Decline In Leptin Research Articles

The effect of exercise training on osteocalcin, adipocytokines, and insulin resistance: a systematic review and meta-analysis of randomized controlled trials.

Recently, it has been reported that osteocalcin (OC), in particular its undercarboxylated (ucOC) form, is not only a bone remodeling marker but also an active hormone that intercedes glucose metabolism in humans. This study aimed to determine the impact of an exercise intervention on ucOC, adiponectin, leptin, and insulin resistance (measured by HOMA-IR). PubMed, CINAHL, Medline, Google Scholar, and Scopus databases and reference lists of included studies were searched. Twenty-two randomized controlled trials (RCTs) of exercise training impact in adults were included in the analysis. Results showed an overall significant increase in serum ucOC (MD: 0.15ng/ml; 95% CI: 0.05 to 0.25) and adiponectin (MD: 2.83mg/ml; 95% CI: 1.67 to 3.98), a significant decline in leptin (MD: - 4.89pg/ml; 95% CI: - 6.94 to - 2.84), fasting glucose (MD: - 2.29mg/dl; 95% CI: - 4.04 to - 0.54), fasting insulin (MD, - 8.90μIU/ml; 95% CI: - 13.81 to - 3.98), and HOMA-IR (MD: - 1.96; 95% CI: - 3.11 to - 0.80). However, after removal of studies that had prescribed a balanced diet along with exercise intervention, total OC (TOC) levels also increased in the exercise group compared with the control group (MD: 0.36ng/ml; 95% CI: 0.07 to 0.65). Our findings demonstrate that exercise-induced increases in ucOC are the probable cause of increased adiponectin. Additionally, increases in ucOC itself are probably due to changes in leptin levels and other factors, rather than its direct impact on bone and its osteoblastic activity. Further studies are required to clarify the mechanisms underlying the impact of exercise training on ucOC, adipocytokines, and insulin resistance.

Decreased Leptin Is Associated with Alterations in Thyroid-Stimulating Hormone Levels after Roux-en-Y Gastric Bypass Surgery in Obese Euthyroid Patients with Type 2 Diabetes

Background: Leptin has been shown to stimulate the hypothalamus-pituitary-thyroid (HPT) axis in vivo and vitro. Its role in thyroid axis regulation after weight loss induced by bariatric surgery is still unknown. The aim of this study was to evaluate the influence of leptin on weight loss and thyroid function variation induced by Roux-en-Y gastric bypass (RYGB) surgery in euthyroid individuals with obesity and type 2 diabetes mellitus (T2DM). Methods: 65 Chinese individuals with obesity and T2DM who underwent RYGB, and 27 healthy volunteers were enrolled in this retrospective study. Participants were evaluated for changes in anthropometric parameters, metabolic indexes, thyroid function, and leptin levels before and 12 months after surgery. Results: After RYGB, all of these patients experienced significant weight reduction and improved glucose control. Metabolic parameters were significantly ameliorated after surgery compared with baseline. Thyroid hormones including free triiodothyronine (FT₃), free thyroxine (FT₄), and thyroid-stimulating hormone (TSH) declined in parallel. Median (IQR) plasma leptin levels decreased from 33.7 ng/mL (17.9–63.1) to 10.3 ng/mL (4.0–18.5). Pearson correlation analysis showed that TSH was significantly positively correlated with body mass index, C-reactive protein (CRP), and leptin. Multiple stepwise linear regression indicated that leptin and CRP were independent factors affecting TSH. The β coefficients were 0.38 (p = 0.001) and 0.32 (p = 0.004), respectively. There was a significant positive correlation between ΔTSH and Δleptin (r = 0.33, p = 0.01). Conclusion: Decreased or normalized TSH levels after weight loss induced by RYGB might be mediated by the decline in leptin. There could be cross talk between adipose tissue and the HPT axis.

Change of peripheral blood appetite regulation factor of anorexia children and infect of child anorexia granule

Study the infect of child anorexia granule on serum ghrelin and leptin of anorexia children and its clinical efficacy. Selected 81 cases of anorexia children aged 1-6 years old into treatment group (42 cases) and control group (39 cases), in addition, 30 case healthy children as healthy control group. The control group children were treated with domperidone suspension 0.3 mg x kg(-1) x d(-1), tid, orally 30 minutes before meals. Treatment group were treated with child anorexia granule, 1-3 years 1 package, bid; 4-6 years 1 package, tid; po, 4 weeks as a course of treatment. Study the change of serum ghrelin and leptin before and after therapy. The study demonstrates that before treatment, the serum ghrelin level of disease group was lower than healthy group (P < 0.01), and the serum leptin level was higher than healthy group (P < 0.01). After treatment, the serum ghrelin level both increase, and the serum leptin decline. And the change of treatment group was significantly different with control group (P < 0.01). And the clinical effective rate are 95.23% and 74.35% (P < 0.01). After 6 months of follow-up visit, the children weight significantly increase in treatment group (P < 0.01). Results indicate that child anorexia granule can facilitate secretion of ghrelin, and inhibit secretion of leptin, so as to work up an appetite. And the molecular mechanism is its infect on serum ghrelin, leptin.

Randomized double‐blind placebo‐controlled study of leptin administration after gastric bypass

ObjectiveObese individuals have high levels of circulating leptin and are resistant to the weight-reducing effect of leptin administration at physiological doses. Although Roux-en-Y gastric bypass (RYGB) is an effective weight loss procedure, there is a plateau in weight loss and most individuals remain obese. This plateau may be partly due to the decline in leptin resulting in a state of relative leptin insufficiency. The main objective of this study was to determine whether leptin administration to post-RYGB patients would promote further weight reduction.Design and MethodsThis was a randomized, double-blind, placebo-controlled cross-over study of 27 women who were at least 18 months post-RYGB and lost on average 30.8% of their pre-surgical body weight. Subjects received either leptin or placebo via subcutaneous injection twice daily for 16 weeks, then crossed over to receive the alternate treatment for 16 weeks.ResultsWeight change after 16 weeks of placebo was not significantly different from that after 16 weeks of leptin. No changes were observed in percent fat mass, resting energy expenditure, thyroid hormones, or cortisol levels.ConclusionsContrary to our hypothesis, we did not observe a significant effect of leptin treatment on body weight in women with relative hypoleptinemia after RYGB.

Leptin and the Placental Response to Maternal Food Restriction During Early Pregnancy in Mice1

Several studies have demonstrated that maternal undernutrition or overnutrition during pregnancy can have negative consequences for the health of children born to these pregnancies, but the physiological mechanisms by which this occurs are not completely understood. During periods of food restriction, concentrations of leptin decline, whereas leptin is elevated in obesity, suggesting that it may play a role in the response to altered nutrition during pregnancy. This study compares placental development and global placental gene expression profiles at Day 11.5 in pregnant control mice, mice that were undernourished, and mice that were undernourished but given leptin. Placentas from mothers exposed to food restriction preserved the placental labyrinth zone at the expense of the junctional zone, an effect abrogated in the restricted plus leptin group, which had a significant decrease in the labyrinth zone area compared with controls. Similarly, there were more significant differences in gene expression between placentas from control and restricted plus leptin mothers (1128 differentially expressed genes) than between placentas of control and restricted mothers (281 differentially expressed genes). We conclude that the presence of high concentrations of circulating leptin during food restriction disrupts the normal adaptive response of the placenta to reduced energy availability.

Effect of recombinant growth hormone on leptin, adiponectin, resistin, interleukin-6, tumor necrosis factor-α and ghrelin levels in growth hormone-deficient children

Treatment with GH promotes linear growth and decreases body fat in patients with isolated GH deficiency (GHD). However, few studies have analyzed how GH replacement modifies ghrelin levels and the adipokine profile and the relationship of these modifications with the metabolic changes. To analyze the eventual differences between serum levels of leptin, leptin soluble receptor (sOBR), resistin, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), total (TG) and acylated ghrelin (AG) and lipid and glycemic profiles in children with GHD, as well as to determine the effect of GH replacement on these parameters during the first year of therapy. Thirty pre-pubertal (Tanner stage I) GHD children and 30 matched controls were enrolled. Children with GHD were studied before and after 6 and 12 months of GH treatment. Weight, height, BMI, fasting glucose, insulin, lipid profile and serum levels of adipokines and ghrelin were studied at every visit. Adi - pokines, insulin and ghrelin levels were determined by using commercial radio- and enzymoimmunoassays. At baseline children with GHD had significantly higher sOBR (p<0.01) and adiponectin (p<0.01) levels than controls. Treatment with GH resulted in a decline in leptin (p<0.05) and TG (p<0.001) levels, an increase of homeostasis model assessment index and restored IGF-I levels (p<0.001). These data indicate that GH replacement has a negative effect on leptin levels and may also produce a slight unfavorable effect on carbohydrate metabolism. In addition, the changes observed in the adipokine profile appear to be independent of body mass index.

The role of melanocortin neuronal pathways in circadian biology: a new homeostatic output involving melanocortin‐3 receptors?

Obesity, insulin resistance and increased propensity for type 2 diabetes and cardiovascular disease result from an imbalance between energy intake and expenditure. The cloning of genes involved in energy homeostasis produced a simple feedback model for the homeostatic regulation of adipose mass. Serum leptin secreted from adipocytes signals nutrient sufficiency, curbing appetite and supporting energy expenditure. A rapid decline in leptin during nutrient scarcity instigates adaptive mechanisms, including increased appetite and reduced energy expenditure. Hypothalamic melanocortin neurons are important mediators of this response, integrating inputs of energy status from leptin with other peripheral signals. While this feedback response prolongs survival during fasting, other mechanisms allowing the prediction of nutrient availability also confer a selective advantage. This adaptation has been commonly studied in rodents using restricted feeding paradigms constraining food intake to limited periods at 24-h intervals. Restricted feeding rapidly elicits rhythmic bouts of activity and wakefulness anticipating food presentation. While the response exhibits features suggesting a clock-like mechanism, the neuromolecular mechanisms governing expression of food anticipatory behaviours are poorly understood. Here we discuss a model whereby melanocortin neurons regulating the homeostatic adaptation to variable caloric availability also regulate inputs into neural networks governing anticipatory rhythms in wakefulness, activity and metabolism.

Time course and determinants of leptin decline during weight loss in obese boys and girls

To investigate whether changes in leptin concentrations during weight loss can be explained by gender, puberty, baseline adiposity and changes in adiposity, body composition, rate of weight loss, physical activity and insulin concentrations. A longitudinal study with 9 repeated measures during a 12-week weight loss programme. Fifty-three boys and 62 girls (7.9-15.2 years) with body mass index (BMI) standard deviation scores (SDS) of median 2.78 and 2.70, respectively. Height, weight, fat mass percentage assessed by bioimpedance, Tanner stages, testicular size, physical activity scores, blood leptin (ng/ml) and insulin concentrations (pmol/l) were measured at baseline, and except for Tanner stage and testicular size, repeated regularly during the programme. The weight loss was accompanied by a steep decline in leptin concentrations during the first 10-11 days, followed by a less steep decline until day 82. Leptin declined to 39% in boys and 51% in girls of the level that was expected given the relationship at baseline between leptin and BMI SDS, and the BMI SDS changes during weight loss. The biphasic leptin decline was independent of gender, puberty, baseline adiposity or concomitant changes in BMI SDS, fat mass percentage, rate of weight loss, physical activity scores or insulin concentrations. The biphasic leptin decline, which exceeded the level expected, was independent of puberty, baseline adiposity and changes in adiposity, body composition, rate of weight loss, physical activity scores and insulin concentrations. The dissociation of the leptin-weight relationship during weight loss may contribute to the general leptin variability in obese subjects.

Fasting leptin and appetite responses induced by a 4-day 65%-energy-restricted diet

Animal studies show that the leptin decline after acute severe caloric restriction is a peripheral signal to increase food intake. However, most human studies have failed to observe such a relationship. We studied the acute effects of severe caloric restriction on the association between serum leptin concentrations and subjective appetite. A total of 44 healthy adult men (aged: 43 +/- 5 years; BMI: 27.3 +/- 3.2 kg/m(2)). Fasting serum leptin concentrations and self-perceived appetite levels were measured during a 4-day diet containing 36% of the estimated energy requirements. Appetite levels were assessed with a 10-point Likert scale, reflecting hunger, fullness, desire to eat, prospective consumption and total appetite. After the 4-day energy deficit, fasting leptin concentrations decreased by 39.4% (95% CI: -43.6; -34.9%). This decline was associated with an increase in fasting hunger (r = -0.42; P < 0.01), desire to eat (r = -0.39; P < 0.05) and total appetite (r = -0.38; P < 0.05). Furthermore, the association between fasting leptin concentrations and fasting appetite levels became stronger during the energy restriction period (for total appetite: day 0 r = -0.15, P = 0.32; day 2 r = -0.31, P =< 0.05; day 4 r = -0.41, P < 0.01). The acute proportional reduction in fasting leptin after 4-day energy restriction is associated with an increase in self-perceived appetite. Additionally, the inverse association between proportional fasting leptin concentrations and self-perceived appetite response becomes stronger as energy restriction is prolonged. These findings suggest that leptin has an instrumental role in restoring energy balance in humans through the expression of appetite.

Effects of Physiological Leptin Administration on Markers of Inflammation, Platelet Activation, and Platelet Aggregation during Caloric Deprivation

Leptin is a nutritionally regulated adipocyte-derived cytokine. Previous studies in obese patients have demonstrated increased inflammatory markers and increased platelet aggregation in association with leptin. However, the effects of leptin administration on markers of inflammation and platelet aggregation in a human model of undernutrition have not previously been studied. The objective of the study was to investigate markers of inflammation, platelet activation, and platelet aggregation in a model of caloric deprivation and increased leptin sensitivity. This study was a randomized, placebo-controlled study conducted between November 2002 and November 2003. The study was conducted at an inpatient care setting at the General Clinical Research Center. Twenty healthy, young (18-35 yr old), normal-weight (body mass index, 20-26 kg/m2) women were recruited from local advertisements. No subjects withdrew due to adverse effects. The effects of physiological recombinant methionyl human leptin or identical placebo administration were investigated over a 4-d fast. The primary outcome measures for this study were C-reactive protein (CRP) and indices of platelet activity. Leptin administration prevented the fasting-induced decline in leptin (P < 0.05 vs. placebo at each time point). Leptin administration increased CRP (6.3 +/- 2.4 vs. 0.7 +/- 0.3 mg/liter; P = 0.04), circulating P-selectin (11.6 +/- 10.2 vs. -28.9 +/- 15.6 ng/ml; P = 0.04), and induction of platelet aggregation (5.8 +/- 2.6 vs. -2.7 +/- 2.9%, P = 0.04, percent maximum platelet aggregation) relative to placebo administration (change in leptin vs. change in placebo, respectively, for each variable). Leptin tended to increase serum amyloid A [0.1 +/- 0.2 vs. -0.3 +/- 0.1 log10 (ng/ml); P = 0.07], and the changes in serum amyloid A and CRP were highly correlated (r = 0.83; P < 0.0001). No changes in TNFalpha, IL-6, IL-10, plasminogen activator inhibitor-1, haptoglobin, intercellular adhesion molecule, or vascular cell adhesion molecule were seen between the groups. Our data provide evidence that physiological leptin administration stimulates inflammatory and platelet responses in humans during caloric deprivation.

Chronic REM-sleep deprivation of rats elevates metabolic rate and increases UCP1 gene expression in brown adipose tissue

A cluster of unique pathologies progressively develops during chronic total- or rapid eye movement-sleep deprivation (REM-SD) of rats. Two prominent and readily observed symptoms are hyperphagia and decline in body weight. For body weight to be lost despite a severalfold increase in food consumption suggests that SD elevates metabolism as the subject enters a state of negative energy balance. To test the hypothesis that mediation of this hypermetabolism involves increased gene expression of uncoupling protein-1 (UCP1), which dissipates the thermodynamic energy of the mitochondrial proton-motive force as heat instead of ATP formation in brown adipose tissue (BAT), we 1) established the time course and magnitude of change in metabolism by measuring oxygen consumption, 2) estimated change in UCP1 gene expression in BAT by RT-PCR and Western blot, and 3) assayed serum leptin because of its role in regulating energy balance and food intake. REM-SD of male Sprague-Dawley rats was enforced for 20 days with the platform (flowerpot) method, wherein muscle atonia during REM sleep causes contact with surrounding water and awakens it. By day 20, rats more than doubled food consumption while losing approximately 11% of body weight; metabolism rose to 166% of baseline with substantial increases in UCP1 mRNA and immunoreactive UCP1 over controls; serum leptin decreased and remained suppressed. The decline in leptin is consistent with the hyperphagic response, and we conclude that one of the mediators of elevated metabolism during prolonged REM-SD is increased gene expression of UCP1 in BAT.

Leptin responsiveness to energy restriction: genetic variation in the leptin receptor gene.

Serum leptin concentrations are an important afferent signal in energy balance homeostasis. It has been speculated that the leptin responsiveness to energy restriction is affected by the functionality of the leptin receptor. The purpose of this analysis was to explore the effect of polymorphisms in the LEPR gene on the acute decline in leptin after 4 days of 65% energy restriction. Leptin concentrations of the study group (n = 44; all men) declined by 2.3 +/- 1.5 micro g/L [-39.4% (95% confidence interval: -43.6 to -34.9)]. Leptin responses did not statistically differ between noncarriers and carriers of three mutant variants of the polymorphisms: Lys109/Lys109 (-41.4%) vs. Arg109/+ (-37.0%) (p = 0.33); Gln223/Gln223 (-41.5%) vs. Arg223/+ (-37.8%) (p = 0.40); Lys656/Lys656 (-39.5%) vs. Asn656/+ (-39.3%) (p = 0.96). No effect of the assessed polymorphisms in the LEPR gene on the acute decline in leptin after energy restriction was observed. Power calculations are provided for future studies on the leptin responsiveness to energy restriction.

Leptin and insulin responses to a four-day energy-deficient diet in men with different weight history.

To assess the leptin responses to a 4-day energy-restricted diet in men with different weight history; high retrospective weight gain was expected to be associated with a small decline in leptin. Changes in fasting leptin and insulin were measured during a 4-day controlled intervention, in which men with high retrospective weight gain and men who had stable weight consumed 35% of their estimated energy needs. A total of 44 healthy men (age: 31-52 y, BMI: 22.7-39.8 kg/m(2)) were recruited from a cohort study: 22 men who had gained weight (weight change >1 kg/y) and 22 men whose weight had remained stable (weight change +/-0.3 kg/y) between the first (1987-1991) and the second measurement (1993-1997) of the cohort study. The intervention study was carried out in 2001. After intervention, changes in fasting leptin levels were similar for both groups of retrospective weight gain: -2.2 microlU/ml (95% CI: -2.8; -1.7) and -2.4 microlU/ml (95% CI: -3.2; -1.7) respectively (P=0.69). Proportional changes in fasting leptin levels were different: -43.3% (95% CI: -47.8; -38.4) in the participants whose weight had remained stable (n=22) and -35.2% (95% CI: -42.4; -27.1) in those who had gained weight (n=22)(P<0.05). Analyses in a subgroup of men (n=18), in which the contrast in weight history was more pronounced than in the total group, did not show this difference. A higher proportional decrease in insulin levels was seen in men whose weight remained stable than in those who had gained weight: -35.4% (95% CI: -46.9; -21.3) and -12.8% (95% CI: -28.1; 5.7), respectively. The proportional decrease in leptin was positively associated with the proportional decrease in insulin (r=0.52; P<0.05). The decrease in leptin was positively associated with preintervention body weight (r=0.36; P<0.05), BMI (r=0.44; P<0.05), and waist-circumference (r=0.46; P<0.05). Although we found that the 4-day energy restriction had a smaller effect on the decrease in leptin in men with retrospective weight gain, our study does not show convincing evidence that men who gained weight are less leptin responsive to changes in energy balance than those who were weight stable.

Food Fails to Suppress Ghrelin Levels in Obese Humans

Ghrelin is the first circulating hormone shown to stimulate feeding in humans following systemic administration. Food consumption decreases circulating ghrelin concentrations in lean subjects but the effects of feeding have not been studied in the obese. Methods: We investigated the effects of a test meal on plasma ghrelin and leptin concentrations in 13 lean and 10 obese subjects. Results: Fasting ghrelin was significantly higher in lean than in obese subjects (857 pmol/1 vs. 325 pmol/l, (p = 0.002) and fell by 39.5% thirty minutes after eating in the lean group before returning rapidly towards baseline values: (p = 0.003). There was no change in circulating ghrelin in the obese group. Circulating leptin concentration also fell acutely 15 minutes following food intake in lean but not obese subjects (p < 0.0001). Conclusions: Obese subjects do not exhibit the decline in plasma ghrelin and leptin seen after a meal in the lean. The role of the decline in leptin is unclear but given the orexigenic properties of ghrelin, the lack of suppression following a meal obese subjects could lead to increased food consumption and suggest that ghrelin may be involved in the pathophysiology of obesity.

Food fails to suppress ghrelin levels in obese humans.

Ghrelin is the first circulating hormone shown to stimulate feeding in humans following systemic administration. Food consumption decreases circulating ghrelin concentrations in lean subjects but the effects of feeding have not been studied in the obese. We investigated the effects of a test meal on plasma ghrelin and leptin concentrations in 13 lean and 10 obese subjects. Fasting ghrelin was significantly higher in lean than in obese subjects (857 pmol/1 vs. 325 pmol/l, (p = 0.002) and fell by 39.5% thirty minutes after eating in the lean group before returning rapidly towards baseline values: (p = 0.003). There was no change in circulating ghrelin in the obese group. Circulating leptin concentration also fell acutely 15 minutes following food intake in lean but not obese subjects (p < 0.0001). Obese subjects do not exhibit the decline in plasma ghrelin and leptin seen after a meal in the lean. The role of the decline in leptin is unclear but given the orexigenic properties of ghrelin, the lack of suppression following a meal in obese subjects could lead to increased food consumption and suggest that ghrelin may be involved in the pathophysiology of obesity.

The Leptin Defense against Wasting Is Abolished in the IL-2–Deficient Mouse Model of Inflammatory Bowel Disease

Anorexia is a major complication of inflammatory bowel disease (IBD). We postulated that chronic intestinal inflammation with increased proinflammatory cytokines elevates serum leptin concentration, thereby contributing to anorexia. This hypothesis was studied in interleukin-2-deficient (IL-2(-/-)) mice, a model of IBD with elevated proinflammatory cytokine production. IL-2(-/-), wild-type pair-fed and wild-type control male mice (8 wk old) were fed regular laboratory mouse food for 2 wk. The IL-2(-/-) and pair-fed groups consumed less food and lost weight. Serum leptin concentrations in the IL-2(-/-) mice in the fed state were lower than controls, but not different from pair-fed mice, and paradoxically increased in the starved state to levels significantly higher than both starved control and pair-fed groups. This result did not change when serum leptin was adjusted for amount of body fat. These data show abnormal leptin responses in IL-2(-/-) mice with increased leptin concentrations disproportionate to fat mass and prevention of the normal decline in leptin with food restriction.

The role of leptin resistance in the lipid abnormalities of aging.

Leptin resistance has been implicated in the pathogenesis of obesity-related complications involving abnormalities of lipid metabolism that resemble those of old age. To determine whether development of leptin resistance in advancing age might account for such abnormalities, we compared the effects of hyperleptinemia (>40 ng/ml) induced in 2-month-old and 18-month-old lean wild-type (+/+) Zucker diabetic fatty rats by adenovirus gene transfer. The decline in food intake, body weight, and body fat in old rats was only 25%, 50%, and 16%, respectively, of the young rats. Whereas in young rats plasma free fatty acids fell 44% and triacylglycerol (TG) 94%, neither changed in the rats. In hyperleptinemic young rats, adipocyte expression of preadipocyte factor 1 increased dramatically and leptin mRNA virtually disappeared; there was increased expression of acyl CoA oxidase, carnitine palmitoyl transferase 1, and their transcription factor peroxisome proliferator-activated receptor alpha, accounting for the reduction in body fat. These hyperleptinemia-induced changes were profoundly reduced in the old rats. On a high-fat diet, old rats consumed 28% more calories than the young and gained 1.5x as much fat, despite greater endogenous hyperleptinemia. Expression of a candidate leptin resistance factor, suppressor of cytokine signaling 3 (SOCS-3), was compared in the hypothalamus and white adipocytes of young and old rats before and after induction of hyperleptinemia; hypothalamic SOCS-3 mRNA was approximately 3x higher in old rats before, whereas it was 3x higher in WAT after, hyperleptinemia. We conclude that the anorexic and antilipopenic actions of leptin decline with age, possibly through increased SOCS-3 expression, and that this could account for the associated abnormalities in lipid metabolism of the elderly.

A Low Serum Leptin Level at Baseline and a Large Early Decline in Leptin Predict a Large 1-Year Weight Reduction in Energy-Restricted Obese Humans

A Low Serum Leptin Level at Baseline and a Large Early Decline in Leptin Predict a Large 1-Year Weight Reduction in Energy-Restricted Obese Humans

A Low Serum Leptin Level at Baseline and a Large Early Decline in Leptin Predict a Large 1-Year Weight Reduction in Energy-Restricted Obese Humans1

The difficulty in maintaining weight loss during obesity treatment may be caused by a counteracting neuroendocrine response. It has been proposed that leptin could be a regulator of this response. We examined the relations between leptin levels during an initial very low calorie diet, other simultaneous endocrine changes, and the 1-yr weight reduction. Sixty-nine obese (24 men and 45 women) were treated with very low calorie diet for 16 weeks, followed by a hypocaloric diet for 32 weeks. Serum levels of leptin, insulin, cortisol, and thyroid hormones were measured at weeks 0, 8, and 18. The relative weight reductions after 18 and 48 weeks were 20.1% and 14.4% in men and 15.4% and 11.8% in women. Low initial leptin levels and large declines in serum leptin were associated with a large 1-yr weight loss in both genders. Leptin levels (baseline or changes) were not independently associated with the changes in insulin, cortisol, or thyroid hormones. Our results may indicate that leptin by itself could be of minor importance for the neuroendocrine response to severe caloric restriction in humans.

Serum leptin levels in males with delayed puberty during short-term pulsatile GnRH administration.

Leptin may be a possible trigger for puberty. In normal males, it has been shown that leptin increases from the pre-pubertal to the early pubertal stage, and then declines in the late pubertal stage. We examined leptin levels in six male adolescents (mean age 16.3+/-0.6 yr; range 14.2-17.6 yr) with delayed puberty (constitutional delay of puberty no.=2; idiopathic hypogonadotropic hypogonadism no.=4) during 120 days of subcutaneous pulsatile GnRH administration. A group of subjects in pre-puberty (no.=11), early-puberty (n=10) and mid-puberty (no.=7) were evaluated as controls. Morning blood samples were taken for determination of leptin, testosterone, LH and FSH levels. In delayed puberty subjects blood samples were taken every 30 days after the start of GnRH administration. At each examination BMI and testicular volume were evaluated. A follow-up examination was performed in the 6 patients 1.3-7.5 yr after the end of the 120 days of GnRH therapy. At baseline evaluation in delayed puberty mean leptin levels were 11.3+/-2.0 microg/l (median 11.3 microg/l; range 4.7-17.3 microg/l) and were higher than those found in pre-puberty (p=0.04) and mid-puberty (p=0.001). During GnRH administration there was no change in BMI and leptin levels but there was an increase in gonadotrophin levels, testosterone and testicular volume. One hundred and twenty days after, mean serum leptin were 10.1+/-2.1 microg/l (median 9.1 microg/l; range 3.4-16.8 microg/l). At the end of the study, leptin levels were higher in delayed puberty than in mid-puberty (p=0.002). At the follow-up examination leptin levels were 4.3+/-1.3 microg/l (median 3.4 microg/l; range 1.4-9.1 microg/l) (p=0.03 vs end of 120 days GnRH therapy) while testosterone and BMI were not changed. In conclusion 120-day pulsatile GnRH administration induced in males with delayed puberty physiological-like pubertal changes but not the decline in leptin levels reported during the progression of puberty. Therefore, in males with delayed puberty an impairment in the phenomenon of leptin decline associated with progression of puberty could be suggested. However after retrospective diagnosis of pubertal delay and long-term therapy in subjects with idiopathic hypogonadotropic hypogonadism leptin levels declined. These data seem to indicate that time more than increase in testosterone levels and testicular volume is the determinant of leptin decline at puberty.