Sexual dimorphism in circulating leptin concentrations is not accounted for by differences in adipose tissue distribution

BACKGROUND: Circulating concentrations of leptin normalized to total adipose tissue mass are significantly greater in females than in males. Rates of leptin expression (per gram of adipose tissue) are significantly greater in subcutaneous (SAT) than visceral (VAT) adipose tissue and the relative amount of fat stored as SAT vs VAT is significantly greater in pre-menopausal females than in males. Gender-related differences in the relative amounts of SAT and VAT may account for the greater circulating leptin concentration relative to fat-mass in females than males. METHODS: We examined body composition and anatomic fat distribution by dual energy X-ray-absorptiometry (DEXA) and magnetic resonance imaging (MRI), and post-absorptive circulating concentrations of leptin and insulin in 58 subjects (26 females, 32 males). Stepwise multiple linear regression analyses, treating gender as a dichotomous variable, were performed to determine inter-relationships among leptin concentrations and insulin concentrations, VAT and SAT. RESULTS: Body composition by DEXA and MRI were highly correlated (r(2)=0.97, P<0.0001). There were significant gender effects on leptin/total fat mass (males, 0.17+/-0.01 ng/ml/kg; females, 0.49+/-0.05 ng/ml/kg; P<0.0001) and relative amounts of fat in SAT and VAT depots (ratio of SAT/VAT; males, 12.3+/-1.5; females, 32.9+/-3.2; P<0.0001). Circulating leptin concentration was significantly correlated with insulin concentration (P=0.001), SAT (P<0.0001) and gender (P=0.033). Circulating concentrations of insulin were significantly correlated with VAT, but not SAT, in males and with SAT, but not VAT, in females. CONCLUSIONS: The sexual dimorphism in the relationship between leptin and adipose tissue mass cannot be explained by differences in the relative amounts of VAT and SAT. Thus, the sexual dimorphism in plasma leptin concentration appears to reflect, at least in part, effects of circulating concentrations of gonadal steroids (especially androgens) and/or primary genetic differences that are independent of amounts of VAT or SAT.     

Relationship between serum adiponectin and leptin concentrations and body fat distribution

The aim of this study was to investigate the relationship between adiponectin and leptin and body fat distribution. One hundred and ninety-seven women participated in this study. Subjects were grouped based on their visceral adipose tissue area (VAT). Body fat distribution was determined by computed tomography. The numbers in the subcutaneous fat dominant group (SFDG) and visceral fat dominant group (VFDG) were 79 and 118, respectively. The VFDG showed lower adiponectin levels than the SFDG (8.9+/-0.4 microg/ml versus 11.4+/-0.7 microg/ml, P=0.006), but leptin levels did not differ significantly between groups (18.8+/-1.1 ng/ml versus 17.7+/-1.8 ng/ml, P=0.111). Adiponectin levels were inversely correlated with fasting insulin, HOMA-IR, triglyceride, SBP and DBP, subcutaneous adipose tissue area (SAT) and VAT, and waist-to-hip ratio (WHR). Leptin levels were positively correlated with fasting glucose and insulin, HOMA-IR, triglyceride, SBP and DBP, VAT and SAT, and WHR (all values of P<0.05). VAT and HDL-cholesterol were independent variables of adiponectin concentrations (R(2)=0.207, P<0.0001), and SAT, fasting insulin, and HOMA-IR were independent variables of leptin concentrations (R(2)=0.498, P<0.0001) In conclusion, adiponectin and leptin concentrations, although associated with metabolic parameters, were more strongly influenced by VAT in the case of adiponectin, and by SAT in the case of leptin.     

Effects of a 3-week integrated body weight reduction program on leptin levels and body composition in severe obese subjects

The effects of short-term (3 weeks) integrated body weight reduction (BWR) program (including energy-restricted diet, aerobic and strength exercise (5 days/week), nutritional education and psychological counseling) on plasma leptin levels and body composition were investigated in 54 morbidly obese patients (38 females/16 males; mean BMI +/- SE: 41.8 +/- 0.1 kg/m2, range 35-58 kg/m2; mean age: 29.8 +/- 1.0 yr, age range: 18-46 yr). The BWR program induced a significant (p < 0.001) weight loss (BMI reduction: -4.8%) and a significant modification in body composition, consisting in a fat mass (FM) decrease (-7.0 +/- 0.4%, p < 0.001) with a concomitant fat-free (FFM) mass increase (1.8 +/- 0.3%, p < 0.001). On average, plasma leptin levels decreased significantly both in males (from 19.4 +/- 2.6 ng/ml to 11.6 +/- 1.3 ng/ml, p < 0.001) and in females (from 41.1 +/- 3.6 ng/ml to 29.9 +/- 3.0 ng/ml, p < 0.001). Both before and after weight loss, leptin levels were positively correlated (p < 0.001) with BMI and percent fat mass (FM) values. Weight changes after the BWR program were negatively correlated with baseline leptin concentrations both in absolute terms and expressed per unit FM. In conclusion, a short-term diet plus aerobic/strength training effectively induces body composition changes and reduces plasma leptin levels. Body FM reduction appears to be not the unique determinant of leptin levels regulation and the degree of leptin over-expression may negatively affect weight loss in morbidly obese patients.     

Plasma leptin concentrations are related to body fat mass and gender but not to thyroid dysfunction

Leptin, a newly defined protein synthesized and secreted from fat cells in both animals and humans, has gained wide attention. Many studies have been conducted on its roles in the regulation of body fat storage, energy expenditure and body weight changes. Thyroid dysfunction is known to have influences on the above changes in humans and these changes may in turn lead to a variation in circulating leptin levels. In addition, a sex dimorphism of plasma leptin levels has been a constant finding in many studies. However, the relationship between body fat mass and gender to plasma leptin levels in patients with various thyroid dysfunction has been rarely discussed together. A total of 134 patients with various thyroid function status were included in this study (hyperthyroidism: n = 50, hypothyroidism: n = 24, and euthyroidism: n = 60). Plasma leptin concentrations were compared between different thyroid function groups, and compared with body fat mass and body mass index (kg/m2) to check if these two parameters affect the circulating leptin levels. There were no significant differences between plasma leptin concentrations in the different thyroid function groups (Mean +/- SD: hyperthyroidism: 8.5 +/- 5.4 ng/ml, range: 1.5-25.8; hypothyroidism: 8.4 +/- 4.7 ng/ml, range: 1.8-20.1, and euthyroidism: 7.3 +/- 4.5 ng/ml, range: 0.6-20.9). Rather, a significant gender difference was found, with female subjects having two-fold higher levels than males when all study subjects were encompassed (female: 8.8 +/- 4.9 ng/ml, range: 11.7-25.8 vs male: 4.1 +/- 2.1 ng/ml, range 0.6-8.1, p < 0.001) or when thyroid function status was analyzed separately (hyperthyroidism: female: 9.7 +/- 5.5 ng/ml vs male: 4.3 +/- 2.1 ng/ml, p < 0.001; hypothyroidism: female: 9.7 +/- 4.6 ng/ml vs male: 4.4 +/- 2.4 ng/ml, p = 0.015; and euthyroidism: female: 7.9 +/- 4.5 ng/ml vs male: 3.6 +/- 1.9 ng/ml, p = 0.013). Plasma leptin concentrations had strong correlation with body fat mass in both females (r = 0.47, p < 0.001) and males (r = 0.71, p < 0.001). Good correlation was also observed between plasma leptin concentrations and body mass index in females (r = 0.51, p < 0.001) and males (r = 0.78, p < 0.001). Plasma leptin concentrations were not different in thyroid dysfunction. A significant gender difference existed and a positive correlation between body fat mass and BMI to plasma leptin was observed.     

Serum leptin concentration in moderate and severe obesity: relationship with clinical, anthropometric and metabolic factors

OBJECTIVE: To study clinical, anthropometric and metabolic determinants of serum leptin concentrations in a series of patients with a wide range of obesity. SUBJECTS: 400 patients, 116 males and 284 females, aged 44+/-12.3 years with body mass index (BMI) ranging from 31 to 82 kg/m2 (mean 41.4+/-7.1). MEASUREMENTS: Energy intake by 7-day recall, resting energy expenditure (REE) by indirect calorimetry, body composition determined by bioelectrical impedance; C index, an anthropometric index of abdominal fat distribution, and waist-hip ratio (WHR), blood glucose serum leptin concentrations, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, uric acid, and insulin concentrations HOMA IRI (homeostastis model assessment of insulin resistance index). RESULTS: Leptin concentrations were higher in obese than in normal subjects and in females than in males without differences between diabetic and non-diabetic patients; leptin concentrations were not related to age and showed a strong negative association with energy intake only in the group of women with BMI less than 40. Leptin concentrations showed a direct correlation with BMI and body fat values (expressed either as percentage of total body mass or absolute fat mass) independent of age and sex. After adjustment for fat mass, leptin values higher than predicted were found in women whereas concentrations lower than predicted were found predominantly in men. Leptin showed an inverse correlation with WHR and C-index, the latter persisting also after correction for gender and fat mass. REE, but not REE/kg fat-free mass (FFM) was inversely related to leptin also after correction for sex and absolute fat mass. Leptin concentrations were directly associated with HOMA IRI, insulin and HDL cholesterol and inversely associated with triglycerides and uric acid. The relationship of leptin with HOMA IRI was still evident after adjusting for sex but was lost when absolute fat mass was added to the model; HDL cholesterol and triglycerides appeared to be variables independent of leptin concentrations even when both sex and fat mass were added to the model. CONCLUSIONS: In a large group of obese patients (half of whom had severe obesity, gender, BMI and fat mass accounted for the largest proportion of serum leptin concentrations variability. We found that in obese subjects there is an effect of fat distribution on leptin concentrations and that, after excluding variability due to absolute fat mass, patients with a greater amount of abdominal fat have relatively low leptin concentrations which in turn relates to a metabolic profile compatible with an increased cardiovascular risk. Women with milder obesity may retain some degree of control of food intake by leptin.     

Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor,free leptin index,adiponectin, and resistin concentrations in healthy humans

The adipocyte-derived hormones leptin [which circulates in a free form and bound to a soluble leptin receptor (sOB-R)], adiponectin, and resistin play a key role in regulating energy homeostasis and metabolism. We assessed the association between body composition, total energy, and macronutrient intake and serum leptin, sOB-R, free leptin index, adiponectin, and resistin concentrations in 61 female and 53 male consecutively enrolled healthy Greek students. In this cross-sectional study, total energy and macronutrient intake were determined using 3-d food records. Body composition was assessed by bioelectrical impedance analysis; fasting blood samples were taken for the measurement of total leptin, sOB-R, adiponectin, and resistin; and the ratio leptin/sOB-R was used as an index of free leptin. Serum sOB-R concentrations were lower in the female subjects compared with the males (27.24 +/- 29.06 vs. 50.14 +/- 39.74 ng/ml, P < 0.001), whereas leptin, adiponectin, and resistin concentrations were significantly higher in females (leptin: 9.93 +/- 6.01 vs. 3.27 +/- 2.54 ng/ml, P < 0.001; adiponectin: 11.40 +/- 6.73 micro g/ml vs. 4.90 +/- 2.79 micro g/ml; P < 0.001; resistin: 16.86 +/- 5.39 ng/ml in females vs. 14.00 +/- 7.16 ng/ml in males, P < 0.02). Simple regression analysis showed that, in both genders, leptin, free leptin index, adiponectin, and resistin correlated positively with body fat mass and negatively with waist to hip ratio. sOB-R correlated negatively with body fat mass and positively with waist to hip ratio. Multiple regression analysis models controlling for gender, body fat, and total energy intake demonstrated that sOB-R is positively associated with energy intake from carbohydrates and negatively with energy intake from dietary fat, whereas free leptin index is negatively associated with energy intake from carbohydrates and positively with energy intake from dietary fat. No statistically significant correlations were observed between serum adiponectin or resistin concentrations and total energy or macronutrient intake. Thus, total energy intake and macronutrient composition of the diet are associated with sOB-R and free leptin index but do not play a role of comparable significance in predicting adiponectin and resistin concentrations in healthy young subjects.     

Serum lipid and leptin concentrations in hypopituitary patients with growth hormone deficiency

OBJECTIVE: To investigate the effects of growth hormone (GH) deficiency on serum lipid and leptin concentrations in hypopituitary patients taking conventional replacement therapy and to determine the relations between leptin and gender and anthropometric and metabolic variables. SUBJECTS: Twenty-one GH deficient adult hypopituitary patients (15 women, six men) and 21 (14 women, seven men) age, sex and body mass index (BMI) matched healthy controls. MEASUREMENTS: After an overnight fast, anthropometric parameters were measured and body composition was determined by a bioelectrical impedance analyser. Venous blood samples were obtained for the measurements of glucose, total cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride, intact insulin, insulin-like growth factor 1 (IGF-1) and leptin concentrations. Serum leptin and hormones were analysed by radioimmunoassay. RESULTS: Hypopituitary patients with GH deficiency showed significantly higher triglyceride, total and low density lipoprotein (LDL) cholesterol and lower HDL cholesterol concentrations on conventional replacement therapy. The unfavourable lipid profile was particularly evident in women. Significantly higher leptin concentrations were found in patients compared with healthy controls with similar body fat content (23. 5+/-11.8 ng/ml vs 11.7+/-6.9 ng/ml, P=0.01). This difference remained significant even when leptin values were expressed in relation to fat mass percentage (0.79+/-0.40 vs. 0.42+/-0.17 ng/ml%, P<0.05) and fat mass kg (1.32+/-0.81 vs 0.66+/-0.30 ng/ml kg, P<0. 05). Significant positive correlations were observed between leptin concentrations and body fat percentage and age in the control group. In patients the sole significant relation between leptin and study parameters was the positive correlation observed between leptin and total cholesterol concentrations. Serum leptin concentrations were significantly higher in women than men in the control group, but not in the patients. No significant gender difference was observed when leptin concentrations were expressed in relation to fat mass (percentage and kg). CONCLUSION: Growth hormone deficient hypopituitary patients (particularly women) on conventional replacement therapy have a more atherogenic lipid profile. Leptin concentrations are increased in GH deficient adults even after adjustment for percentage body fat and body fat mass (kg). Although the nature of our data does not allow us to draw any conclusions on the mechanism(s) of increased leptin concentrations in GH deficiency, decreased central sensitivity to leptin and increased leptin production from per unit fat mass, or alterations in leptin clearance, might be operative.     

Diurnal rhythm of serum leptin in patients with solid tumors

Leptin is a protein produced by fat tissue. It has many regulatory effects in the area of energetic metabolism, immunity and haematopoiesis. Its role in tumour diseases especially in states with cachexia is studied. Its physiological diurnal rhythm is very well known. There is lack of information about diurnal rhythm of leptin in tumour diseases except some endocrine tumours. In this study 10 patients with breast and colorectal cancer without marks of kachexia and mostly without pre-existing chemotherapy were examined. The diurnal rhythm of leptin was preserved in cancer patients (morning minimum 10.5 +/- 4.2 ng/ml and nocturnal maximum 17.9 +/- 10.1 ng/ml). The difference between males and females (p < 0.01) and correlation of concentrations of leptin with BMI (r = 0.61, p < 0.001) were preserved too. Basal concentrations of leptin were not different from values of healthy blood donors (10.2 +/- 4.3 ng/ml). Maybe preservation of diurnal rhythm of leptin can be important in planning of cytostatic and immunomodulatory therapy in future.     

Serum leptin and lipids in patients with thyroid dysfunction.

This work was undertaken to examine the relationship between thyroid hormone and serum leptin concentration. This study included 368 Japanese female subjects (27 were affected with pretreatment hyperthyroidism, 68 with hyperthyroidism during treatment, 19 with pretreatment hypothyroidism, 57 with hypothyroidism during treatment and 197 euthyroid control subjects) and 60 control male subjects. In the control group, serum leptin levels in males were lower than those recorded in females (mean +/- SD; 4.6 +/- 4.1 vs 9.5 +/- 6.4 ng/ml, p < 0.001). The leptin values correlated well with body mass index (BMI) and body fat mass (BFM) in both control male and female subjects (p < 0.001 for each). The serum leptin levels in pretreatment female patients with hyperthyroidism were significantly lower than those in the pretreatment patients with primary hypothyroidism and control female subjects (6.4 +/- 3.0 vs 9.7 +/- 6.3, 9.5 +/- 6.4 ng/ml; p < 0.05, 0.02, respectively), but after adjusting for BMI and BFM, the difference was mainly due to the significantly different BMI and BFM. Furthermore, serum leptin did not change significantly during the treatment in hyper and hypothyroidism. There was no correlation between serum leptin and thyroid hormones or lipids levels in female patients with thyroid disorders. Adiposity and gender were the major determinants of leptin concentration, but thyroid hormones did not appear to play any relevant role in leptin synthesis and secretion in human.     

Associations of leptin with body fat distribution and metabolic parameters in non-insulin-dependent diabetic patients: no effect of apolipoprotein E polymorphism

Leptin levels have been shown previously to be associated with anthropometric parameters such as the body mass index (BMI), total body fat, and subcutaneous fat. Since apolipoprotein E (apoE) polymorphism is known to be a genetic marker affecting the relationship between certain anthropometric and metabolic parameters, we evaluated whether the leptin level and/or associations between the leptin level and body composition in non-insulin-dependent diabetic patients could be determined by apoE polymorphism. In 171 type 2 diabetic patients (105 male and 66 female), body composition (BMI, waist to hip ratio [WHR], fat mass, and visceral fat) was measured and fasting blood samples were obtained to determine the apoE genotype, leptin, glucose, and insulin levels, and the lipid profile. The mean leptin level for the whole group was 11.7 +/- 9.3 ng/mL, with a significant difference (P < .001) between men (7.1 +/- 4.9 ng/mL) and women (19.0 +/- 10.1 ng/mL). No difference was found for leptin levels or anthropometric variables between the 3 different apoE genotypes (E3/E3 homozygotes, E2 carriers, and E4 carriers). Only low-density lipoprotein (LDL) cholesterol was significantly different between the 3 apoE subgroups. The correlations of leptin with anthropometric variables, especially visceral fat, tended to be different between the 3 apoE groups, but this was not independent and no effect was found after controlling for the other parameters in the model. A multiple regression model containing gender, subcutaneous fat, fasting glucose, triglycerides, and high-density lipoprotein (HDL) cholesterol explained 81% of the variance in leptin levels. We conclude that apoE polymorphism has no effect on the leptin level or its associations with other anthropometric and metabolic parameters.     

The relation between plasma leptin concentration and body fat mass in patients with rheumatoid arthritis

The prospective, cross-sectional study was undertaken to evaluate the relation between the fat mass and serum leptin level in patients with rheumatoid arthritis (RA). Low body mass and anorexia are commonly found in patients with RA. Inflammatory cytokines may significantly influence the secretion of anorectic hormone--leptin--that was confirmed in both experimental and clinical studies. Fifty-two non-diabetic and non-obese patients (38 females, 14 males) were studied. Mean age was 56 +/- 11 years and mean body mass index (BMI) 24.6 +/- 4.1 kg/m2. The disease activity score (DAS) was 3.9 +/- 1.4; range 1.4-7.4, and disease duration 8.1 +/- 6.7 years. Serum leptin was measured by ELISA and body composition by double X-ray densitometry. Mean serum leptin concentration was 2.8 +/- 1.4 ng/ml in patients with RA was lower than in the control group (4.2 +/- 2.0). In a simple regression analysis leptin did not correlate with BMI (R Spearman = 0.01), C-reactive protein (R = 0.08), total fat mass (R = 0.08), trunk fat (R = 0.05), limbs fat (R = 0.09) and DAS (R = -0.17). This relation was also not influenced by gender or type of immunosuppressive therapy. In a multiple regression model none of the independent variables explained the significant portion of variance of serum leptin. It is concluded that the physiologic relation of serum leptin to body fat stores is not present in patients with RA.     

Serum leptin levels in female patients with protein-calorie malnutrition and its relation to biochemical indicators of nutritional status

Leptin is a protein hormone produced by adipocytes. Its serum concentrations in the most of cases positively correlate with total body fat content. Serum leptin levels are increased in obese in comparison with lean subjects. Leptin levels in females are two or three times higher than in body mass index and age-matched males. The aim of our study was to investigate the serum leptin concentrations in females with protein-caloric malnutrition of various aetiology, the relationship between leptin levels and biochemical nutritional parameters and to compare the values with those of age-matched control group. Totally 12 patients with malnutrition of various aetiology and 14 control age-matched healthy subjects were included into the study. It was found that serum leptin levels were significantly decreased in malnutrition group in comparison with control group (3.09 +/- 1.33 ng.ml-1 vs 9.42 +/- 2.76 ng.,l-1, p < 0.05). A significant decrease in body mass index, serum total protein, albumin, prealbumin, cholesterol and triglycerides concentration was also found in malnutrition in comparison with control group. While a strong positive correlation between leptin concentrations and body mass index was found in control group (r = 0.72, p < 0.05), no statistically significant relation between leptin and body mass index was observed in malnutrition group. Furthermore, no significant relationship was found between serum leptin levels and serum total protein, albumin, prealbumin, cholesterol and triglycerides neither in control or in malnutrition group. We conclude that serum leptin levels in patients with malnutrition are significantly decreased in comparison with age-matched healthy control subjects. The loss of positive correlation between leptin and body mass index in malnutrition group is explainable by the changes of body composition in patient with malnutrition. The body mass index value in these patients reflects the total body fat content less precisely than in healthy controls.     

Effect of small doses of dexamethasone on plasma leptin levels in normal and obese subjects: a dose-response study

To further elucidate the role of glucocorticoids in the regulation of leptin secretion, we studied the effects of overnight small doses of dexamethasone on plasma leptin levels in normal weight controls and in obese patients and correlated the results with indexes of insulin sensitivity and body fat distribution. In 114 subjects (81 obese patients, 49 women and 32 men, BMI 37.4 +/- 0.77 kg/m2 and 33 normal-weight subjects, 17 women and 16 men, BMI 22.1 +/- 0.41 kg/m2) plasma F and leptin levels were measured at 08:00 h basally and after the administration of different doses of dexamethasone (a fixed dose of 1-mg and 0.0035, 0.007, 0.015-mg/kg bw, given po at 23:00 h the night before). Tests were performed one week apart with bw remaining stable over the study period. Basal leptin levels were significantly higher in obese than in normal subjects (31.9 +/- 2.41 vs 7.7 +/- 0.93 ng/ml, p<0.0001). In obese patients, leptin levels increased significantly by 1-mg (from 31.9 +/- 2.41 to 35.0 +/- 2.59 ng/ml, p<0.005) and the 0.015-mg/kg bw dose (from 31.5 +/- 2.34 to 33.7 +/- 2.44 ng/ml, p<0.05), while they were unaffected by each dose of dexamethasone in normal subjects. However, after splitting subjects by gender, mean leptin levels rose from 39.3 +/- 2.97 to 43.3 +/- 3.12 ng/ml after the 1-mg dose, p<0.005, from 39.1 +/- 2.87 to 43.6 +/- 2.91 ng/ml after the 0.015-mg/kg bw dose, p<0.005, from 39.3 +/- 2.90 to 42.2 +/- 2.90 ng/ml after the 0.007-mg/kg bw dose, p<0.05 and from 38.8 +/- 2.66 to 41.1 +/- 2.87 ng/ml after the 0.0035-mg/kg bw dose, p=0.055, only in obese women. Conversely, no leptin changes were seen in the other groups and no differences were observed in the leptin response between groups. After the 1-mg dose, in the whole group, the absolute leptin variation was weakly but significantly related to BMI values (r=0.231, p<0.02) while in all sessions the percent leptin changes over baseline were not significantly correlated with age, BMI, waist, WHR, insulin, HOMA index, a marker of insulin sensitivity, plasma dexamethasone concentrations and to the percent cortisol variation following dexamethasone. In conclusion, in obese women but not in obese men and in normal weight subjects, small overnight increases in plasma glucocorticoid concentrations induced gender-related plasma leptin elevations that were unrelated to body fat distribution and insulin sensitivity. A greater sensitivity of female adipose tissue to glucocorticoids probably underlies this sexually dimorphic pattern of leptin response. These findings provide an additional piece of information on the regulation of leptin secretion exerted by glucocorticoids.     

Reduction of leptin precedes fat loss from running exercise in insulin-resistant rats.

Serum concentrations of leptin, a hormone secreted into the circulation by adipocytes, correlate with body mass index. Circulating of leptin is thought to signal the brain in patients with hyperinsulinemia, a condition reported to be preventable and testable by exercise training. In the present experiments, sucrose-fed rats had reduced concentrations of leptin in portal venous blood after 4 weeks of nonforced wheel-running exercise (1.1 +/- 0.1 vs. 6.2 +/- 1.8 ng/mL, in nonexercised sucrose-fed rats, P < 0.05). Mesenteric and subcutaneous fat stores were similar between groups. After 12 weeks of exercise, portal vein levels of leptin concentrations (5.2 +/- 2.1 vs. 9.9 +/- 0.8 ng/mL, P < 0.05) and mesenteric and subcutaneous fat all were reduced in the exercise group. These results suggest that short-term running exercise reduces circulating leptin before any reduction of adipose mass, and this reduction in the concentration of leptin available to its receptors has beneficial effects on the metabolism of fat and carbohydrates.     

Effects of anabolic-androgenic steroid use or gonadal testosterone suppression on serum leptin concentration in men.

OBJECTIVE: Serum leptin concentration shows a sexual dimorphism that is not accounted for by gender differences in adiposity. A strong inverse association exists between serum leptin and testosterone concentrations in men, pointing to a likely influence of gonadal sex steroids on serum leptin concentration. The aim of this study was to investigate whether manipulation of sex steroid hormones in men would alter serum leptin concentration independently of changes in fat mass. DESIGN AND METHODS: The effects of sex steroid suppression on serum leptin concentration were investigated in nine healthy men in whom testosterone had been reversibly suppressed for 5 weeks after treatment with intramuscular triptorelin. The effects of sex steroid supplementation were investigated in nine male bodybuilders who self-administered anabolic--androgenic steroids (AAS) for a mean period of 6.5 weeks. A control group received no hormonal treatment. RESULTS: Testosterone concentration was significantly reduced by triptorelin administration (7.32+/- 1.92ng/ml at baseline compared with 1.15+/-0.57ng/ml at 5 weeks, P=0.002). High-dose AAS use was confirmed by urine analysis. Body fat percentage was unaffected by the AAS or triptorelin intervention (P>0.19). Leptin concentration was significantly reduced after one cycle of AAS use (2.40+/-0. 98ng/ml off cycle compared with 1.63+/-0.37ng/ml on cycle, P=0.012), and was significantly increased by triptorelin administration (2. 96+/-1.50ng/ml at baseline compared with 6.63+/-4.67ng/ml at five weeks, P=0.004). No significant change occurred in the control group. CONCLUSION: Androgenic sex hormone supplementation decreases serum leptin concentration, whereas suppression increases serum leptin concentration, independently of changes in body fat mass in healthy men. The sexual dimorphism evident in serum leptin concentration is likely to be due to a suppressive effect of testosterone on serum leptin concentration in males.     

Serum leptin concentration in peritoneal dialysis patients: determinants, longitudinal evolution and circadian rhythm

The serum concentration of leptin, an hormone secreted by adipocytes, is increased in obese and chronic renal failure patients. To determine the influence of peritoneal dialysis (PD) therapy on serum leptin levels, we analyzed its concentration in 23 patients on PD for an average of 26.8 +/- 7.1 months and compared it to that of 18 patients with chronic renal failure (creatinine clearance: 49.1 +/- 8.8 ml/min) and of 35 healthy control subjects. Leptin level was also reevaluated in 11 PD patients 9.3 +/- 1 months after the initial analysis. Finally, circadian leptin production was determined in 4 patients on automated PD (APD). Serum leptin was significantly higher in PD (31.9 +/- 7.8 ng/ml) than in chronic renal failure patients (15.2 +/- 5.9 ng/ml) and in healthy control subjects (9.6 +/- 1.1 ng/ml). Serum leptin level was significantly correlated with BMI in all three groups (except in PD males) and with the percentage of fat mass in both male and female PD patients. It did not correlate in PD patients with serum albumin concentration, free fat mass, residual diuresis, time on PD and characteristics of peritoneal permeability. At the second determination, serum leptin level had significantly increased in the PD patients although their respective BMI and serum creatinine concentration had remained virtually unchanged. Finally, in APD patients, the highest leptin level was observed at 08.00 a.m. These results demonstrate that serum leptin level is increased in PD patients and that it progressively rises under PD therapy. The circadian leptin production is delayed in APD patients probably suggesting a negative effect of the nocturnal glucose load on the regulation of its secretion.     

Assessment of abdominal fat distribution in obese patients: anthropometry versus computerized tomography.

The accuracy of waist to hip girth ratio (WHR) in assessing visceral/subcutaneous abdominal fat distribution has not yet been clearly established in the obese population. The purpose of the present study was to evaluate the relationship between WHR and visceral/subcutaneous fat distribution, both assessed by computerized tomography (CT), in a group of 28 obese patients (15 male, 13 female). Furthermore, 33 normal weight or slightly overweight subjects (23 male, 10 female) were studied as a control group. Obese subjects of both sexes were found to have higher values of WHR than non-obese; conversely visceral:subcutaneous fat area ratio (VSR) values did not differ significantly. Significant correlation between WHR and BMI was present both in males (r = 0.41, P < 0.01) and in females (r = 0.54, P < 0.01). In normal weight males significant correlations between WHR and visceral fat area or VSR were found. In obese males these correlations were much weaker. In normal weight females a significant correlation was found between waist circumference and visceral fat area, whereas in obese females no positive correlations were found between anthropometric measurements and CT indices of visceral fat distribution. In conclusion, WHR cannot be considered as a reliable index of visceral/subcutaneous fat distribution in obese patients, particularly if they are females.     

Relationship between plasma renin profile and leptinaemia in patients with essential hypertension

Both leptin and the renin-angiotensin system (RAS) can influence the activity of the sympathetic nervous system, water and electrolyte metabolism as well as vascular remodelling, which are all involved in the regulation of arterial blood pressure. Thus leptin and the RAS may act together in the pathogenesis of essential hypertension. The present study aimed to answer the following question: does an interrelationship exist between leptinaemia and the plasma renin activity (PRA) profile in normotensive and hypertensive subjects? Forty-three patients with essential hypertension (EHP) (23 females, 20 males, mean age 39.0 +/- 1.8 years, mean body mass index (BMI) 26. 8 +/- 0.6 kg/m2, mean arterial pressure (MAP) 123 +/- 2 mm Hg) and 32 healthy subjects (NTS) (18 females, 14 males, mean age 38.6 +/- 2. 2 years, mean BMI 25.4 +/- 0.5 kg/m2, MAP 95 +/- 1 mm Hg) were examined. Plasma leptin levels were estimated once after the administration of a diet containing 100-120 mmol Na/day and after overnight 8-h recumbency. PRA was estimated twice: first after the administration of a diet containing 100-120 mmol Na day and overnight 8-h recumbency (PRA I), and a second time after 3 days of sodium restriction (20 mmol Na/day), and 3 h of upright position (PRA II). Antihypertensive drugs were withdrawn 7 days before the study. In EHP plasma leptin concentration was insignificantly higher than in NTS (14.0 +/- 2.0 vs10.8 +/- 1.5 ng/ml respectively). Only females with hypertension showed a significant positive correlation between plasma leptin concentrations (expressed as the logarithmic values) and PRA I. Using the multiple regression analysis, in all studied subjects (EHP and NTS together), logarithm (log) of plasma leptin concentrations was significantly related to gender, BMI and MAP. Multiple regression analysis performed separately for EHP or NTS revealed a significant relation of log plasma leptin concentrations with gender and BMI. A significant correlation was found between log leptinaemia values and BMI, mean and systolic blood pressure respectively if the whole group of subjects (EHP+NTS) or EHP and NTS separately were analysed. Especially in hypertensive women a highly significant correlation was found between log plasma leptin concentrations and MAP. We conclude that a significant relationship between leptinaemia and PRA does exist in females with EH and that participation of both PRA and leptin in the pathogenesis of EH in females seems to be likely.     

Relation of serum leptin levels and regulation of resting energy expenditure

Leptin is a protein hormone produced by adipocytes. Its serum concentrations in the most of cases positively correlate with total body fat content and body mass index (BMI). Leptin plays a role in the food intake regulation. It also increases resting energy expenditure in hypoleptinaemic ob/ob mice. Its relationship to resting energy expenditure in human is less clear. The aim of our study was to follow the serum leptin levels in healthy females (n = 12) and males (n = 14) and their relationship to resting energy expenditure, body fat content, other antropometric and nutritional biochemical parameters. It was found that serum leptin levels were significantly higher in females comparing to males (6.8 +/- 3 ng.ml-1 vs. 2.6 +/- 1 ng.ml-1, p < 0.05). The serum leptin levels correlated positively with body fat content and body mass index in both groups. In females the positive correlation between body weight and serum leptin levels was found. No statistically significant relationship between serum leptin levels and resting energy expenditure, serum total protein, albumin or prealbumin concentration was found in any of studied groups. The results of our study do not testify to direct relationship between serum leptin levels and resting energy expenditure in young healthy individuals.     

Leptin levels in relation to body composition and insulin concentration in patients with endogenous Cushing's syndrome compared to controls matched for body mass index

Cushing's syndrome (CS) is associated with weight gain and visceral obesity. We examined the relationship between regional fat distribution and serum levels of leptin, cortisol and insulin. Twenty-three consecutive patients with recently diagnosed CS (18 with pituitary adenoma, 5 with adrenal tumor), where compared to obese controls, matched for age, sex and Body Mass Index (BMI). Serum insulin, leptin, cortisol, C-peptide and body composition determined by DEXA were measured. Serum leptin levels were significantly increased in patients with CS (36.9+/-3.8 vs 18.9+/-2.4 ng/ml, p<0.001; women: 40.1+/-4.6 vs 21.7+/-2.9 ng/ml, p<0.01; men: 27.9+/-5.7 vs 10.9+/-2.3 ng/ml; p<0.05), the same were fasting insulin levels (178+/-30 vs 81+/-10 pmol/l; p<0.01) and C-peptide (1.51+/-0.12 vs 0.77+/-0.07 nmol/l; p<0.001). In a subgroup of 12 patients, truncal fat mass was significantly elevated when compared to obese controls (19.2 kg vs 14.7 kg, p<0.01, and 42% vs 36% in percentage of truncal body tissue, p<0.05), whereas total fat mass was insignificantly increased. Serum leptin correlated positively to total body fat (%) as in patients with CS (r=0.94, p<0.001) as in controls (r=0.68, p<0.01). The correlation to truncal body fat (%) was also significant in both groups (CS: r=0.84, p<0.001; controls: r=0.63, p<0.01). Multiple regression showed that percent total body fat was the predictor of leptin concentrations among patients with CS (r2=0.88, p<0.001) whereas insulin did not contribute significantly to the variance in leptin concentrations. In controls, both leptin and insulin (r2=0.65, p<0.001) contributed significantly to the variations in leptin levels. Controlled for the differences in total body fat, patients with endogenous CS have significantly increased serum leptin levels, compared to BMI-matched obese controls. This suggests that hyperleptinemia in CS not primarily reflects changes in body composition, but is the result of different hormonal influences on adipose tissue.