = 0.007), and SNP7 (P = 0.002) with PFM. In order to deal with the complex multiple testing issues, we performed FBAT multi-marker test (FBAT-MM) to evaluate the association between all the 18 SNPs and each obesity phenotype. The P value is 0.126 for OB, 0.033 for fat mass, 0.021 for lean mass, 0.016 for BMI, and 0.006 for PFM. The haplotype data analyses provide further association evidence. In conclusion, for the first time, our results suggest that RANK is a novel candidate for determination of obesity.

Adult↗

An evaluation of dual-energy X-Ray absorptiometry and underwater weighing to estimate body composition by means of carcass analysis in piglets.

To evaluate the use of dual-energy X-ray absorptiometry (DXA) and underwater weighing (UWW) for body-composition measurements, the carcasses of eight piglets (12-wk old, 15-22 kg in weight) were dissected into muscle, fat and bone. Thereafter, the components were homogenized and chemically analyzed for fat and bone mineral mass. Body components as measured by DXA correlated closely to the carcass analysis (r = 0.90-1.0). However, DXA still overestimated significantly the bone mineral mass, lean mass and total weight, and underestimated fat mass. The reproducibility of measurements, expressed as the CV for fat mass was 13.5%, whereas for total weight, lean mass and bone mineral mass, the CV was 0.74-1.9%. Fat mass was overestimated by UWW using the equations of Siri or Kraybill (r = 0. 77), but not by the equation of Lohman et al. (r = 0.69). The difference between the estimation of fat by chemical analysis and estimations by DXA and UWW was significantly affected by the amount of water in lean mass and fat-free mass.

Absorptiometry, Photon↗

Risk factors for low bone mineral density among females: the effect of lean body mass.

BACKGROUND: This study determines if body composition and lifestyle are risk factors for low radius-bone mineral density (R-BMD) and evaluates the role of body composition in the age-related decline of R-BMD. METHODS: Data on age, menopausal status, fat mass, lean body mass (LBM), drinking, smoking, and occupation were collected from 3,867 females ages 37-69, whose R-BMD was also measured. Multiple logistic regression analyses examined the predictive accuracy of these factors for low (20th percentile) R-BMD. RESULTS: Age, LBM, and menopausal status were risk factors for the 37-55 age group, while age, LBM, and lifestyle (alcohol consumption 3 or fewer days per week and currently smoking) were risk factors for the 56-69 age group. The odds ratio (OR) for LBM was nearly reciprocal to the ORs for age and for menopausal status. Our model has low sensitivity, high specificity, low positive predictive value, and high negative predictive value. CONCLUSIONS: Consumption of alcohol 3 or fewer days per week and being a current smoker have a negative effect on R-BMD among older (56-69) women. The positive effect of LBM on R-BMD continues from age 37 on LBM has an effect almost equal but opposite to those of aging and menopause on the risk of low R-BMD. High LBM after age 37 predicts normal R-BMD.

Adult↗

Hologic QDR 2000 whole-body scans: a comparison of three combinations of scan modes and analysis software.

This study reports on the short-term in vivo precision and absolute measurements of three combinations of whole-body scan modes and analysis software using a Hologic QDR 2000 dual-energy X-ray densitometer. A group of 21 normal, healthy volunteers (11 male and 10 female) were scanned six times, receiving one pencil-beam and one array whole-body scan on three occasions approximately 1 week apart. The following combinations of scan modes and analysis software were used: pencil-beam scans analyzed with Hologic's standard whole-body software (PB scans); the same pencil-beam analyzed with Hologic's newer "enhanced" software (EPB scans); and array scans analyzed with the enhanced software (EA scans). Precision values (% coefficient of variation, %CV) were calculated for whole-body and regional bone mineral content (BMC), bone mineral density (BMD), fat mass, lean mass, %fat and total mass. In general, there was no significant difference among the three scan types with respect to short-term precision of BMD and only slight differences in the precision of BMC. Precision of BMC and BMD for all three scan types was excellent: < 1% CV for whole-body values, with most regional values in the 1%-2% range. Pencil-beam scans demonstrated significantly better soft tissue precision than did array scans. Precision errors for whole-body lean mass were: 0.9% (PB), 1.1% (EPB) and 1.9% (EA). Precision errors for whole-body fat mass were: 1.7% (PB), 2.4% (EPB) and 5.6% (EA). EPB precision errors were slightly higher than PB precision errors for lean, fat and %fat measurements of all regions except the head, although these differences were significant only for the fat and % fat of the arms and legs. In addition EPB precision values exhibited greater individual variability than PB precision values. Finally, absolute values of bone and soft tissue were compared among the three combinations of scan and analysis modes. BMC, BMD, fat mass, %fat and lean mass were significantly different between PB scans and either of the EPB or EA scans. Differences were as large as 20%-25% for certain regional fat and BMD measurements. Additional work may be needed to examine the relative accuracy of the scan mode/software combinations and to identify reasons for the differences in soft tissue precision with the array whole-body scan mode.

Absorptiometry, Photon↗

[Effect of anticancer treatment on leptin level, fat body mass (FM) and lean body mass (LBM)].

UNLABELLED: Leptin plays an important role in the metabolism of adipose tissue. Considering that malignancy and its treatment cans affect normal development in childhood. We analysed the correlations between serum leptin levels and body composition after anticancer treatment. We studied 33 survivors (24 boys and 9 girls) who before our study, have been treated for acute lymphoblastic leukaemia (ALL) (n=23) and Hodgkin disease (n=10) after 7.15+/-3.5 years. Sixteen patients with ALL received cranial irradiation (12Gy). We measured body mass index (BM1) fat mass (FM) and lean body mass (LBM) using dual energy x-ray absorptiometry (DXA). We compared these results to the results obtained from reference values (SD score). Leptin levels were measured with the RIA method. RESULTS: 1. Mean leptin levels were higher in girls after puberty (10.93 ng/mL+/-8.9) than in boys (3.73 ng/mL+/-3. 7). In boys no differences were found in leptin levels between T2-4 and T5 stages. In girls the leptin values increased after puberty. Leptin SD score levels were higher in boys during (1.55 +/-1.0) and after puberty (1.46+/-0.75) and in girls - after puberty (1.19 +/-1.51). We did not find any influence of cranial irradiation (12Gy) or various methotrexate doses (5 g/m(2) vs. 19/m(2)) leptin values. 2. No difference in BMI SD score was found within the whole study group. 3. FM did not change ill boys during and after puberty, although FM SD score were higher during puberty (2.98 +/-4.8). In girls FM and FM SD score were higher after puberty. In boys and girls LBM augmented with pubertal development but LBM SD score in boys were lower after puberty (-1.67 +/-1.7) in comparison to puberty (0.2 +/-1.7). No differences were found between LBM SD score in girls during and after puberty. 4. We found a correlation between leptin levels and BMI (r=0.59 p=0.001) and FM (r=0.77 p=0.0001). 5. Relation of FM to LBM in boys remained unchanged, however in girls it increased within pubertal development. CONCLUSION: l. Anticancer treatment during childhood shows no influence on body mass index although the tendency to higher fat mass in pubertal boys and in post pubertal girls is observed. 2. Leptin values depend on fat mass and do not relate directly to the pubertal stage.

Absorptiometry, Photon↗

Relationship between measures of body size and composition and velocity of lactate threshold.

The purpose of this investigation was to explore the relationship between velocity of lactate threshold (vLT) and various measures of body mass and composition: mass, lean mass, fat mass, percent body fat (% fat), and body surface area (BSA). We hypothesized that mass would be inversely related to vLT, and that differences in measures of body mass and composition would account for a significant amount of variability in vLT. A total of 21 healthy male runners served as subjects. Body composition was assessed by hydrostatic weighing. A significant negative relationship (r = -0.759, p < or = 0.01) was between body mass and vLT. The coefficient of determination between vLT and body mass indicated that nearly 58% of the variability in vLT was explained by body mass in these subjects. Significant relationships were also between vLT and BSA (r = -0.72, p < or = 0.01), fat mass (r = -0.70, p < or = 0.01), % fat (r = -0.59, p < or = 0.01), and lean mass (r = -0.41, p < or = 0.05). Linear regression yielded the following model: y = 369.48 - 1.7343 (X), where y = predicted vLT (m.min(-1)) and X = body mass (kilograms) (SEE = 15.45). Velocity of lactate threshold was significantly inversely related with body mass in a group of male runners. The calculated coefficient of determination suggests that nearly 58% of the variability in vLT was explained by body mass. The present data suggest consideration of categorizing participants in 'road runs' by body mass to equate competition, as is done in other sports (e.g., weightlifting).

Adult↗

Relationship between red cell mass, body weight, lean body mass, and body cell mass in growing pigs and beagles.

During growth in 55 pigs (from birth through week 12) and 42 beagles studied (from birth through year 1), there was an equally close association between red cell mass (RCM) and body weight, lean body mass (LBM) and body cell mass (BCM); the coefficients of correlation were between 0.94-0.99. The association of RCM with body weight was the result of BCM, extracellular tissue (ECT), and fat, each increasing at a constant rate relative to body weight. The primary relationship appears to be between RCM, the oxygen-delivery system, and BCM, the principla oxygen-using system; and the close association of RCM with body weight and LBM the results of the growth patterns of their components.

Animals↗

Social inhibition of seasonal fattening in wild and captive gray mouse lemurs.

Due to their differential reproductive investment, males and females often exhibit high differences in energy management. The main hypothesis tested in this study is that short photoperiod-induced fattening in the small primate Microcebus murinus is strongly affected by social cues. Short photoperiod-induced changes in body mass, lean mass and thyroid hormone T4 plasma levels measurements were investigated in wild and captive animals. Individual housing showed that both males and females are able to fatten. Fattening was associated with a slight increase of lean mass that reached a plateau after 3 weeks. In contrast, social grouping led to an inhibition of fattening, even when direct interactions were prevented. This social inhibition was mainly observed in males, especially when housed with females, suggesting that their low weight gain in the wild is due to female dominance. Accordingly, wild and captive animals of both sexes exhibited a decrease in T4 plasma levels, revealing a decrease in energy expenditure. Moreover, testis recrudescence observed after 20 weeks of short photoperiod exposure did not lead to any inhibition of fattening, indicating that males take advantage of female hibernation late in the dry season to fatten and use their fat reserves for the mating competition. Therefore, seasonal fattening may be used by females to prepare for hibernation and by males to prepare for the mating competition.

Analysis of Variance↗