Effects of gender, body composition, and menopause on plasma concentrations of leptin

Circulating concentrations of leptin ([leptin]) vary directly with body mass index and percentage body fat, and may thus constitute an afferent limb of a system regulating body fatness. We tested the hypotheses that: 1) Plasma [leptin] vary more directly with absolute fat mass than with fractional body fatness per se: and 2). The relationship between fat mass and [leptin] is significantly affected by gender and by menopausal status. [Leptin] in the post-absorptive state was examined in 67 subjects (26 male, 20 premenopausal female, 21 postmenopausal females; 43 never-obese, 24 obese) at usual body weight. Body composition was determined by hydrodensitometry, and [leptin] was determined by a double antibody ELISA assay. In male and pre-menopausal female subjects, subcutaneous adipose tissue aspirations were performed for determination of adipocyte volume by the osmium fixation method, and a 3 hour oral glucose tolerance tests was performed. At usual body weight, ([leptin]) was better correlated with absolute fat mass than with body mass index (BMI) or percentage body fat. BMI and % body fat did not account for any of the variance in [leptin] beyond that attributable to FM, per se. The regression equations relating FM to [leptin] did not differ significantly between obese and never-obese subjects. [Leptin] and fasting serum insulin concentrations were significantly correlated in males only. [Leptin] was significantly higher in pre- and post-menopausal females compared to males, even when [leptin] was corrected for differences in body composition (pre-menopausal females > post-menopausal females > males). While plasma [leptin], corrected for FM, declines significantly in women post-menopause, this decline is not sufficient to account for the striking sexual dimorphism in the relationship of leptin to fat mass. This sexual dimorphism is apparently also due, in part, to a suppressive effect of circulating androgens on [leptin].     

Sex hormones, body fat distribution, resting metabolic rate and glucose-induced thermogenesis in premenopausal obese women

The topographic specificity of upper body obesity is known to be at the origin of a series of metabolic complications. In contrast to this negative effect, women with abdominal obesity usually can lose more body weight than women with gluteal-femoral obesity. In order to find some contributive explanations for this effect, we studied resting metabolic rate (RMR) and glucose-induced thermogenesis (GIT) in both types of obesity. Since upper body obesity is characterized by androgen excess, a relationship between body fat distribution, sex hormones, RMR and indices of thermogenesis was studied. Of 39 obese women who were recruited (mean age: 32.4 +/- 9.3 years), 30 were compared for analysis. Upper body obesity (waist-to-hip ratio (WHR): 0.84 +/- 0.02; body mass index (BMI) 36.2: 36.2 +/- 6.0) is not characterized by differences in RMR, whereas glucose-induced thermogenesis is significantly higher in this subgroup (P < 0.008), expressed as percentage increase above RMR (18.3 +/- 8.5 vs. 11.9 +/- 3.6%) or as percentage of metabolisable energy intake (8.2 +/- 3.3 vs. 5.8 +/- 2.3%). Correlation coefficient data show that GIT determinants are closely related to WHR (r = 0.43; P < 0.01) and not to BMI. Resting metabolic rate, both in absolute terms and corrected for fat-free mass (FFM), is not related to indices of androgenicity, but is negatively related to serum oestradiol levels; this negative relationship with oestradiol disappears when RMR is corrected for both fat mass (FM) and FFM. GIT parameters are not related to free testosterone or oestradiol, regardless of the phase of the menstrual cycle.(ABSTRACT TRUNCATED AT 250 WORDS)     

The pattern of maternal serum inhibin-A concentrations in the second trimester of pregnancy

Maternal serum inhibin-A concentration is a useful marker in prenatal screening for Down syndrome in the second trimester. We measured inhibin-A concentrations in 4304 pregnancies without Down syndrome between 14 and 22 weeks of pregnancy to determine the median values according to gestational age. There was a U-shaped pattern of inhibin-A concentration against gestational age with a minimum concentration at 17 weeks and 1 day (120 days). We suggest that screening centres use a quadratic equation when estimating their normal median inhibin-A level, constraining the shape of the curve and fixing the lower point of the curve to occur at 120 days, but allowing its position in relation to the vertical inhibin-A axis to be set according to the local data. This approach will systematically allow for the changing inhibin-A concentration without introducing the instability of deriving a fresh quadratic equation for each screening centre and each time a centre's medians are revised.     

Sympathetic nervous system activity and resting metabolic rate in vegetarians

We examined the resting metabolic rate (RMR) and sympathetic nervous system activity of young male vegetarians (n = 17) and nonvegetarians (n = 40). Subjects were characterized for RMR by indirect calorimetry, norepinephrine kinetics from infusions of tritiated norepinephrine, energy and macronutrient intake from a 3-day food diary, and body composition by underwater weighing. Vegetarians reported a greater relative intake of carbohydrates (62% +/- 5% v 51% +/- 6%, P < .01) and a lower relative intake of fat (25% +/- 5% v 33% +/- 6%, P < .01) than nonvegetarians, whereas no differences were observed in daily energy intake, body composition, or maximal aerobic capacity (VO2max) between groups. Vegetarians exhibited an 11% higher absolute RMR (1.29 +/- 0.15 v 1.16 +/- 0.13 kcal/min, P < .01), a higher plasma concentration of norepinephrine (216 +/- 33 v 165 +/- 18 pg/mL, P < .01), and a greater norepinephrine appearance rate (0.50 +/- 0.08 v 0.36 +/- 0.09 micrograms/min, P < .01) than nonvegetarians. After statistically controlling for differences in relative amounts of carbohydrate and fat in the diet and for norepinephrine concentrations, no significant differences in adjusted RMR between vegetarians and nonvegetarians were noted. These results suggest that the higher RMR observed in young male vegetarians is partially mediated by differences in dietary macronutrient composition and increased sympathetic nervous system activity.     

Increase in serum leptin and uterine leptin receptor messenger RNA levels during pregnancy in rats

Pregnancy is a physiological state associated with significant changes in appetite, thermogenesis, and lipid metabolism, functions which are regulated in part by a hormone, leptin, secreted by adipocytes. Leptin has also been shown to have a role in reproduction, promoting centrally-regulated maturation of the reproductive system and signaling the presence of adequate maternal energy stores for fertility. Here we demonstrate that serum leptin levels are modulated during normal rat pregnancy with a 1.8-fold increase during pregnancy followed by a decrease just before parturition. Leptin receptor mRNA levels in the uterus are also regulated with an increase about 2.7-fold during this same period, whereas there is no change in other tissues examined. The results suggest that leptin may play a role during pregnancy, perhaps regulating energy utilization.     

Serial changes in body composition throughout adulthood and their relationships to changes in lipid and lipoprotein levels. The Fels Longitudinal Study

Few studies have examined the relationships between measures of body composition and lipid and lipoprotein levels in long-term serial data from individuals unselected for cardiovascular disease- or obesity-related variables, and none have considered such extensive serial data as used in the current study. The aim was to examine in such individuals the associations between annual changes in lipid and lipoprotein levels and concurrent changes in total body fat, fat-free mass, percent body fat, and body mass index. Serial data from 1304 examinations of 423 adult white participants in the Fels Longitudinal Study were analyzed sex-specifically in 2 age groups, 18 through 44 years and 45 to 65 years. A regressive analytic approach utilized the long-term (4 to 20 years) serial data of individuals. Annual changes in adiposity, independent of levels of lean tissue changes, before and after age 45 for men and women were significantly correlated with corresponding annual changes in cholesterol and low density lipoprotein cholesterol. In men before age 45, changes in triglycerides and high density lipoprotein cholesterol were also significantly associated with changes in adiposity, with the relationship remaining after age 45 in high density lipoprotein cholesterol. Increases in adiposity in individuals are associated with changes in lipid and lipoprotein levels in the direction of increased risk for cardiovascular disease. Adult levels of total cholesterol and low density lipoprotein cholesterol across age and sex and high density lipoprotein cholesterol in men are responsive to changes in adiposity, independent of initial adiposity or lipid and lipoprotein levels.     

Menopausal changes in body composition and energy expenditure

Adult American women as a group tend to gain weight with age, and many women report that their weight gain started around the time of their menopause. Moreover, as women age, there are changes in body composition that include losses in bone mineral and body cell mass, and increases in total body fat, visceral fat, and extracellular fluid. It appears as if these body composition changes begin or accelerate during the menopausal years. The importance of weight gain and changes in body composition are their associations with an increased risk of developing some malignancies, cardiovascular disease, osteoporosis, and several other clinical conditions. This overview describes selected studies of menopause and aging-associated weight gain, changes in body composition, and alterations of energy expenditure in women. Gaps in the present understanding of these changes are highlighted, and an emphasis is placed on new research methodologies for investigating body composition and energy expenditure in vivo. A concluding section of the report summarizes areas in need of future investigation.     

Relation of race, age, and sex hormone differences to serum leptin concentrations in children and adolescents

We explored the effects of race, age, and sex hormones on the serum leptin concentrations in 203 white and 88 black children and adolescents (ages 9.3-20.5 years). A significant sex by race interaction on serum leptin levels (p = 0.0301) was observed with lower serum leptin concentrations, adjusted for subscapular thickness and age, in black boys than in white boys. Girls had serum leptin levels that were on average 2.15 times those of boys (p < 0.0001). There was an age by sex interaction (p < 0.0001) with serum leptin concentrations decreasing in boys but not in girls with age. A strongly inverse relationship of serum testosterone levels with serum leptin levels in boys (p = 0.0067) appeared to explain this effect of age. In conclusion, the serum leptin concentration is slightly lower in black boys. A higher testosterone level in boys appears to account for an age-related decline in serum leptin in boys and the overall lower levels in boys than in girls.     

Effects of glucocorticoids and of growth hormone on serum leptin concentrations in man

To evaluate cardiopulmonary involvement in schistosomiasis mansoni, 246 patients from an endemic area of Brazil were examined; 152 had been previously treated for schistosomiasis. Based on stool examination and/or abdominal ultrasonography, the patients were divided into those with schistosomiasis (69%) and those in whom the disease was not present (31%). M mode measurements were similar in the 2 groups. Pulmonary pressure was measured by Doppler echocardiography; 25% of the subjects had pulmonary hypertension. Those with pulmonary hypertension had a higher prevalence of schistosomiasis (80%) than those without (64%; P = 0.03). No case of cor pulmonale was diagnosed by electrocardiography or Doppler echocardiography. The prevalence of pulmonary hypertension correlated neither with periportal fibrosis nor with prior treatment for schistosomiasis.     

No evidence for a higher resting metabolic rate in noninstitutionalized Alzheimer's disease patients

OBJECTIVE: It has previously been suggested that Alzheimer's disease patients have higher resting energy requirements than healthy individuals, which may contribute to their unexplained weight loss. We examined whether resting metabolic rate, the largest component of daily energy expenditure, is elevated in Alzheimer's patients compared with healthy older controls. DESIGN: Cross-sectional. SETTING: General Clinical Research Center and Baltimore VA Medical Center. PATIENTS: Twenty-five noninstitutionalized demented patients (74 +/- 8 years; mean +/- SD) with a wide range of Mini-Mental Examination scores (1 to 20) and 73 healthy older individuals (69 +/- 7 years). MEASUREMENTS: Resting metabolic rate was measured by indirect calorimetry, fat-free mass and fat mass by dual energy X-ray absorptiometry, and daily energy intake by food diaries. RESULTS: No differences in fat-free mass and fat mass were noted between Alzheimer's disease patients and healthy older controls. Resting metabolic rate was similar in Alzheimer's disease patients (5446 +/- 962 kJ/day) and healthy older individuals (5647 +/- 887 kJ/day). These results persisted when resting metabolic rate was statistically adjusted for differences in body composition and age. CONCLUSION: These results provide no evidence for an elevation in resting energy requirements in noninstitutionalized demented patients.     

Annual changes in serum vitellogenin concentrations in viviparous eelpout, Zoarces elongatus

Vitellogenin of matrotrophic viviparous eelpout (Zoarces elongatus) was purified from estradiol-17 beta (E2) treated immature male sera by gel chromatography and anion exchange chromatography. Isolated vitellogenin has a molecular weight of 540 kDa estimated by gel chromatography. Serum levels of vitellogenin in females were measured during oocyte development and gestation by single radial immunodiffusion. Serum vitellogenin level was low (less than 0.2 mg/ml) during the early vitellogenic period, increased in the late vitellogenic period to a peak level (6.4 +/- 2.1 mg/ml) at the beginning of gestation. After that it rapidly decreased to a low level (0.1 +/- 0.1 mg/ml) during the early gestation period. Levels of vitellogenin remained low throughout the gestation period. Serum E2 levels in females showed increased from 1.3 to 3.0 ng/ml during the late vitellogenic period, and declined to 0.4 ng/ml during the early gestation period. Serum levels of E2 showed good correlation with serum vitellogenin levels, suggesting that the vitellogenin synthesis is controlled by E2 in this species. These results combined with the matrotrophic growth of embryo during gestation suggest that there is a shift in the synthesis of maternal nutritional products for embryos from the yolk to other nutrients.     

Effects of diet and diet-plus-exercise programs on resting metabolic rate: a meta-analysis

Studies examining the effects of diet (D) and diet-plus-exercise (DE) programs on resting metabolic rate (RMR) report equivocal results. The purpose of this study was to use meta-analysis to determine if exercise prevents the decrease in RMR observed with dieting. Results from the 22 studies included in this analysis revealed that the majority of studies used female subjects ages 31-45 years, who were fed a relatively low-fat, high-carbohydrate diet of less than 5,023 kJ.day-1. The predominant prescribed exercise was aerobic in nature, 31-60 min in duration, performed 4-5 days per week, and of moderate intensity (51-70% of VO2max). Contrary to what is reported in narrative reviews, RMR decreased significantly with both D and DE programs, and the drop with D was significantly greater than that with DE. In conclusion, the addition of exercise to dietary restriction appears to prevent some of the decrease in RMR observed in premenopausal women.     

Relaxin levels in amniotic fluid, extraembryonic coelomic fluid and maternal serum in early human pregnancy

Separately identified samples of amniotic fluid and extraembryonic coelomic fluid together with maternal serum were collected from 22 women between 8 and 11 weeks of pregnancy and analysed for relaxin by immunoassay. Relaxin levels in maternal serum (median 1085 pg/ml; range 390-1259 pg/ml) were substantially higher than those in extraembryonic coelomic fluid (median 57.5 pg/ml; range 17-145 pg/ml; P < 0.0001; Mann-Whitney U-test). In turn, the levels of relaxin in coelomic fluid were higher than those in amniotic fluid (median 10 pg/ml; range 10-37 pg/ml; P < 0.0001; Mann-Whitney U-test). A linear correlation was found between relaxin levels in maternal serum and coelomic fluid (r = 0.68; P = 0.001) but there was no relation between levels in the other fluid compartments.     

Dynamics of serum immunoglobulin concentrations in sheep during pregnancy and lactation

The relationship between endurance time and the mean force of contraction was investigated in intermittent and sustained static contractions over a long period of time (60 min). For intermittent static contractions the endurance limit of the mean force of contraction was found to be 14.0%, and for sustained static contractions it was 7.9% of the maximal force of contraction. Weak subjects appear to have a higher endurance limit of force than strong subjects.     

Activin A and inhibin B in extra-embryonic coelomic and amniotic fluids, and maternal serum in early pregnancy

Activin A and inhibin B levels were measured, using a two-site enzyme immunoassay, in extra-embryonic coelomic fluid, amniotic fluid and maternal serum samples retrieved from 23 healthy pregnant women, at 8 (n=8), 9 (n=8), and 10 (n=7) weeks of gestation. Dimeric activin A and inhibin B were measurable in all samples. Median (+/-SEM) activin A concentrations in coelomic fluid (0.98+/-0.34 ng/ml) were significantly higher than in maternal serum (0.68+/-0.05 ng/ml) and in amniotic fluid (0.09+/-0.04 ng/ml) (P<0.05). Maternal serum activin A levels were significantly higher than amniotic fluid concentrations. Median (+/-SEM) inhibin B concentrations in coelomic fluid (24.32+/-6.02 pg/ml) were significantly higher than in maternal serum (5.94+/-0.97 pg/ml) and in amniotic fluid (6.31+/-1.53 pg/ml) (P<0.05), while no significant difference between maternal serum levels and amniotic fluid concentrations was found. No significant difference in activin A and inhibin B levels in extra-coelomic fluid, amniotic fluid, and maternal serum throughout the 3 weeks of pregnancy was found. The present study showed that coelomic fluid is an important reservoir of activin A and inhibin B, supporting the hypothesis that the extra-embryonic coelom may have a secretory role during the first 11 weeks of gestation.     

Plasma leptin concentrations: gender differences and associations with metabolic risk factors for cardiovascular disease

The cloning of the obese gene and the characterization of its protein product, leptin, has permitted the study of a new hormone potentially involved in the regulation of adipose tissue mass. The present study examined the gender differences in fasting plasma leptin concentration and its relationship to body fatness, adipose tissue distribution and the metabolic profile in samples of 91 men (mean age +/- SD: 37.3 +/- 4.8 years) and 48 women (38.5 +/- 6.8 years). Plasma leptin concentrations were strongly associated with body fat mass measured by underwater weighing [men: r = 0.80, p < 0.0001; women: r = 0.85, p < 0.0001]. In both genders, plasma leptin levels were also strongly correlated with waist girth as well as cross-sectional areas of abdominal subcutaneous and visceral adipose tissue measured by computed tomography. Women had, on average, plasma leptin concentrations that were three times higher than men. Furthermore, this gender difference remained significant when comparing men and women matched for similar levels of body fat mass. The associations between plasma leptin and lipoprotein concentrations were dependent of adiposity. In both men and women, elevated fasting plasma leptin levels were associated with higher plasma insulin concentrations, but only in women was the association maintained after correction for fat mass. Thus, results of the present study show that women have higher plasma leptin levels compared to men, independent of the concomitant variation in total body fat mass. Furthermore, our results also suggest that, in women, the association between plasma leptin and insulin concentrations is independent of adiposity, a finding which provides further support to the observation that adipose tissue leptin secretion may be upregulated by insulin.