Birth weight and body composition in young adult men--a prospective twin study.

OBJECTIVES: To evaluate the association between birth weight and adult body composition in twins, controlling for maternal and genetic influences. DESIGN: Twins were randomly selected from the East Flanders Prospective Twin Survey, a population-based historic twin cohort. SUBJECTS: Male members of 229 twin pairs between 18 and 34 y of age who participated in the Prenatal Programming Twin Study. MEASUREMENTS: Adult body mass, height, BMI, lean body mass, sum of skinfolds and waist-to-hip-ratio. Lean body mass, sum of skinfolds and waist-to-hip-ratio were also adjusted for body mass. Intra-pair difference in adult anthropometric measures between the heaviest and the lightest twin at birth. RESULTS: Per kg increase in birth weight, body mass (4.2 kg), height (3.3 cm), lean body mass (3.1 kg) and to a lesser extent BMI (0.49 kg/m(2)) increased, whereas waist-to-hip-ratio (-1.4%) and sum of skinfolds (-0.11 s.d.) decreased, when adjusted for body mass. In a pair-wise analysis, the heavier twin at birth was taller and heavier as an adult, but, when adjusted for body mass, he had a lower waist-to-hip-ratio, less subcutaneous fat, and more lean body mass, compared to his lighter sib. Intra-pair difference in body composition was associated with intra-pair birth weight difference in monozygotic and dizygotic twins. CONCLUSIONS: An adverse intra-uterine environment, as measured by birth weight, is associated with more subcutaneous and abdominal fat and less lean body mass in adulthood. This association is independent of maternal and genetic influences. However, we cannot exclude the existence of genes that act on both birth weight and adult body composition.     

Sleeping metabolic rate in relation to body mass index and body composition

OBJECTIVES: To determine whether patterns of sleeping metabolic rate (SMR) are altered in obesity. Specifically to determine the relationship between changes in SMR and body weight, body mass index (BMI, kg/m(2)), and fat-free mass (FFM); and to compare resting metabolic rate (RMR) with SMR during different periods of sleep. SUBJECTS: Eighteen healthy, pre-menopausal, obese (BMI >30, n=9) and non-obese (BMI <30, n=9), female subjects (six Caucasians and 12 African-Americans), with an average age of 36 y (range 22-45). MEASUREMENTS: Total energy expenditure (TEE or 24 h EE), metabolic rate (MR), SMR (minimum, average and maximum) and resting metabolic rate (RMR) or resting energy expenditure (REE) measured by human respiratory chamber, and external mechanical work measured by a force platform within the respiratory chamber. Physical activity index (PAL) was derived as TEE/REE. Body composition was determined by dual-energy X-ray absorptiometry (DXA). RESULTS: SMR decreased continuously during sleep and reached its lowest point just before the subject was awakened in the morning by the research staff. Although averages for RMR and SMR were similar, RMR was lower than SMR at the beginning of the sleeping period and higher than SMR in the morning hours. The rate of decrease in SMR was faster with increasing body weight (-0.829, P<0.0001), BMI (correlation factor -0.896, P<0.0001) and FFM (-0.798, P=0.001). The relationship between the slope of SMR decrease and BMI (y=-5 x 10(-6)x(2)+0.0002x-0.0028) is highly significant, with a P-value of <0.0001 and r(2) value of 0.9622. CONCLUSIONS: The rate of decline in metabolic rate during sleep is directly related to body weight, BMI and FFM. Average SMR tends to be lower than RMR in obese subjects and higher than RMR in non-obese subjects.     

Cord blood leptin concentrations in relation to intrauterine growth

OBJECTIVE: Leptin, a hormone that signals the amount of energy stores to the brain, has recently been shown to play a role in the regulation of several hypothalamic pituitary axes, including the growth hormone axis. To investigate a potential association between cord blood leptin concentrations and intrauterine growth we measured leptin concentrations in the cord blood of small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) healthy newborns. PATIENTS AND MEASUREMENTS: Cord blood leptin concentrations were evaluated in 25 SGA, 100 AGA, and 45 LGA, neonates. RESULTS: Leptin was detectable in all newborns in concentrations comparable with those found in adults. Moreover, SGA newborns had lower leptin concentrations (3.70 +/- 1.81 micrograms/l) than AGA (5.65 +/- 4.98 micrograms/l) and LGA newborns (11.99 +/- 7.06 micrograms/ l)(P < 0.01). Cord blood leptin concentrations were significantly associated with ponderal index, cord blood insulin concentrations, placental weight and maternal serum leptin concentrations. Importantly, the association between cord blood leptin concentrations and intrauterine growth status persisted after adjusting for adiposity, placental weight, maternal serum leptin concentrations and cord blood insulin concentrations. CONCLUSIONS: Cord blood leptin concentrations are independently associated with intrauterine growth. Future studies are needed to elucidate the underlying mechanism and clarify the role of leptin in regulating growth and controlling appetite in newborns.     

Intrauterine programming of adult body composition

Epidemiological studies suggest an association between weight in infancy and the risk of osteoporosis in later life. The extent to which this reflects environmental influences on skeletal growth and metabolism before birth or during the first year of postnatal life remains uncertain. We therefore examined the association between birth weight and adult body composition (bone, lean, and fat mass) in a cohort of 143 men and women, aged 70-75 yr, who were born in Sheffield, UK, and still lived there. The subjects underwent assessment of body composition by dual energy x-ray absorptiometry. Neonatal anthropometric information included birth weight, birth length, head size, and abdominal circumference. There were significant (P < 0.01) positive associations between birth weight and adult, whole body, bone, and lean mass among men and women. These were mirrored in significant (P < 0.03) associations between birth weight and bone mineral content at the lumbar spine and femoral neck. Associations between birth weight and whole body fat were weaker and not statistically significant. The associations of birth weight with whole body bone mineral and lean mass remained statistically significant after adjustment for age, sex, and adult height. They also remained significant after adjustment for cigarette smoking, alcohol consumption, dietary calcium intake, and physical inactivity. These data are in accord with previous observations that anthropometric measures in infancy are associated with skeletal size in adulthood. The presence of these relationships at birth adds to the evidence that bone and muscle growth may be programmed by genetic and/or environmental influences during intrauterine life.     

The contribution of genes, environment and of body mass to blood pressure variance in young adult males

OBJECTIVE: (1) To determine by means of multivariate genetic modelling whether the covariation of blood pressure (BP) and body mass index (BMI) is compatible with a direct effect of BMI on BP, or rather with pleiotropy or environmental association, and (2) to quantify the contribution of such an effect and of heritability and environmental factors to BP variance. DESIGN AND METHODS: Fifty monozygous and 41 dizygous male twin pairs (ages: 17-38 years) were studied. BMI was calculated as weight/height. Blood pressure was the mean of three conventional measurements in the supine position. Estimates for the path coefficients of the three hypothesised models were obtained using Maximum Likelihood Estimation and were used to calculate the predicted covariance matrices for these models. A chi2 goodness-of-fit index of P>0.05 indicated an adequate fit. Likelihood ratio chi2 statistics and the Akaike Information Criterion (AIC) were used to choose the best model among the fitting models. The path coefficients of the best model were used to estimate the variance decomposition of BP. RESULTS: All hypothesised models fitted the data. The AIC was lowest for the model representing an influence of BMI on BP, for both systolic (AIC = -22.3) and diastolic (AIC = -22.2) BP. The estimated percentages of the total phenotypic variance of BP, which could be explained by the influence of BMI on BP, were 11.4% and 12.9% for systolic and diastolic pressure respectively. The remaining variances were associated with variation in genetic and environmental factors. CONCLUSIONS: A direct influence of BMI on BP constitutes the most likely explanation of the BP-BMI-covariation and it accounts for about 12% of the BP-variance in young healthy men.     

Heritability of plasma sex hormones and hormone binding globulin in adult male twins

Plasma sex hormone concentrations have been used as biomarkers in epidemiological studies of many conditions including cancer, obesity, bone density, and coronary heart disease. The objective of this analysis was to estimate genetic and nongenetic influences on endogenous sex hormones (testosterone, estradiol, estrone, and SHBG) in a large sample of 532 adult white male twins (134 monozygotic and 132 dizygotic twin pairs) from the National Heart, Lung, and Blood Institute Twin Study. Participants were aged 59-70 yr at the time of plasma collection, and hormone concentrations were determined with RIA. Genetic models were fitted by the method of maximum likelihood. Testosterone and SHBG concentrations have substantial genetic variation, with additive genetic factors accounting for 57 and 68% of the total phenotypic variation, respectively. In contrast, variation in estrone (37% shared environmental and 63% individual specific environmental effects) and estradiol concentrations (25% genetic effect, 44% shared environmental effects, and 31% individual specific environmental effects) were largely influenced by nongenetic factors. Assessment of the relative contribution of genetic and nongenetic influences on hormone concentrations may help in the search for genes underlying variation and covariation in complex traits affected by plasma sex hormone concentrations.     

Sex differences in the relation of body composition to markers of inflammation

OBJECTIVE: It has been suggested that low-grade systemic inflammation is associated with obesity and that this association might be modified by sex. METHODS AND RESULTS: We performed a cross-sectional analysis among 641 men and 597 women aged 55-74 years who participated in the population-based KORA Survey 2000, conducted in the area of Augsburg, Germany. Measures of both total (fat mass, body mass index) and abdominal adiposity (waist circumference (WC), waist to hip ratio (WHR)) were highly correlated with markers of systemic inflammation (C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen (FIB), interleukin-6 (IL-6)) in men and in women. Significant associations persisted when the effect of lifestyle factors was taken into account. In multivariable linear regression analysis, a considerably higher percentage of variability in inflammatory markers was explained by body composition in women compared to men. Furthermore, the relevance of single body composition variables varied by sex. In women, fat mass in % explained the highest percentage of the variability of circulating acute-phase proteins (18.2% for CRP, 7.2% for SAA, 6.1% for FIB, all p-values < 0.001), whereas in men, WHR explained the highest percentage of the variability (6.2% for CRP, 2.3% for SAA, 1.8% for FIB, all p-values < 0.001). For IL-6, WC explained the highest percentage of the variability in women (3.7%, p < 0.001) and in men (1.8%, p < 0.001). CONCLUSION: Adiposity is strongly associated with low-grade systemic inflammation in men and in women but the association is considerably stronger in women, especially for CRP. Thus, weight reduction as a means to prevent a state of subclinical inflammation might be particularly effective in women.     

Early childhood predictors of adult body composition

Intra-uterine life has been identified as a possible critical period for the development of obesity risk in both adults and children; others have highlighted the importance of growth and nutrition in the first few years. It is suggested that fetal growth, as assessed by birth weight, may programme lean body mass later in life. Children who are born small for gestational age also have a predisposition to accumulating fat mass, particularly intra-abdominal fat. It is not yet clear whether this predisposition is due to their prenatal growth restraint, their rapid postnatal catch-up growth or a combination of both. Recently, genetic and heritable factors have been shown to contribute to both rapid postnatal growth and childhood obesity risk in children and adults. Future studies should explore their timing of action and potential interactions with markers of antenatal growth restraint.     

Testosterone, sex hormone-binding globulin, and body composition in young adult African American and Caucasian men

This study examined the diurnal variation in circulating total and free testosterone and sex hormone-binding globulin (SHBG) levels in young adult African American and Caucasian men in order to investigate whether there are differences in the secretion of these plasma hormones in populations at different risks of developing prostate cancer as they age. A significant and similar diurnal rhythm for total and free testosterone was found for both groups. Serum levels of total testosterone were 29.4% and 23.9% lower at 8:00 PM than at 8:00 AM in African American and Caucasian men, respectively. Significantly higher serum levels of total testosterone (P<.01) and SHBG (P <.02) were found in the African American than in the Caucasian men in both the morning and evening, whereas free testosterone levels were similar in both groups. The higher SHBG levels appear to have an environmental/metabolic basis in that the waist circumference, waist-to-hip ratio, and fasting insulin concentration were lower (P <.05) in African Americans than in Caucasians. In summary, these data indicate that racial differences in central adiposity in men are established in early adulthood and influence circulating SHBG and thereby testosterone levels. In light of the findings by others that SHBG increases cyclic adenosine monophosphate (cAMP) production in the prostate and that cAMP-dependent protein kinase A is a coactivator of the androgen receptor, these studies provide a possible mechanism by which circulating androgens may contribute to the increased risk for prostate cancer among African American men.     

Combined effects of oral oleoyl-estrone and limited food intake on body composition of young overweight male rats

OBJECTIVE: The combined effects of limited food intake and OE treatment have been analysed in order to determine whether hypocaloric diets enhance the slimming effects of OE on mature overweight male rats. Two levels of dietary limitation at 50 and 25% of a standard intake were established, roughly corresponding to the human LCDs and VLCDs. DESIGN: Wistar male rats (6 weeks old) were made overweight by a cafeteria diet. After transition to standard diet, they were subjected to food restriction: down to 50 or 25% with respect to the transition period. Half the animals were given daily oral gavages of 10 nmol/g oleoyl-estrone (OE), and the rest received only the vehicle during 10 days. MEASUREMENTS: Changes in weight and body composition: water, lipid, protein or gross energy were determined by comparing the final pool size with that of day 0, calculated from the initial body weight and the composition of untreated rats. Energy and nitrogen balances were estimated. Plasma levels of metabolites and hormones were also measured. RESULTS: OE induced changes in body composition similar to those elicited by a 50% reduction in food, with massive loss of lipid and energy. OE-treated rats ate less than the controls, but additional effects on body composition on reduced diet were minimal. OE improved metabolic homoeostasis: better maintained glycaemia, lower cholesterol and shallower hormonal changes, but at the expense of slightly increased protein mobilisation. CONCLUSIONS: The data presented suggest that no advantages are accomplished by combining OE treatment and hypocaloric diets compared with OE alone, at least under the experimental conditions tested, since the effects were not additive. Despite OE affecting food intake, mechanisms other than that are deemed responsible for the mobilisation of body fat, since intake alone cannot explain the effects on body weight, nor the metabolic and hormonal changes in OE-treated rats. It is concluded that the combination of food restriction and OE may result in unwanted increased protein mobilisation with no synergy between both slimming treatments.     

Comparison of regional body composition and its relation with cardiometabolic risk between BMI-matched young and old subjects

ObjectiveDifference in regional body composition between young and old people may be related with differential cardiometabolic risks. We investigated regional body composition in BMI-matched young and old subjects to compare its relation with cardiometabolic risk.MethodsWe recruited 1:3 gender- and BMI-matched 86 young subjects (mean age 27.3 ± 2.9 years) and 258 older subjects (75.6 ± 8.2 years) from a community. Abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) and muscle area at mid-thigh level were evaluated by computed tomography. Fat depots in the gynoid area and lower extremity were measured by dual energy X-ray absorptiometry. Adiponectin, retinol binding protein-4 (RBP-4), and C-reactive protein (CRP) concentrations, pulse wave velocity (PWV) and ankle-brachial index (ABI) were measured for cardiometabolic risk.ResultsVAT was greater in older subjects while SAT was almost the same, resulting in twice higher VAT/SAT ratio in older men and women (1.03 ± 0.37 and 0.57 ± 0.18) than younger counterparts (0.55 ± 0.24 and 0.23 ± 0.23) (both P < 0.01). Fat mass in the gynoid area and lower extremity was smaller in older subjects than younger subjects. The VAT correlated with adiponectin level negatively and RBP-4 level positively while gynoid fat correlated with them in opposite direction. The CRP levels negatively correlated with mid-thigh muscle in older subjects. Older subjects had higher PWV and lower ABI compared to BMI-matched younger counterparts.ConclusionIn conclusion, older adults in this cohort had increased visceral fat and decreased gynoid and lower extremity fat, along with less muscle mass. These findings may help explain the worse cardiometabolic profiles in the elderly who have the same BMI as the young.     

Plasma leptin levels in relation to body composition and body fat distribution in patients with Cushing's syndrome

It is known that body composition, especially body fat content, determines plasma leptin (LEP) levels. Clinical observation confirms that glucocorticoids (GS) have a considerable impact on body composition and body fat distribution which leads to visceral fat accumulation and a decrease in muscle mass in limbs. On the other hand, in experimental models GS stimulate ob mRNA expression in adipose tissue and LEP secretion into bloodstream. The aim of the study was to evaluate changes in body composition and fat and fat-free mass distribution in the conditions of endogenous hypercortisolism as well as to determine whether changes in body composition parameters may influence plasma LEP levels in patients with Cushing's syndrome (CUS). The study group was composed of 14 patients (12 F, 2 M) with ACTH-dependent and ACTH-independent CUS (BMI 29,5 +/- 1,0 kg/m2, aged 41,6 +/- 2,9 yrs.). The control group (KON) included 14 overweight/obese subjects (12 F, 2 M; WHR>0.8) matched for age, height, weight, and BMI with CUS group. Basal plasma LEP levels were measured by RIA kit. Total fat mass (BFM), fat-free mass (FFM), their regional depots (arms, legs, trunk) as well as bone mineral content (BMC) were determined by DEXA method (Lunar Co., USA). Values of BFM and %BF were comparable in both groups whereas the amount of FFM was lower in CUS group than in controls. Patients with CUS had less BF in limbs than controls whereas the difference in the amount of trunk BF in favour of CUS reached a borderline significance. Moreover, subjects with CUS exhibited decreased amount of FFM both in arms and legs when compared to controls, which may be explained by limb muscle and connective tissue wasting observed clinically. However, the amount of trunk FFM did not differ between both groups. Eventually, subjects with CUS had lower BMC values than controls. Absolute plasma LEP levels were 2-fold higher in CUS group than those in KON group (34,03 +/- 4,45 vs. 17,04 +/- 1,88, ng/ml; p=0.006), however, in both groups they were highly correlated with BFM and %BF. Multiple linear regression analysis revealed that in CUS group 64% of the variation of plasma LEP levels is explained by trunk BF and in KON group 92% of the variation of LEP levels is dependent of arms BF (+, 18%) and legs BF (+, 69%) and arms FFM (-, 5%). In conclusion, endogenous hypercortisolismus leads to the augmentation of truncal (visceral) fat accumulation as well as to a marked decrease in fat-free mass in limbs and in bone mineral content. In Cushing's syndrome, irrespectively of its cause (pituitary gland, adrenal glands), plasma LEP levels are elevated in relation to body fat content. Truncal (visceral) fat may have a relatively stronger influence on plasma LEP in Cushing's syndrome than in subjects with normal cortisolaemia, however, changes in body composition and tissue distribution do not fully account for the presence of markedly elevated LEP levels in this syndrome.     

Genomic imprinting effects on adult body composition in mice

Genomic imprinting results in the differential expression of genes, depending on which allele is inherited from the mother and which from the father. The effects of such differential gene expression are reflected in phenotypic differences between the reciprocal heterozygotes (Aa vs. aA). Although many imprinted genes have been identified and play a key role in development, little is known about the contribution of imprinting to quantitative variation in trait expression. Here, we examine this problem by mapping imprinting effects on adult body composition traits in the F(3) generation of an intercross between the Large (LG/J) and Small (SM/J) inbred mouse strains. We identified eight pleiotropic imprinted quantitative trait loci (iQTL) located throughout the genome. Most iQTL are in novel locations that have not previously been associated with imprinting effects, but those on chromosomes 7, 12, and centromeric 18 lie in regions previously identified as containing imprinted genes. Our results show that the effects of genomic imprinting are relatively small, with reciprocal heterozygotes differing by approximately 0.25 standard deviation units and the effects at each locus accounting for 1% to 4% of the phenotypic variance. We detected a variety of imprinting patterns, with paternal expression being the most common. These results indicate that genomic imprinting has small, but detectable, effects on the normal variation of complex traits in adults and is likely to be more common than usually thought.     

Size at birth and its relation to muscle strength in young adult women

OBJECTIVE: To assess the relationship between development in utero, assessed by birth weight, and muscle strength in young adult women as assessed by grip strength. METHODS: A total of 1563 participants aged 20-40 years in the Southampton Women's Survey had their grip strength measured during pregnancy. At recruitment to the survey the women had been asked to recall their birth weight or obtain it from their parents. For 536 women born in Southampton, birth weight was obtained from hospital records. Grip strength was related to birth weight using multiple linear regression analysis, adjusting for age, height, weight and reported physical activity. RESULTS: Grip strength increased with age, height, weight, physical activity and birth weight. In the mutually-adjusted model, grip strength increased by 1.10 kg per kilogram of birth weight (95% CI: 0.58-1.61 kg). In women with hospital birth weight data the relationship strengthened to 1.44 kg per kilogram of birth weight (95% CI: 0.50-2.38 kg). CONCLUSIONS: Grip strength in women in their twenties and thirties is at or approaching its peak. The association between grip strength and birth weight was remarkably similar to findings from other studies of women at younger and older ages. This indicates that in utero development has consequences for muscle strength throughout the life course, even allowing for the increase to peak muscle strength and then its decline as a woman ages.