Secretory patterns of leptin and luteinizing hormone in food-restricted young female sheep

Leptin, the product of the ob gene, has been proposed as a metabolic signal that regulates the secretion of GnRH/LH. This may be critical during prepubertal development to synchronize information about energy stores and the secretion of GnRH/LH. This study aimed to assess the effect of food restriction on the episodic secretion of leptin and LH in young female sheep. Five 20-week-old prepubertal females were fed a low-level diet for 10 weeks to maintain the body weight. Control females of the same age received food ad libitum. Blood samples were collected at 10-min intervals for six hours at 20, 26, and 30 weeks of age, and plasma leptin, LH, insulin and cortisol concentrations were measured. In the control group, no changes were found in pulsatile LH secretion characteristics. Mean LH concentrations and LH amplitude were lower in the food-restricted group than in the control group at 26 and 30 weeks of age. In the control group, pulsatile leptin secretion did not change. When compared to control lambs of the same age, the food-restricted group showed lower mean plasma leptin concentrations, pulse amplitude and plasma insulin levels, after 6 weeks of restriction (week 26), although by week 30, plasma leptin concentrations and plasma insulin rose to those of the control group. Leptin pulse frequency did not change, nor did mean plasma levels of insulin in the control group at any age studied. Mean plasma concentration of cortisol did not change within or between groups. These data suggest that plasma leptin concentrations may not be associated with the onset of puberty under regular feeding and natural photoperiod in lambs. Prolonged food restriction, however, induces metabolic adaptations that allow an increase of leptin during the final period, probably related to the development of some degree of insulin resistance.     

Retention of estradiol negative feedback relationship to LH predicts ovulation in response to caloric restriction and weight loss in obese patients with polycystic ovary syndrome

The present study tests the hypothesis that specific endocrine, metabolic, and anthropometric features distinguish obese women with polycystic ovary syndrome (PCOS) who resume ovulation in response to calorie restriction and weight loss from those who do not. Fifteen obese (body mass index 39 +/- 7 kg/m(2)) hyperandrogenemic oligoovulatory patients undertook a very low calorie diet (VLCD), wherein each lost > or =10% of body weight over a mean of 6.25 mo. Body fat distribution was quantitated by magnetic resonance imaging. Hormones were measured in the morning at baseline, after 1 wk of VLCD, and after 10% weight loss. To monitor LH release, blood was sampled for 24 h at 10-min intervals before intervention and after 7 days of VLCD. Responders were defined a priori as individuals exhibiting two or more ovulatory cycles in the course of intervention, as corroborated by serum progesterone concentrations > or =18 nmol/l followed by vaginal bleeding. At baseline, responders had a higher sex hormone-binding globulin (SHBG) concentration but were otherwise indistinguishable from nonresponders. Body weight, the size of body fat depots, and plasma insulin levels declined to a similar extent in responders and nonresponders. Also, SHBG increased, and the free testosterone index decreased comparably. However, responders exhibited a significant decline of circulating estradiol concentrations (from 191 +/- 82 to 158 +/- 77 pmol/l, means +/- SD, P = 0.037) and a concurrent increase in LH secretion (from 104 +/- 42 to 140 +/- 5 U.l(-1).day(-1), P = 0.006) in response to 7 days of VLCD, whereas neither parameter changed significantly in nonresponders. We infer that evidence of retention of estradiol-dependent negative feedback on LH secretion may forecast follicle maturation and ovulation in obese patients with PCOS under dietary restriction.     

Antiandrogenic contraceptives increase serum adiponectin in obese polycystic ovary syndrome patients

Increasing evidence suggests that adipocyte function is altered in the polycystic ovary syndrome (PCOS) as a result of androgen excess, providing an explanation for its frequent association with abdominal adiposity and insulin resistance. We here compared the response of serum adiponectin and leptin levels to the amelioration of androgen excess by means of treatment with an antiandrogenic oral contraceptive pill, as compared with the response to insulin sensitization with metformin. Thirty-four women presenting with PCOS were randomized to treatment with an oral contraceptive containing 35 microg ethinyl-estradiol plus 2 mg cyproterone acetate (Diane(35) Diario) or with metformin (850 mg twice daily). Serum adiponectin and leptin levels were evaluated at baseline and after 12 and 24 weeks of treatment. In obese PCOS women, treatment with Diane(35) Diario resulted in an increase in serum adiponectin levels and in the adiponectin/leptin ratio, in parallel with a marked decrease in serum androgen concentrations, whereas no statistically significant changes were observed during treatment with metformin. On the contrary, leptin concentrations did not show any statistically significant change during the study with any of the drugs studied here. In summary, our present results might suggest a direct inhibitory effect of androgen excess on adiponectin secretion by adipocytes in obese PCOS women, supporting the hypothesis that androgen excess contributes to adipocyte dysfunction in these women.     

Leptin treatment markedly increased plasma adiponectin but barely decreased plasma resistin of ob/ob mice

Adiponectin (ApN) and leptin are two adipocytokines that control fuel homeostasis, body weight, and insulin sensitivity. Their interplay is still poorly studied. These hormones are either undetectable or decreased in obese, diabetic ob/ob mice. We examined the effects of leptin treatment on ApN gene expression, protein production, secretion, and circulating levels of ob/ob mice. We also briefly tackled the influence of this treatment on resistin, another adipocytokine involved in obesity-related insulin resistance. Leptin-treated (T) obese mice (continuous sc infusion for 6 days) were compared with untreated lean (L), untreated obese (O), and untreated pair-fed obese (PF) mice. Blood was collected throughout the study. At day 3 or day 6, fat pads were either directly analyzed (mRNA, ApN content) or cultured for up to 24 h (ApN secretion). The direct effect of leptin was also studied in 3T3-F442A adipocytes. Compared with L mice, ApN content of visceral or subcutaneous fat and ApN secretion by adipose explants were blunted in obese mice. Accordingly, plasma ApN levels of O mice were decreased by 50%. Leptin treatment of ob/ob mice increased ApN mRNAs, ApN content, and secretion from the visceral depot by 50-80%. Leptin also directly stimulated ApN mRNAs and secretion from 3T3-F442A adipocytes. After 6 days of treatment, plasma ApN of ob/ob mice increased 2.5-fold, a rise that did not occur in PF mice. Plasma resistin of T mice was barely decreased. Leptin treatment, but not mere calorie restriction, corrects plasma ApN in obese mice by restoring adipose tissue ApN concentrations and secretion, at least in part, via a direct stimulation of ApN gene expression. Such a treatment only minimally affects circulating resistin. ApN restoration could, in concert with leptin, contribute to the metabolic effects classically observed during leptin administration.     

Effects of chronic food restriction and treatments with leptin or ghrelin on different reproductive parameters of male rats

The existence of a close relationship between energy status and reproductive function is well-documented, especially in females, but its underlying mechanisms remain to be fully unfolded. This study aimed to examine the effects of restriction of daily calorie intake, as well as chronic treatments with the metabolic hormones leptin and ghrelin, on the secretion of different reproductive hormones, namely pituitary gonadotropins and prolactin, as well as testosterone, in male rats. Restriction (50%) in daily food intake for 20 days significantly reduced body weight as well as plasma PRL and T levels, without affecting basal LH and FSH concentrations and testicular weight. Chronic administration of leptin to rats fed ad libitum increased plasma PRL levels and decreased circulating T, while it did not alter other hormonal parameters under analysis. In contrast, in rats subjected to 50% calorie restriction, leptin administration increased plasma T levels and reduced testis weight. Conversely, ghrelin failed to induce major hormonal changes but tended to increase testicular weight in fed animals, while repeated ghrelin injections in food-restricted males dramatically decreased plasma LH and T concentrations and reduced testis weight. In sum, we document herein the isolated and combined effects of metabolic stress (50% food restriction) and leptin or ghrelin treatments on several reproductive hormones in adult male rats. Overall, our results further stress the impact and complex way of action of different metabolic cues, such as energy status and key hormones, in reproductive function also in the male.     

Sex hormone-binding globulin and female reproductive function

Although sex steroids have long been known to influence serum concentrations of SHBG, it is now recognized that nutritional factors may be more important in the regulation of SHBG in women. Thus, SHBG concentrations are negatively correlated with body mass index (BMI) and, more particularly, to indices of central adiposity. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is associated with truncal obesity, hyperandrogenism and hyperinsulinaemia. There is evidence that insulin may be the humoral mediator of the weight-dependent changes in SHBG. Serum SHBG concentrations are inversely correlated with both fasting and glucose-stimulated insulin levels, and insulin has been shown to have a direct inhibitory effect on SHBG synthesis and secretion by hepatocytes in culture. However, the interrelationship of BMI, insulin and SHBG appears to be different in women with PCOS from that in normal subjects. The clinical importance of the weight-related suppression of SHBG is illustrated by the finding of a greater prevalence of hirsutism in obese women with PCOS compared with their lean counterparts. Obese subjects with PCOS have similar total testosterone concentrations to lean PCO women but have lower SHBG and reciprocally higher free testosterone levels. Calorie restriction results in reduction of serum insulin followed by an increase in SHBG and a fall in free testosterone but an isocaloric, low-fat diet has no significant effect on SHBG concentrations. Weight reduction in obese, hyperandrogenaemic women with PCO is an important approach to the management of both anovulation and hirsutism.     

Anti-Mullerian hormone levels reflect severity of PCOS but are negatively influenced by obesity: relationship with increased luteinizing hormone levels

The objective of the study was the comparison of anti-Müllerian hormone (AMH) levels among obese or overweight and normal-weight women with the four different polycystic ovary syndrome (PCOS) phenotypes and healthy control subjects. AMH levels were evaluated in four age- and body mass index (BMI)-matched groups of 25 normal-weight and 25 obese or overweight women each, belonging to the four main subsets of the syndrome resulting from combinations of the three diagnostic criteria [group 1: oligo- and/or anovulation (ANOV), hyperandrogenemia (HA), and polycystic ovaries (PCO) on ultrasonographic evaluation; group 2: ANOV and HA; group 3: HA and PCO, group 4: ANOV and PCO], and in 50 (25 obese or overweight and 25 normal weight) age- and BMI-matched healthy control subjects. Age, BMI, waist circumference, FSH, LH, prolactin, testosterone, Delta(4)-androstenedione, dehydroepiandrosterone-sulfate, 17alpha-OH-progesterone, fasting insulin, glucose, AMH, free androgen index, and homeostasis model assessment for insulin resistance index were analyzed. AMH levels were significantly higher in PCOS groups 1 and 2 compared with groups 3 and 4 and the control group and higher in PCOS groups 3 and 4 compared with the control group. AMH levels were significantly increased in normal-weight compared with obese and overweight women. AMH concentrations were independently predicted, in order of significance, by LH and testosterone levels, BMI (negatively), and the total number of follicles 2-9 mm in diameter. The differences in circulating AMH levels between the main phenotypic groups of PCOS women appear to reflect the severity of the syndrome, but are negatively affected by obesity. Increased LH levels might be the most significant independent link between PCOS-associated disorders of ovulation and the observed increase in circulating AMH concentration.     

Glucose ingestion acutely lowers pulsatile LH and basal testosterone secretion in men

Chronic hyperglycemia inhibits the male gonadal axis. The present analyses test the hypothesis that acute glucose ingestion also suppresses LH and testosterone (T) secretion and blunts the LH-T dose-response function. The design comprised a prospectively randomized crossover comparison of LH and T secretion after glucose vs. water ingestion in a Clinical Translational Research Center. The participants were healthy men (n = 57) aged 19-78 yr with body mass index (BMI) of 20-39 kg/m(2). The main outcome measurements were deconvolution and LH-T dose-response analyses of 10-min data. LH-T responses were regressed on glucose, insulin, leptin, adiponectin, age, BMI, and CT-estimated abdominal visceral fat. During the first 120 min after glucose ingestion, for each unit decrease in LH concentrations, T concentrations decreased by 86 (27-144) ng/dl (r = 0.853, P < 0.001). Based upon deconvolution analysis, glucose compared with water ingestion reduced 1) basal (nonpulsatile; P < 0.001) and total (P < 0.001) T secretion without affecting pulsatile T output and 2) pulsatile (P = 0.043) but not basal LH secretion. By multivariate analysis, pulsatile LH secretion positively predicted basal T secretion after glucose ingestion (r = 0.374, P = 0.0042). In addition, the glucose-induced fall in pulsatile LH secretion was exacerbated by higher fasting insulin concentrations (P = 0.054) and attenuated by higher adiponectin levels (P = 0.0037). There were no detectable changes in the analytically estimated LH-T dose-response curves (P > 0.30). In conclusion, glucose ingestion suppresses pulsatile LH and basal T secretion acutely in healthy men. Suppression is influenced by age, glucose, adiponectin, and insulin concentrations.     

Central infusion of recombinant ovine leptin normalizes plasma insulin and stimulates a novel hypersecretion of luteinizing hormone after short-term fasting in mature beef cows

The present studies tested the hypotheses that short-term fasting would reduce leptin gene expression and circulating concentrations of leptin and insulin in mature, ovariectomized, estradiol-implanted cows and that intracerebroventricular infusions of recombinant ovine leptin (oleptin) would attenuate reductions in insulin concentration and stimulate LH secretion. Ovariectomized cows were assigned to either control (normal fed; n = 6) or fasted (60 h of fasting; n = 7) groups and infused with 200 microg recombinant oleptin three times at hourly intervals on Day 2 (n = 6 per group). Fasting decreased plasma concentrations of insulin (P < 0.01) and leptin (P < 0.04) but, as expected, did not reduce plasma concentrations of glucose or any LH secretion variable. Central infusion of leptin on Day 2 increased (P < 0.01) plasma concentrations of leptin in both control and fasted groups. Concomitantly, leptin treatment increased plasma insulin (P < 0.01) and LH (P < 0.03) concentrations in fasted but not in control cows. Increases in overall mean and baseline concentrations of LH after leptin treatment were the result of an augmentation of the size of LH pulses. The effects of fasting on leptin gene expression and the potential diurnal effects on circulating leptin were examined in a group of cows (n = 12) not treated with leptin. Fasting for 60 h reduced (P < 0.001) leptin gene expression by 30%, and no diurnal effects on circulating leptin were observed. These results indicate that although short-term fasting does not reduce the frequency or amplitude of LH pulses or the concentration of LH in mature cows, this nutritional perturbation clearly sensitizes both the hypothalamic-pituitary axis and endocrine pancreas to exogenous leptin, which in these experiments resulted in heightened secretion of both LH and insulin.     

Body reserves affect the reproductive endocrine responses to an acute change in nutrition in mature male sheep

Metabolic status is a powerful regulator of reproductive activity, but the metabolic mediators involved and the relationships between fat reserves, food intake and the systems that control reproduction are not fully understood. In this study with mature male Merino sheep, we tested whether the effect of an acute nutritional stimulus on pulsatile LH secretion depended on body condition. Two groups of rams ("Fat" and "Lean") were fed differentially for 4 months to achieve high or low levels of body mass and body condition score. Half of each group was then assigned to be fed either their maintenance requirement or twice their maintenance requirement and, 7 days later, plasma samples were collected every 20 min for 24 h. All samples were used for the analysis of LH pulses and pooled samples were used for the measurement of metabolic hormone concentrations. In the rams that were fed the maintenance diet, the frequency of LH pulses was similar for the Fat and Lean groups, but plasma concentrations of leptin and insulin were significantly higher in the Fat group than in the Lean group. Following an acute increase in food intake, plasma concentrations of insulin were significantly increased in both Fat and Lean rams, but plasma leptin concentrations were increased only in Fat rams and LH pulse frequency was increased only in Lean rams. We concluded that the secretion of LH and leptin, but not insulin, is differentially influenced by nutritional status and body condition and that the role of leptin in the central regulation of the GnRH-LH system is probably permissive.     

Relationship between plasma leptin and zinc levels and the effect of insulin and oxidative stress on leptin levels in obese diabetic patients

Leptin is thought to be a lipostatic signal that contributes to body weight regulation. Zinc plays an important role in appetite regulation also. Our aim is to evaluate the relationship between leptin and zinc in obese and nonobese type 2 diabetic patients and its relationship with oxidative stress and insulin. We studied 25 nonobese nondiabetic women (controls); 35 nonobese diabetic women; and 45 obese diabetic women. Plasma leptin concentration was determined by immunoradiometric assay. Thiobarbituric acid reactive substances (TBARS), markers of oxidative stress, were assayed by the spectrofotometric method. Plasma levels of zinc and insulin were measured by atomic absorption spectrophotometer and electrochemiluminescence methods, respectively. We found that nonobese diabetic patients had significantly lower zinc and higher TBARS levels than control subjects (P<0.01). There was no difference in plasma leptin levels between nonobese diabetic subjects and controls. Obese diabetic subjects had significantly higher plasma leptin, TBARS, and insulin levels and significantly lower plasma zinc levels than nonobese diabetic subjects (for each comparison; P<0.01). The univariate and multivariate analyses demonstrated a significant positive correlation between leptin and body mass index (P<0.01) and insulin (P<0.01), and a significant negative correlation between leptin and zinc in obese subjects. Additionally, TBARS levels was positive correlated with insulin and negative correlated with zinc in obese diabetic subjects. We conclude that zinc may be a mediator of the effects of leptin, although the detailed mechanism is still unknown and requires further investigation. Free radical induced mechanism(s) may be involved in this process.     

Plasma level of calcitonin gene-related peptide in patients with polycystic ovary syndrome and its relationship to hormonal and metabolic parameters

The aim of the study was to evaluate the plasma level of calcitonin gene-related peptide (CGRP) in patients with polycystic ovary syndrome (PCOS) and its relationship to hormonal and metabolic parameters. We also observed the effect of CGRP on testosterone (T) and estradiol (E(2)) release in cultured human granulosa cells. PCOS subjects (n=215) and matched healthy control women (n=103) at age of 22-38 years were enrolled in this study. We analyzed plasma CGRP concentrations, relationship of plasma CGRP with insulin resistance (IR), body mass index (BMI), luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio and T. The T and E(2) release levels of cultured human granulosa cells treated by CGRP were also measured. The results showed that plasma CGRP concentrations were significantly higher in women with PCOS than those of control subjects. In women with PCOS, there was a strong positive correlation between the plasma CGRP level with HOMA-IR, AUC-insulin, AUC-glucose, the ratio of LH/FSH and plasma T concentration. Human granulosa cells expressed CGRP receptor. Exogenous CGRP caused an elevation of T and E(2) released from the human granulosa cells. These findings suggest that CGRP may participate in the pathophysiological process of PCOS.     

Association between Serum Leptin Levels and 24‐Hour Blood Pressure in Obese Women

Objective: To assess the relationship between serum leptin and 24‐hour blood pressure (BP) in obese women, according to body fat distribution. Research Methods and Procedures: A cross‐sectional study was carried out in a population of 70 nondiabetic, normotensive, obese women (40 with android and 30 with gynoid type of obesity) and 20 nonobese healthy women as a control group. All subjects underwent 24‐hour ambulatory BP monitoring. Blood samples were collected for serum leptin and plasma insulin measurements. Total cholesterol and high‐density lipoprotein cholesterol were also measured. Results: Serum leptin levels were significantly higher in obese subjects than in controls, and they were more elevated in android obese women than in gynoid ones. Leptin levels were positively related to body mass index (BMI), insulin, and waist and hip circumferences in the android group. Among gynoid subjects, leptin levels showed positive associations with BMI and insulin. In women with android obesity, strong positive correlations (p < 0.001) were found between leptin levels and 24‐hour systolic BP (SBP), daytime SBP, nighttime SBP, 24‐hour diastolic BP (DBP), and daytime DBP. Multiple regression analyses, including age, insulin and leptin concentrations, BMI, and waist and hip circumferences on 24‐hour and daytime SBP and DBP, showed that only leptin levels contributed to the variability of BP. Conclusions: Our study shows that serum leptin levels are directly related to 24‐hour BP levels in normotensive women with android fat distribution, independently of BMI.     

The influence of very-low-calorie-diet on serum leptin, soluble leptin receptor, adiponectin and resistin levels in obese women

The aim of our study was to determine whether adipocyte-derived hormones leptin, adiponectin and resistin contribute to the improvement of insulin sensitivity after very-low calorie diet (VLCD). Therefore, serum levels of these hormones were measured in fourteen obese females before and after three weeks VLCD and in seventeen age- and sex-matched healthy controls. Body mass index, HOMA index, serum insulin and leptin levels in obese women before VLCD were significantly higher than in control group (BMI 48.01+/-2.02 vs. 21.38+/-0.42 kg/m(2), HOMA 10.72+/-2.03 vs. 4.69+/-0.42, insulin 38.63+/-5.10 vs. 18.76+/-1.90 microIU/ml, leptin 77.87+/-8.98 vs. 8.82+/-1.52 ng/ml). In contrast, serum adiponectin and soluble leptin receptors levels were significantly lower in obese women before VLCD than in the control group. No differences were found in serum glucose and resistin levels between the obese group before VLCD and the control group. VLCD significantly decreased BMI, HOMA index, serum glucose, insulin and leptin levels and increased soluble leptin receptor levels. The changes in serum adiponectin and resistin levels in obese women after VLCD did not reach statistical significance. We conclude that leptin and soluble leptin receptor levels were affected by VLCD while adiponectin and resistin concentrations were not. Therefore, other mechanisms rather than changes in the endocrine function of the adipose tissue are probably involved in the VLCD-induced improvement of insulin sensitivity.     

Divergent effects of leptin on luteinizing hormone and insulin secretion are dose dependent

We have shown recently that fasting permits leptin to modulate both luteinizing hormone (LH) and insulin secretion in cows. In rodents, leptin causes divergent effects on LH and insulin release that are dose dependent. To test the hypothesis that leptin effects on LH and insulin secretion in fasted cows are dose related, we examined the effects of various doses of recombinant ovine leptin (oleptin) in mature cows. Twenty ovariectomized beef cows, each bearing an estradiol implant to maintain basal estradiol concentrations, were used. All cows were fasted for 60 hr with free access to water and were assigned randomly to one of four groups (n = 5/group): 1) saline control; 2) leptin, 0.2 microg/kg; 3) leptin, 2.0 microg/kg; and 4) leptin, 20 microg/kg body wt. Blood samples were collected at 10-min intervals for 6 hr on Days 0 and 2, with saline or oleptin injected intravenously immediately after the first intensive sample on Day 2 (54 hr). Leptin caused a dose-related increase (P < 0.001) in mean concentrations of circulating LH. Stimulation of LH release by leptin was significant at the lowest (141% of control) and middle (122% of control) doses used, but no increase was observed for the highest dose. Increased mean concentrations of LH appeared to result from an augmentation of basal secretion, as pulse characteristics were not affected. After 54 hr of fasting, plasma insulin concentrations were lowered (P < 0.01) in all treatment groups compared to Day 0. After leptin injections, plasma insulin concentrations increased (P < 0.01) and reached highest concentrations during the first hour of sampling. However, this increase was sustained for several hours only in the intermediate (2.0 microg/kg) dose group. Collectively, our results show that leptin has potent positive effects on both LH and insulin secretion in fasted cows, but the anterior pituitary and endocrine pancreas appear to become downregulated in the presence of excess ligand.     

Plasma glucagon response to intravenous alanine in obese and non-obese subjects

To investigate glucagon (IRG) and insulin (IRI) responses to alanine infusion in obesity and to assess the effect of body weight reduction with respect to hormonal balance, we compared six obese subjects with nine normal weight controls. None of the subjects were diabetic by OGTT criteria. Plasma IRI and IRG were measured following IV alanine at a rate of 0.1 g/kg over a period of 2 min. Our obese subjects had an increase in IRG response to alanine, which was due to decreased suppression of alpha-cell function due to insulin resistance. Weight reduction via calorie restriction reduced insulin demand, resulting in reduced plasma IRI by restoring beta-cell function, and the IRG response was paradoxically decreased as compared with that before weight loss. It is conceivable that improvements in insulin sensitivity after body weight reduction may re-establish the normalization of pancreatic beta-cell function and the insulin-induced inhibition of IRG secretion. Our obese subjects were characterized by decreased IRG secretion which was reflected in a change in body weight reduction.     

Circadian rhythm of blood leptin level in obese and non-obese people

Leptin, an adipose tissue hormone, has circadian variations in its secretion. Aims of this study were to show how circadian rhythm depends on fat tissue distribution in obese and non-obese subjects. The research was carried out on 70 subjects (37 men and 33 women) with an average body mass index (BMI) of 25.22 kg/m2. Concentration of leptin in blood was measured at 8.30 a.m., 12.30 p.m. and 6.30 p.m. Basal leptin level correlated strongly with all isolated regions of subcutaneous fat tissue in women and obese subjects. Circadian changes of blood leptin level in non-obese people are more significant than these changes in obese people. Differences in circadian pattern of leptin secretion between obese and non-obese subjects were probably caused by enlarged volume of subcutaneous fat tissue in obese people. Lean subjects have subcutaneous fat in physiological range which allows influence of some hormones (insulin or cortizol) or food intake on leptin secretion.     

BMI Is the Main Determinant of the Circulating Leptin in Women after Vertical Banded Gastroplasty

Objective: To assess the main determinant of serum leptin concentration changes in morbidly obese patients treated by banded vertical gastroplasty. Research Methods and Procedures: Serum leptin and insulin concentrations, insulin resistance, BMI, body weight, and body fat mass in 18 obese women and 8 obese men treated by vertical banded gastroplasty were studied. Lean women and men subjects were used as controls. Results: Before surgery, serum leptin and insulin concentrations and insulin resistance index were significantly higher in morbidly obese patients than in control subjects. BMI, body fat mass, and serum triacylglycerol concentrations were also significantly higher in obese than in lean subjects. All of these parameters gradually decreased during 50 weeks after surgery. Univariate regression analysis displayed significant correlations between the following: serum leptin concentration and BMI (and body fat mass), serum leptin concentration and serum insulin concentration, and serum leptin concentration and insulin resistance index. Multivariate regression analysis indicated that only BMI was independently correlated with the decrease in serum leptin concentration. Discussion: Obtained data suggest the following: 1) vertical banded gastroplasty causes reduction of body weight, serum leptin and insulin concentration, insulin resistance, and serum triacylglycerol concentration; and 2) BMI is the main determinant of the circulating leptin concentration in morbidly obese women after anti‐obesity surgery.     

Amylin improves the effect of leptin on insulin sensitivity in leptin-resistant diet-induced obese mice

Leptin enhances insulin sensitivity in addition to reducing food intake and body weight. Recently, amylin, a pancreatic β-cell-derived hormone, was shown to restore a weight-reducing effect of leptin in leptin-resistant diet-induced obesity. However, whether amylin improves the effect of leptin on insulin sensitivity in diet-induced obesity is unclear. Diet-induced obese (DIO) mice were infused with either saline (S), leptin (L; 500 μg·kg?1·day?1), amylin (A; 100 μg·kg?1·day?1), or leptin plus amylin (L/A) for 14 days using osmotic minipumps. Food intake, body weight, metabolic parameters, tissue triglyceride content, and AMP-activated protein kinase (AMPK) activity were examined. Pair-feeding and weight-matched calorie restriction experiments were performed to assess the influence of food intake and body weight reduction. Continuous L/A coadministration significantly reduced food intake, increased energy expenditure, and reduced body weight, whereas administration of L or A alone had no effects. L/A coadministration did not affect blood glucose levels during ad libitum feeding but decreased plasma insulin levels significantly (by 48%), suggesting the enhancement of insulin sensitivity. Insulin tolerance test actually showed the increased effect of insulin in L/A-treated mice. In addition, L/A coadministration significantly decreased tissue triglyceride content and increased AMPKα2 activity in skeletal muscle (by 67%). L/A coadministration enhanced insulin sensitivity more than pair-feeding and weight-matched calorie restriction. In conclusion, this study demonstrates the beneficial effect of L/A coadministration on glucose and lipid metabolism in DIO mice, indicating the possible clinical usefulness of L/A coadministration as a new antidiabetic treatment in obesity-associated diabetes.     

Relationship of plasma leptin and adiponectin concentrations with menopausal status in Tunisian women

To evaluate the effect of menopausal status and body mass index (BMI) on circulating leptin and adiponectin concentrations and investigate whether there is an influence of menopausal transition on the relationships of these adipokines and leptin to adiponectin (L/A) ratio with lipid profile and insulin resistance in a sample of Tunisian women. One hundred ninety-six premenopausal (mean age 35.3 ± 7.6 years) and 180 postmenopausal women (mean age 53.4 ± 6.2 years) were included in the study. Participants were stratified into obese and normal weight groups based upon their baseline BMI. Fasting glucose, HDL-cholesterol (HDL-C), triglycerides (TG), total cholesterol (TC), insulin, leptin, and adiponectin concentrations were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Premenopausal women had significantly higher leptin and L/A ratio and lower adiponectin levels than postmenopausal women. Menopause had no effect on the mean values of BMI, insulin or HOMA-IR, HDL-C, and TG. Using a multiple linear regression model, menopausal status was identified, as significant independent predictor for leptin and adiponectin levels. Irrespective of the menopausal status, obese women exhibited higher leptin and L/A ratio and lower adiponectin levels compared to those with normal weight. Comparison between the two menopausal stages in obese and normal weight groups showed that leptin and L/A ratio decreased, while adiponectin increased from pre- to postmenopausal stage only in obese group. The L/A ratio correlated better with lipid profile and HOMA-IR in postmenopausal stage. The present study showed a significant interaction between menopause and BMI on leptin and adiponectin secretion. Menopausal transition affects the relationships of these adipokines with lipids and insulin resistance.