Prolactin release is enhanced in proportion to excess visceral fat in obese women

Prolactin (PRL) promotes (visceral) fat accrual in a variety of animal models. The release of PRL by the pituitary is tonically inhibited by dopamine through activation of the dopamine D2 receptor (D2R) of lactotroph cells, and obese humans appear to have reduced D2R-binding sites in their brain. Therefore, we hypothesized that spontaneous PRL release is enhanced in obese humans. To evaluate this hypothesis, we measured 24-h plasma PRL concentrations at 10-min intervals in 11 obese premenopausal women [body mass index (BMI), 33.3 +/- 0.7 kg/m(2)] and 10 lean premenopausal women of similar age (BMI, 21.2 +/- 0.6 kg/m(2)). Total body fat was determined using dual energy x-ray absorptiometry, and sc and visceral fat area was measured by magnetic resonance imaging in 10 obese subjects. PRL secretion rate was estimated by deconvolution analysis. All subjects were studied in the early follicular stage of their menstrual cycle. PRL secretion was significantly enhanced in obese women (total daily release, 137 +/- 8; lean controls, 92 +/- 8 microg/liter.24 h; P = 0.001) in proportion to their BMI (r(2) = 0.55; P < 0.001). Interestingly, PRL release was particularly associated with the size of the visceral fat mass (total PRL secretion vs. visceral fat area, r(2) = 0.64; P = 0.006). These data show that spontaneous PRL release is considerably enhanced in obese women in proportion to the size of their visceral fat mass. Because PRL is inhibited by D2R activation we speculate that elevated PRL secretion may be due to reduced D2R availability in the brain.     

High plasma leptin is not associated with higher bone mineral density in insulin-resistant premenopausal obese women

Obesity's protective effect on bone density may be mediated through increased muscle mass, fat mass, increased estrogen, and possibly insulin and leptin levels. To determine the impact of leptin and insulin on bone metabolism, we studied 48 obese normally cycling premenopausal women (age, 31 +/- 10 yr; body mass index, 35.7 +/- 5 kg/m2): 28 insulin resistant (IR) and 20 insulin sensitive (IS) by McAuley index. Anthropometric, body composition, and bone mineral density (BMD) measurements were made, and serum leptin, insulin, free testosterone, IGF-I, bone remodeling markers, and calciotropic hormones were measured. Anthropometric, lifestyle, and biochemical markers were similar in the two groups. Despite higher circulating insulin and leptin levels, IR subjects had similar mean values of serum osteocalcin but higher C-telopeptide (P = 0.052). They had similar BMD at all skeletal sites compared with IS subjects. In the IR group, fat mass but not lean mass, serum leptin, insulin, testosterone, and IGF-I levels correlated positively with hip and/or total-body bone density with R varying between 0.38 and 0.65; no correlations were observed at the spine. Conversely, in the IS group, lean mass, but not fat mass, and only IGF-I correlated with hip BMD/total-body bone mineral content. In conclusion, there is a dichotomy in the impact of body composition parameters and insulin and leptin levels on bone parameters in obese individuals. The interaction between the fat-related endocrine system and bone seems to be complex and may be modulated by local resistance to the putative protective effect of insulin and leptin on bone.     

Cortisol secretion in relation to body fat distribution in obese premenopausal women.

Urinary cortisol output and serum cortisol concentrations were measured in the steady state, under "field" conditions, and during standardized inhibitory and stimulatory tests in premenopausal, obese women, and were analyzed in relation to adipose tissue distribution. Urinary cortisol output was increased under field conditions in women with an elevated waist to hip circumference ratio (WHR) and, in particular, in women with a large abdominal sagittal diameter, indicating visceral fat accumulation. However, dexamethasone inhibition of cortisol secretion was normal. Stimulation with corticotropin analogue and with physical (cold-pressor test) or mental (color-word or mathematic) stress tests also showed elevated responses of serum cortisol, but not of prolactin or growth hormone concentrations. It is suggested that women with visceral fat accumulation have elevated cortisol secretion due to an increased sensitivity along the hypothalamic-pituitary-adrenal axis, and that this may be causing their abnormal fat depot distribution.     

Altered neuroregulation of GH secretion in viscerally obese premenopausal women.

We used deconvolution analysis of 24-h plasma GH concentration profiles (10- min sampling intervals) to appraise GH secretion rates and elimination kinetics in obese (body mass index, approximately 34 kg/m2) premenopausal women with large visceral fat area (LVFA; n = 8) vs. small visceral fat area (SVFA; n = 8) as determined by magnetic resonance imaging. The subjects were matched for body mass index, body fat percentage, and age. The impact of the loss of 50% of prestudy weight excess induced by caloric restriction was assessed as well. The results were compared with those obtained in normal weight control women (n = 8). LVFA subjects manifested markedly (4-fold) reduced mean plasma GH levels, which was brought about by jointly diminished basal and pulsatile GH secretion. Moreover, visceral obesity was associated with loss of regularity of GH release, as established by the approximate entropy statistic. In contrast, SVFA subjects produced normal daily amounts of GH and exhibited mean 24-h plasma GH concentrations that were similar to those in normal weight controls. GH half-life and distribution volume were not different among the study groups. Importantly, weight loss did not affect the daily GH secretion rate in LVFA women, so that their mean plasma GH concentration remained considerably reduced (approximately 50%) compared with controls (despite the loss of approximately 40% of visceral fat). Normal GH kinetics in SVFA women were not significantly influenced by weight reduction. Thus, GH neuroregulation appears to be particularly altered in obese women with a tendency to store fat in their visceral adipose depot. Because weight loss did not reverse GH secretion rate in viscerally obese women, we speculate that relative hyposomatotropism is a primary feature of these women, which could be involved in their tendency to preferentially store excess fat in visceral adipose tissue.     

Hyperenterostatinemia in premenopausal obese women

Enterostatins [Val-Pro-Asp-Pro-Arg (VPDPR), Val-Pro-Gly-Pro-Arg (VPGPR), and Ala-Pro-Gly-Pro-Arg (APGPR)] are pentapeptides derived from the NH2-terminus of procolipase after tryptic cleavage and belong to the family of gut-brain peptides. Although enterostatin-like immunoreactivities exist in blood, brain, and gut, and exogenous enterostatins decrease fat appetite and insulin secretion in rats, the roles of these peptides in human obesity remain to be examined. To determine whether VPDPR and APGPR secretion is altered in obesity, serum VPDPR and APGPR levels were measured in 38 overnight-fasted subjects (body mass index, 17.9-54.7 kg/m2) before and after a meal. The mean fasting VPDPR in the serum of lean subjects was significantly lower than that in obese subjects [lean = 603 +/- 86 nmol/L (n = 17); obese, 1516 +/- 227 nmol/L (n = 21); P = 0.0023]. In addition, the rise in serum APGPR after a meal (postmeal/fasting ratio) was significantly higher in lean than in obese subjects [lean, 1.71 +/- 0.24 (n = 17); obese, 1.05 +/- 0.14 (n = 21); P = 0.0332]. The results of these studies show hyperenterostatinemia in obesity and a diminution in enterostatin secretion after satiety.     

Low dehydroepiandrosterone circulating levels in premenopausal obese women with very high body mass index.

Dehydroepiandrosterone (DHEA) has an anti-obesity effect in rodents and reduces body fat in normal men. Therefore, the plasma levels of DHEA were evaluated in nine premenopausal healthy women and in 13 menstrually active nondiabetic obese women, including patients (n = 6) with body mass index (BMI) over 40. In the obese group, a significant inverse correlation between DHEA levels and BMI was found. These results suggest that patients with severe obesity are unable to increase the DHEA adrenal production rate in order to parallel the increase in the hormone metabolic clearance rate (due to enlargement of body fat mass per se). The deficiency of this mechanism might itself contribute to the progressive fat accumulation in severe obesity.     

Systemic low-grade inflammation is related to both circulating and adipose tissue TNFalpha, leptin and IL-6 levels in obese women

OBJECTIVE: We assessed the relationships between four circulating acute phase proteins and the circulating and adipose tissue levels of three adipocytokines. SUBJECTS: In all, 15 nondiabetic obese women with a body mass index (BMI) above 32 kg/m(2) were investigated. METHOD: Circulating concentrations of C-reactive protein (CRP), alpha 1 acid glycoprotein (AAG), fibrinogen, alpha 1 antitrypsin and both circulating and adipose tissue levels of interleukin (IL)-6, tumor necrosis factor (TNF)alpha and leptin were measured by either nephelometry or enzyme-linked immunosorbent assay. RESULTS: We found a strong positive correlation between both circulating and adipose tissue levels of IL-6, TNFalpha and leptin and serum CRP levels. All these adipose tissue adipocytokines were also positively correlated with serum AAG levels. These correlations disappeared when adjusted for fat mass, suggesting that the relationship observed was dependent on fat amount. CONCLUSION: Our results indicate a strong relationship between adipocytokines and inflammatory markers, and suggest that cytokines secreted by adipose tissue in obese subjects could play a role in increased inflammatory proteins secretion by the liver.     

Short-term treatment with bromocriptine improves impaired circadian growth hormone secretion in obese premenopausal women

Context: A profound reduction of spontaneous as well as stimulated GH secretion has been consistently observed in obesity. Dopamine promotes GH release through activation of dopamine D2 receptors (D2Rs). Dopamine D2R availability in the brain is reduced in obese humans in proportion to body adiposity. We hypothesized that impaired dopamine D2R signaling is mechanistically involved in the deficient GH secretion associated with obesity. Objective: To test this hypothesis, we studied the effect of short-term bromocriptine (B) (a D2R agonist) treatment on spontaneous 24-h GH secretion in obese women, while body weight and caloric intake remained constant. Design: This was a prospective, fixed order, cross-over study. Setting: The study was performed in the Clinical Research Center at Leiden University Medical Center. Participants: There were 18 healthy obese women (body mass index 33.2 +/- 0.6 kg/m(2)) studied twice in the early follicular phase of their menstrual cycle. Intervention(s): Eight days of treatment with B and placebo (Pl) was performed. Main Outcome Measure(s): Blood was collected during 24 h at 10-min intervals for determination of GH concentrations. GH secretion parameters were calculated using deconvolution analysis. Results: Short-term treatment with B significantly enhanced diurnal GH secretion (Pl 121.4 +/- 16.4 vs. B 155.4 +/- 15.2 mug/liter(volume of distribution).24 h; P = 0.01), whereas IGF-I concentrations remained constant (Pl 22.4 +/- 2.4 vs. B 21.8 +/- 1.6 nmol/liter; P = 0.928). Conclusions: Activation of dopamine D2Rs by B favorably affects impaired nyctohemeral GH secretion in obese women. Reduced dopaminergic neuronal signaling might be involved in the pathogenesis of obesity associated hyposomatotropism.     

Central aortic pulsatile hemodynamics in obese premenopausal women

Obesity is a known risk factor for cardiovascular disease (CVD) but the mechanism by which obesity contributes to cardiovascular risk is not well understood. Arterial stiffness is a CVD risk factor associated with obesity. We studied 16 obese body mass index (BMI > 30) and 10 lean (BMI < 25) healthy premenopausal women. We measured fasting glucose, insulin, and lipids, blood pressure, and arterial tonometry to assess arterial stiffness. Obese women had higher glucose, insulin, total cholesterol and triglyceride levels, blood pressures, cardiac output, and peak flow. Characteristic impedance was lower (146 ± 31 [(dyne · s) · cm⁻⁵] vs. 187 ± 48 [(dyne · s) · cm⁻⁵]; P = .01), aortic diameter was greater (2.54 ± 0.20 cm vs. 2.29 ± 0.21 cm; P < .01), and peripheral pulse pressure was similar in obese compared with lean women. Obesity in premenopausal women is associated with increased cardiac output and peak aortic flow. Increased aortic diameter in obese women was associated with reduced characteristic impedance, potentially preventing an increase in peripheral pulse pressure despite elevated flow, which suggests proximal aortic remodeling. When aortic remodeling and compensation for increased hemodynamic demands are limited by environmental or genetic interference, hypertension or CVD may result.     

High circulating thyrotropin levels in obese women are reduced after body weight loss induced by caloric restriction

CONTEXT: Previous clinical studies concerning the impact of body weight loss on single plasma TSH concentration measurements or the TSH response to TRH in obese humans have shown variable results. OBJECTIVE: The objective of this study was to investigate the effect of weight loss induced by caloric restriction on diurnal TSH concentrations and secretion in obese humans. DESIGN: This was a clinical, prospective, crossover study. SETTING: The study was conducted at the Clinical Research Center of Leiden University Medical Center. PARTICIPANTS: Eleven obese premenopausal women (body mass index, 33.3 +/- 0.7 kg/m2) were studied. INTERVENTION: The study intervention was weight loss (50% reduction overweight by caloric restriction). MAIN OUTCOME MEASURE(S): Twenty-four-hour plasma TSH concentrations (10-min intervals) and the 24-h TSH secretion rate, calculated by a waveform-independent deconvolution technique (Pulse), were determined. RESULTS: The 24-h TSH secretion rate was significantly higher in obese women than in normal weight controls, and weight loss was accompanied by diminished TSH release (before weight loss, 43.4 +/- 6.4 mU/liter.24 h; after weight loss, 34.4 +/- 5.9 mU/liter.24 h; P = 0.02). Circulating free T3 levels decreased after weight loss from 4.3 +/- 0.19 to 3.8 +/- 0.14 pmol/liter (P = 0.04). Differences in 24-h TSH release correlated positively with the decline of circulating leptin (r2 = 0.62; P < 0.01). Conclusions: Elevated TSH secretion in obese women is significantly reduced by diet-induced weight loss. Among various physiological cues, leptin may be involved in this phenomenon. The decreases in TSH and free T3 may blunt energy expenditure in response to long-term calorie restriction, thereby frustrating weight loss attempts of obese individuals.     

Leptin response to oral glucose tolerance test in obese and nonobese premenopausal women

The objective of this study was to investigate the serum leptin response to oral glucose stimulation in a group of obese and nonobese normotensive, normolipidemic, and glucose-tolerant premenopausal women. Twenty-one obese (BMI: 37.7 +/- 6.3 kg/m2) and 14 nonbese (BMI: 21.5 +/- 1.0 kg/m2) age-matched, healthy premenopausal women were included in the study. Serum glucose, insulin, and leptin levels were measured at 30 min intervals during the 120 min of an oral glucose tolerance test (OGTT). Mean serum glucose, insulin, and leptin levels were significantly higher in the obese group compared to nonobese subjects during OGTT. Except for a 120 min decrement noted in obese women, no changes occurred in serum leptin levels during oral glucose stimulation in both groups. As a conclusion, absence of a significant elevation in serum leptin levels during OGTT in our obese subjects compared to nonobese subjects may be related to their normal metabolic variables despite being abdominally obese and insulin resistant.     

Plasma soluble tumor necrosis factor-alpha receptors circulate in proportion to leptin levels during the menstrual cycle in lean but not in obese women

OBJECTIVE: In recent studies serum leptin levels were significantly higher in the luteal phase than in the follicular phase, but the mechanism of changing leptin levels are unknown. Several research lines indicate a potential role for tumor necrosis factor (TNF-alpha) in ovulation and reproductive events. As TNF-alpha appears to regulate leptin secretion, we speculated that TNF-alpha might be involved in leptin variations during the menstrual cycle. DESIGN AND METHODS: Nine healthy never obese and ten overweight normally cycling women were studied. TNF-alpha action - through the plasma levels of the soluble fraction of the tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) - and leptin concentrations were measured in the follicular (F), peri-ovulatory (PO) and luteal phases (L) of their menstrual cycles. RESULTS: Circulating leptin levels were significantly associated with the stage of the menstrual cycle (P<0.001), being higher in PO and L phases. However, only three of ten overweight subjects vs eight of nine lean women (Chi square P=0.014 after Fisher's exact test) showed significantly higher leptin levels in the PO and L than in the F phase (95% confidence interval (95% CI) of the differences, 3.7 to 10.2 ng/ml, paired t-test P=0.001). In these women (group 1), the changes in leptin levels parallelled the variations observed in plasma sTNFR1 (2.50+/-0.1 vs 2.11+/-0.05 ng/ml, P<0.0001, 95% CI, 0.21 to 0.56) and sTNFR2 levels (5.19+/-0.28 vs 4.55+/-0.25 ng/ml, P<0.0001, 95% CI, 0. 47 to 0.81). In the remaining women (group 2), leptin (95% CI, -1 to 9.2 ng/ml, P=not significant (NS)), sTNFR1 (95% CI, -0.3 to 0.14 ng/ml, P=NS) and sTNFR2 levels (95% CI, -0.95 to 0.39 ng/ml, P=NS) were essentially unaltered throughout the menstrual cycle. Group 2 women were similar in age (36.1+/-2.9 vs 37.3+/-1.4 years) and significantly overweight (body mass index 31+/-2.9 vs 23.9+/-1. 2 kg/m(2)) compared with group 1 women. A negative correlation was observed between leptin levels in the follicular phase and the change in plasma leptin from F to L phase in all subjects (r=-0.67, P=0.002). CONCLUSIONS: Circulating leptin and sTNFRs levels change significantly during the menstrual cycle of most lean women. In contrast, the levels of these molecules remain essentially unaltered during the F, PO and L phases in the majority of overweight women. Obesity might be associated not only with blunted diurnal excursions and dampened pulsatility, but also with blunted excursions during the menstrual cycle.     

Inhibition of cortisol biosynthesis decreases circulating leptin levels in obese humans

CONTEXT: Glucocorticoids increase both appetite and leptin secretion; the hyperleptinemic effect might be a counterregulatory response to the orexigenic effect of glucocorticoids. However, the effect of glucocorticoid inhibition on leptin production has not been reported. OBJECTIVE: We tested the hypothesis that if glucocorticoid-induced hyperleptinemia plays a physiological role, then inhibition of endogenous cortisol biosynthesis should decrease leptin secretion. DESIGN: A randomized, placebo-controlled, cross-over study design was used. SETTING: The study was carried out at a General Clinical Research Center. PARTICIPANTS: Eight obese subjects (four men, four women; mean age, 30.4 +/- 1.56 yr; mean body mass index, 42.0 +/- 1.33 kg/m2) participated in the study. Intervention: The subjects were treated with metyrapone (750 mg every 4 h) or placebo for 24 h during two overnight admissions, 2 wk apart. Blood sampling for measurement of cortisol, leptin glucose, insulin, and C-peptide was performed hourly for 6 h and every 2 h for 24 h. MAIN OUTCOME MEASURE: The change in plasma leptin from baseline during metyrapone vs. placebo treatment was measured. RESULTS: Metyrapone treatment was associated with a significant decrease in plasma cortisol level; the cortisol nadir was 4.84 +/- 1.22 microg/dl during placebo and 2.80 +/- 0.65 microg/dl during metyrapone treatment (P = 0.009). Compared with placebo, metyrapone treatment was associated with a significant reduction in circulating leptin levels and marked attenuation of the nocturnal rise in plasma leptin (+28.45 +/- 11.12% vs. +55.51 +/- 5.42%; P = 0.01). CONCLUSIONS: We conclude that metyrapone-induced inhibition of cortisol biosynthesis results in hypoleptinemia, which indicates that glucocorticoids may play an important role in the physiological regulation of leptin.     

Marked diurnal variation in urinary excretion of pyridinium cross-links in premenopausal women.

To investigate whether bone resorption exhibits a diurnal variation in healthy premenopausal women, we measured urinary excretion of pyridinoline and deoxypyridinoline cross-links (U-Pyr/Cr and U-D-Pyr/Cr) every 3 h over a 24-h period in 12 healthy premenopausal women (mean +/- 1 SD age, 32 +/- 5 yr). To study diurnal variation, U-Pyr/Cr and U-D-Pyr/Cr are the best available markers of bone resorption for a diurnal variation study, as they are not influenced by diet. Plasma osteocalcin and serum alkaline phosphatase (markers of bone formation) were also measured. A marked diurnal rhythm was observed in U-Pyr/Cr and U-D-Pyr/Cr, with the peak between 0500-0800 h and the nadir between 1400-2300 h. The fluctuation was 2-fold over the 24-h period, with a mean fall of 25-35% between 0800-1100 h. This study demonstrates a marked diurnal variation in the new biochemical markers of bone resorption, U-Pyr/Cr and U-D-Pyr/Cr, in premenopausal women. Furthermore, this study emphasizes the importance of regulating the time of the urine sample taken for measuring urinary pyridinium cross-links for clinical investigations as well as in clinical practice.     

Smoking habits and circulating leptin in postmenopausal non-obese women

This study examined whether smoking habits affect the correlation between serum leptin levels and body mass index (BMI) in 101 postmenopausal Caucasian non-obese women, all aged 57-59years. Mean serum leptin level in the entire group was 19.8 +/- 12.3 ng/ml (mean +/- s.d.) and mean BMI was 25.3 +/- 3.5 kg/m2. These parameters correlated significantly to each other (r = 0.70, p < 0.001). Between those who have smoked regularly for more than 2 years (n = 26) and those who are ex-smokers or have never smoked (n = 75), serum leptin levels or BMI did not differ and the correlation between serum leptin and BMI was identical. This suggests that smoking habits do not influence circulating leptin in Caucasian postmenopausal non-obese women.     

Urinary albumin excretion is independently associated with C-reactive protein levels in overweight and obese nondiabetic premenopausal women

OBJECTIVES: C-reactive protein (CRP) and microalbuminuria are nowadays considered markers of chronic inflammation of the arterial wall and of endothelial dysfunction, respectively. An increase of CRP levels and of urinary albumin excretion (UAE) rate have both been reported to be independently associated with a higher risk of cardiovascular morbidity and mortality in the general population. The aim of the present study was to evaluate the possible correlation between UAE and CRP concentrations in overweight and obese premenopausal women. DESIGN AND SETTING: A cross-sectional study in a primary care setting. SUBJECTS, MAIN OUTCOME MEASURES: CRP levels and UAE rate were measured in 103 overweight and obese premenopausal women, aged 18-45 years. Other measurements included: central fat accumulation, as evaluated by waist circumference, insulin resistance, as calculated by homeostatic model assessment (HOMAIR); fat-free mass (FFM), as measured by bioimpedance analysis; blood pressure; and fasting plasma levels of glucose, insulin, and lipids. RESULTS: Urinary albumin excretion was positively correlated with body mass index (BMI) (P < 0.01), waist circumference (P < 0.001), diastolic blood pressure (P < 0.01), triglycerides (P < 0.01), HOMAIR (P < 0.05), and CRP levels (P < 0.05); and negatively associated with HDL cholesterol (P < 0.001). After multivariate analysis, diastolic blood pressure, HDL cholesterol, and CRP levels maintained their significant correlation with UAE. CONCLUSION: Our study shows a strong relationship between UAE and CRP concentrations, irrespective of age and other anthropometric and metabolic variables. On this basis, it can be argued that inflammation of the arterial wall, as indicated by higher CRP plasma levels, and endothelial dysfunction, as shown by higher UAE rate, might represent simultaneous phenomena in the development of atherosclerosis in overweight and obese premenopausal women.     

活动期肢端肥大症患者TSH分泌减少且不规则但仍有昼夜节律

肢端肥大症患者常合并甲状腺肿,其大小与生长激素分泌过量的时间长短有关.有些可演变为有自主分泌功能的结节性甲状腺肿,但显性甲状腺功能亢进则罕见.     

Alcohol ingestion decreases both diurnal and nocturnal secretion of leptin in healthy individuals

OBJECTIVE: Neuropeptide Y (NPY) stimulates appetite and increases food intake. Leptin inhibits NPY. It is not known whether alcohol influences any of these factors, but it has been suggested that alcohol stimulates appetite in man. The primary objective of this investigation was to determine whether ingestion of ethanol inhibits leptin secretion in normal subjects. SUBJECTS AND DESIGN: Fourteen healthy, non-obese subjects of both sexes (7 F/7 M) were included. They were divided into two groups (I and II; 8/6). All were investigated on two occasions. On one occasion alcohol was ingested, and on the other drinking water was given. The experiments took place in random order, one week apart. In group I two experiments (A = alcohol; B = water) were performed during the day. In group II the experiments were carried out during the night (C = alcohol; D = water). Each alcoholic drink contained 0.45 g ethanol/kg. The drinks were given at 08.00, 09.30 and 11.00 hours in experiments A and B, and at 18.00, 20.00 and 22.00 hours in experiments C and D. Venous blood samples were collected before, during and after the drinks over periods of 6 h in group I and 14 h in group II. MEASUREMENTS: Serum concentrations of leptin, insulin-like growth factor 1 (IGF-1), IGF binding protein 1 (IGFBP-1), insulin, cortisol, testosterone, ethanol and plasma glucose were determined. RESULTS Group I serum leptin levels declined during the day in both men and women regardless of whether alcohol or water had been administered in the morning. Since leptin levels in general were markedly higher in women than in men, all leptin changes after water/alcohol were transformed to percentage changes to make them comparable between sexes. When the percentage leptin decline over a 6-h period (08.00-24.00 hours) was expressed by a decremental area under curve (AUC08-14), it became evident that alcohol inhibited leptin secretion, inasmuch as the leptin decremental area, obtained after alcohol, was significantly larger than the one obtained after water (124 +/- 17 vs. 57 +/- 8; P < 0.01). Similar insulin and glucose levels were obtained after alcohol and water. Group II serum leptin levels increased after both alcohol and water during the initial part of the night (18.00-20.00 hours). In this period alcohol inhibited the secretion of leptin as shown by the leptin incremental area (AUC18-24) which was 53 +/- 18 after alcohol and 113 +/- 15 after water (P < 0.01). As the ethanol concentration in serum began to fall, its inhibitory effect on leptin gradually disappeared, and when leptin AUCs representing the entire night were determined after alcohol and water, they were not significantly different. Similar insulin, glucose, testosterone, IGF-1 and cortisol levels were found after alcohol and water. The IGFBP-1 level increased, but not significantly so until 6 h after commencing the alcohol ingestion. CONCLUSION: Ingestion of moderate amounts of alcohol has an inhibitory effect on leptin secretion in normal subjects. The effect may be direct rather than indirect, since several factors known to affect leptin are not influenced by alcohol. It is tempting to speculate that alcohol might serve as an appetizer by decreasing leptin secretion, but additional studies are necessary to prove that hypothesis since previous studies have shown that leptin has a long-term rather than an acute effect on hunger.