Fasting Leptin Concentrations Research Articles

FRI006 Appetite And Food Intake-regulating Hormones In Patients With Craniopharyngioma

Abstract Disclosure: C.S. Martins: None. M.C. Nogueira: None. A. Bueno: None. A.S. Berbel-Júnior: None. A.C. Moreira: None. S.R. Antonini: None. M. De Castro: None. Purpose: In patients with adamantinomatous craniopharyngiomas (aCP), hypothalamic obesity may occur due to hypothalamic involvement by the tumor or therapeutic interventions. Studies on appetite sensations and modulation of orexigenic and anorexigenic hormones may contribute to understand the pathogenesis of obesity in aCP patients. Patients and Methods: Fifteen patients (9F, 6M; 31.1±12.0 years) presenting aCP submitted to surgical resection and 15 controls paired by sex, age (31±11.7 years) and Body Mass Index (BMI) were evaluated. Leptin and adiponectin were measured in basal conditions, whereas glucose, insulin, GLP-1, PYY and ghrelin levels were assessed in basal conditions and 30, 60, 120 and 180 minutes after a standard meal test consisted by 70 g of hyposodic soy protein isolate-based powder diluted in 250 mL water to be consumed in up to 10 minutes, resulting in a drink of 315 Kcal with 44.1 g carbohydrate, 10.5 g fat, and 11.0 g protein (56%, 30%, and 14% of total calories, respectively). At the same time points, sensations of hunger, fullness and prospective food consumption were measured by a Visual Analogic Scale (VAS) composed of horizontal lines. Individuals were asked to mark across the line the point correspondent to their sensations, and the distance to the left end of the line was quantified. The term “hunger” was evaluated by the question “How much hunger do you feel?” The answers at the VAS were “I’m not hungry at all” and “I’ve never been so hungry.” The feeling of fullness was evaluated by the question “How satisfied are you?” and the answers were “I am completely empty” and “I am completely full.” Prospective consumption was evaluated by the question “How much do you think you can eat?” and the answers were “nothing” and “too much”. Results: Patients’ BMI were 30.9 ± 7.6 kg/m2. In aCP patients, differently from controls, the decrease of hunger from baseline to 60 minutes after the meal was not observed, demonstrating a more transient reduction in the sensation of hunger. In addition, a decrease of fullness sensation from 30 to 120 minutes (p=0.03) was observed, demonstrating a less durable sensation of fullness. There was a tendency towards higher fasting leptin concentrations in patients with aCP (p=0.06), while adiponectin levels were lower in patients (p=0.002). Insulin (p=0.01) and HOMA-IR (p=0.001) were higher in aCP patients compared to controls at 3 hours after meal, whereas GLP-1 (P=0.03) and PYY (p=0.02) were higher at 2 hours after the meal. PYY and ghrelin showed earlier postprandial rise and fall, respectively, in aCP patients. Conclusions: After the test, aCP patients exhibited more transient reduction in the sensation of hunger and less durable sensation of fullness than controls. Changes in appetite sensations and unregulated secretion of orexigenic and anorexigenic hormones may contribute to increased food intake and to the pathogenesis of obesity in aCP patients. Presentation: Friday, June 16, 2023

Bariatric surgery restores visual cortical plasticity in nondiabetic subjects with obesity.

Obesity leads to changes in synaptic plasticity. We aimed at investigating the impact of bariatric surgery (RYGB) on visual neural plasticity (NP) and its relationship with the main gut peptides, leptin, and brain-derived neurotrophic factor (BDNF). NP was assessed testing binocular rivalry before and after 2 h of monocular deprivation (index of visual brain plasticity) in 15 subjects with obesity (age 42.3 ± 9.8 years; BMI 46.1 ± 4.9 kg/m2) before and after RYGB. Gut peptides, leptin, and BDNF were obtained at baseline and 6 months after surgery in 13 subjects. A significant reduction in BMI (p < 0.001 vs. baseline) and a significant increase of disposition index (DI, p = 0.02 vs baseline) were observed after RYGB. Total and active GLP-1 release in response to glucose ingestion significantly increased after RYGB, while no changes occurred in VIP, GIP, and BDNF levels. Fasting leptin concentration was lower after RYGB (p = 0.001 vs. baseline). Following RYGB, NP was progressively restored (p < 0.002). NP was correlated with DI and fasting glucose at baseline (r = 0.75, p = 0.01; r = -0.7, p = 0.02; respectively), but not with BMI. A positive correlation between post-pre-RYGB changes in AUCactive GLP-1 and NP was observed (r = 0.70, p < 0.01). Leptin was inversely correlated with NP 6 months after surgery (r = -0.63, p = 0.02). No correlation was observed between GIP, VIP, BDNF, and NP. Visual plasticity is altered in subjects with obesity, and it can be restored after RYGB. The improvement may be mediated by amelioration of insulin sensitivity, increased GLP-1 levels, and reduced leptin levels.

Appetite Control across the Lifecourse: The Acute Impact of Breakfast Drink Quantity and Protein Content. The Full4Health Project.

Understanding the mechanisms of hunger, satiety and how nutrients affect appetite control is important for successful weight management across the lifecourse. The primary aim of this study was to describe acute appetite control across the lifecourse, comparing age groups (children, adolescents, adults, elderly), weight categories, genders and European sites (Scotland and Greece). Participants (n = 391) consumed four test drinks, varying in composition (15% (normal protein, NP) and 30% (high protein, HP) of energy from protein) and quantity (based on 100% basal metabolic rate (BMR) and 140% BMR), on four separate days in a double-blind randomized controlled study. Ad libitum energy intake (EI), subjective appetite and biomarkers of appetite and metabolism (adults and elderly only) were measured. The adults’ appetite was significantly greater than that of the elderly across all drink types (p < 0.004) and in response to drink quantities (p < 0.001). There were no significant differences in EI between age groups, weight categories, genders or sites. Concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were significantly greater in the elderly than the adults (p < 0.001). Ghrelin and fasting leptin concentrations differed significantly between weight categories, genders and sites (p < 0.05), while GLP-1 and PYY concentrations differed significantly between genders only (p < 0.05). Compared to NP drinks, HP drinks significantly increased postprandial GLP-1 and PYY (p < 0.001). Advanced age was concomitant with reduced appetite and elevated anorectic hormone release, which may contribute to the development of malnutrition. In addition, appetite hormone concentrations differed between weight categories, genders and geographical locations.

The Influence Of Heat On Appetite Regulating Hormones

Leptin has been established as an energy-controlling hormone because of its role in activating the JAK-STAT3 pathway. Temperature has its own prominent role governing appetite regulation and thus, energy expenditure. Previous research has demonstrated consistent decreases in leptin while in a fasted state. Exercising in the heat (1-hour of cycling @60% VO2max in 33°C) has also shown reductions in leptin. However, in order to elucidate the influence of environment, independent of exercise, a fasted resting investigation is needed. PURPOSE: Determine the impact of environmental temperature (33 vs. 20°C) on adipose derived appetite-regulating hormones (leptin and adiponectin) and the impact on energy expenditure. METHODS: 10 college-aged males (27.3 ± 5 y, 86.7 ± 13 kg, and 1.83 ± 4.3 m; 25.8 ± 0.9 kg/m2) completed two randomized, resting experimental trials in the Heat (HT, 33°C) and at Room Temperature (RT, 20°C) at 60% humidity. Blood draws were taken before intervention and after 3 hours for analysis of leptin and adiponectin. Oxygen consumption was measured at 1-, 2-, and 3-hr time-points. RESULTS: HT trial temperatures were greater than RT for both core (mean ± SEM; 37.17 ± 0.08 vs. 36.89 ± 0.08°C, p = 0.002) and skin (37.59 ± 0.10 vs. 32.65 ± 0.48°C; p < 0.001). Oxygen consumption in HT was greater than RT during the 2nd (4.37 ± 0.14 vs. 4.13 ± 0.15 ml/kg/min, p = 0.037) and 3rd hours (4.95 ± 0.26 vs. 4.28 ± 0.19 ml/kg/min, p = 0.002). Fasting leptin concentrations in RT decreased to a greater extent than in HT (mean Δ ± 95% CI; -2.05 ± 1.72 vs. -0.89 ± 1.67 ng/ml; p = 0.036, respectively); however, after adjustment for plasma volume shifts (-7.5%) the interactive effect dissipated (-1.79 ± 1.72 vs. -0.89 ± 1.6 ng/ml; p = 0.068). CONCLUSIONS: The addition of heat stress increased energy expenditure and attenuated the leptin reduction. These data may have implications for appetite control and weight management.

Exercise improves adiposopathy, insulin sensitivity and metabolic syndrome severity independent of intensity.

What is the central question of this study? What are the effects of work-matched continuous versus high-intensity interval training for 2weeks on adiposopathy and cardiometabolic risk in obese adults with prediabetes? What is the main finding and its importance? Independent of intensity, short-term exercise improves adiposopathy and insulin sensitivity. While both exercise intensities reduced fasting leptin concentrations and metabolic syndrome severity, only interval training elevated total adiponectin. In contrast to previous work, neither condition altered high-molecular weight adiponectin. Collectively, these data suggest that short-term exercise can improve adipokine profiles, which may aid in reducing cardiometabolic risk prior to clinically meaningful weight loss in adults with prediabetes. Individuals with prediabetes who are overweight and obese are at an increased risk of developing endocrine disruption of fat tissue, known as adiposopathy. While short-term exercise improves adipokine profiles, the effects of exercise intensity when matched for energy expenditure on adiposopathy are unknown. We hypothesized that high-intensity exercise would elicit greater changes in adiposopathy compared to moderate exercise. Twenty-eight overweight and obese adults (age: 60.9±8.4years; BMI: 33.0±5.4kgm-2 ) with prediabetes were randomized to twelve 60-min sessions of either moderate-continuous (CONT; n=14) or high-intensity interval (INT; n=14) exercise training. Total and high molecular weight (HMW) adiponectin and leptin were collected to assess adiposopathy (ratio of total adiponectin to leptin; A/L). Insulin sensitivity (SIIS ) was determined using a 75goral glucose tolerance test before and after training. Cardiometabolic risk factors were measured and a z-score was calculated to determine metabolic syndrome (MetS) severity. CONT and INT increased A/L (P<0.01) and decreased leptin (P<0.01) and MetS severity (P=0.04). Neither intervention altered circulating levels of HMW adiponectin (P=0.76) and only INT increased total adiponectin levels (P=0.02). Both intensities increased insulin sensitivity (P<0.01), which was associated with improvements in A/L (r=0.47, P=0.01). Additionally, increases in A/L tended to relate to decreased MetS severity (r=-0.36, P=0.09). Short-term exercise intensity, when matched for energy expenditure, does not differentially affect improvements in adiposopathy in overweight and obese adults with prediabetes. Further, 12 bouts of exercise improved insulin sensitivity and MetS severity, suggesting that improving adipokine profiles may aid in reducing cardiometabolic risk.

Influence of sleep restriction on weight loss outcomes associated with caloric restriction.

To examine the effects of moderate sleep restriction (SR) on body weight, body composition, and metabolic variables in individuals undergoing caloric restriction (CR). Overweight or obese adults were randomized to an 8 week caloric restriction (CR) regimen alone (n = 15) or combined with sleep restriction (CR + SR) (n = 21). All participants were instructed to restrict daily calorie intake to 95 per cent of their measured resting metabolic rate. Participants in the CR + SR group were also instructed to reduce time in bed on five nights and to sleep ad libitum on the other two nights each week. The CR + SR group reduced sleep by 57 ± 36 min per day during SR days and increased sleep by 59 ± 38 min per day during ad libitum sleep days, resulting in a sleep reduction of 169 ± 75 min per week. The CR and CR + SR groups lost similar amounts of weight, lean mass, and fat mass. However, the proportion of total mass lost as fat was significantly greater (p = 0.016) in the CR group. This proportion was greater than body fat percentage at baseline for the CR (p = 0.0035), but not the CR + SR group. Resting respiratory quotient was reduced (p = 0.033) only in CR, and fasting leptin concentration was reduced only in CR + SR (p = 0.029). Approximately 1 hr of SR on five nights a week led to less proportion of fat mass loss in individuals undergoing hypocaloric weight loss, despite similar weight loss. SR may adversely affect changes in body composition and "catch-up" sleep may not completely reverse it. ClinicalTrials.gov (NCT02413866).

Metabolomics reveals an entanglement of fasting leptin concentrations with fatty acid oxidation and gluconeogenesis in healthy children.

BackgroundLeptin and adiponectin communicate with organ systems in order to regulate energetic and metabolic homeostasis. Their different points of action have been well characterized; however, no study has investigated their interrelationship with the metabolism at the molecular level in vivo.ObjectiveTo examine the associations of leptin and adiponectin with the metabolic profile reflecting the intercellular and interorgan communication as well as activated metabolic pathways.Patients/MethodsWe measured plasma concentrations of leptin, adiponectin, and insulin along with concentrations of 196 metabolites in 400 healthy, fasting 8-years old German children who participated in the German Ulm Birth Cohort Study (UBCS). Using multiple linear mixed models, we evaluated the associations between hormones and metabolites.ResultsLeptin levels increased exponentially with increasing BMI. Leptin was furthermore strongly associated with alanine and aspartate (Bonferroni corrected P[PBF] = 5.7×10−8 and 1.7×10−6, respectively), and negatively associated to the sum of the non-esterified fatty acids (NEFA) and the sum of the long-chain acylcarnitines C12–C18 (PBF = 0.009 and 0.0001, respectively). Insulin showed a similar association pattern, although the associations were less strong than for leptin. Adiponectin was neither related to BMI nor to any metabolite.ConclusionAlthough children were presumably metabolically similar, we found strong associations of insulin and leptin with the metabolite profile. High alanine concentrations and the lower concentrations of NEFA in children with high fasting leptin concentrations might arise from an increased gluconeogenesis and from the disinhibiting effect of leptin on the carnitine-palmitoyltransferase-1, respectively. As insulin had the same trend towards these associations, both hormones seem to be related to processes that provide the body with energy in fasting state.

The ghrelin and leptin responses to short-term starvation vs a carbohydrate-free diet in men with type 2 diabetes; a controlled, cross-over design study.

BackgroundWe recently have reported the 24-hour glucose, insulin and glucagon responses to a 72-hour fast compared to a 72-hour macronutrient-sufficient, carbohydrate-free diet in men with type 2 diabetes. The 72-hour time period was used because it is the time required for the major metabolic adjustments to a lack of food to be instituted. As part of that study, ghrelin and leptin responses were monitored.MethodsTwenty-four-hour total ghrelin and overnight fasting leptin concentrations were determined in males with type 2 diabetes when ingesting a standard, mixed meal diet (control), followed by a carbohydrate-free diet for 72 h or were starved for 72 h, using a crossover design.ResultsA rise in ghrelin concentration before and a decrease after meals was present when the standard diet was ingested. However, in contrast to literature reports in normal subjects, a circadian variation was not apparent. Meal related changes were absent with starvation. A carbohydrate-free diet resulted in a daylong decrease in ghrelin. It also resulted in a 19 % decrease in the overnight fasting leptin concentration. Leptin was decreased 54 % with total starvation.ConclusionIngestion of a typical mixed-meal diet results in meal-related changes in ghrelin similar to those reported in normal subjects, although the circadian rhythm was not apparent. Except for the lack of meal-related changes, starvation did not change the concentration. A carbohydrate-free, high fat diet resulted in a daylong suppression of ghrelin. The leptin concentration was decreased by both the carbohydrate-free diet and starvation.Trial registrationClinicalTrials.gov Identifier: NCT01469104.

Altered Appetite-Mediating Hormone Concentrations Precede Compensatory Overeating After Severe, Short-Term Energy Deprivation in Healthy Adults

Background: Adaptive responses of appetite-mediating hormones to negative energy balance are thought to contribute to a counterregulatory response that drives weight regain, but they have not been studied while controlling for reduced diet volume.Objective: In this secondary analysis, we aimed to determine the effects of short-term, severe energy deprivation (ED) on appetite and appetite-mediating hormone concentrations.Methods: Twenty-one adults with a mean ± SD age of 21 ± 3 y and body mass index of 25 ± 3 kg/m2 consumed isovolumetric diets provided over separate 48-h periods while increasing habitual energy expenditure by 1683 ± 329 kcal/d through light- and moderate-intensity exercise. Energy intake was matched to energy expenditure to maintain energy balance (EB) (−44 ± 92 kcal/d) or was <10% of energy expenditure to generate a −3696 ± 742-kcal/d energy deficit. Postprandial appetite, glucose, insulin, acyl ghrelin, peptide YY, pancreatic polypeptide (PP), and glucagon-like peptide-1 (GLP-1) responses and ad libitum energy intake were measured as secondary outcomes after both experimental periods.Results: Fasting insulin (−56% ± 42%) and acyl ghrelin (−60% ± 17%) concentrations decreased during ED but not during EB (condition-by-time interaction; P-interaction ≤ 0.01), whereas fasting leptin concentrations decreased more during ED compared with during EB (−47% ± 27% compared with −20% ± 27%; P-interaction = 0.05). Postprandial insulin (57% ± 63%; P < 0.001), GLP-1 (14% ± 28%; P = 0.04), and PP (54% ± 52%; P < 0.001) areas under the curve (AUCs) were higher, whereas the acyl ghrelin AUC was lower (−56% ± 13%; P < 0.001) after ED compared with after EB. After ED, self-rated appetite was greater, and ad libitum energy intake was 811 kcal/36 h (95% CI: 184, 1439 kcal/36 h) higher relative to after EB (P = 0.01).Conclusions: Short-term, severe ED suppressed acyl ghrelin concentrations and increased postprandial anorexigenic hormone concentrations. These effects preceded compensatory overeating, suggesting that in adults without obesity, altered sensitivity to appetite-mediating hormones may contribute to an adaptive counterregulatory response during the initial stages of negative EB. This trial was registered at clinicaltrials.gov as NCT01603550.

Impact of Duodenal-Jejunal Exclusion on Satiety Hormones.

Bariatric procedures that exclude the proximal small intestine lead to significant weight loss which is probably mediated by changes in hormones that alter appetite, such as peptide YY (PYY), ghrelin, cholecystokinin (CCK), and leptin. Here, the effect of the non-surgical duodenal-jejunal bypass liner (DJBL) on concentrations of hormones implicated in appetite control was investigated. A two-center prospective study was conducted between January and December 2010. Seventeen obese subjects with type 2 diabetes were treated with the DJBL for 24 weeks. Fasting concentrations of leptin and meal responses of plasma PYY, CCK, and ghrelin were determined prior to and after implantation of the DJBL. At baseline, subjects had an average body weight of 116.0 ± 5.8 kg. One week after implantation, subjects had lost 4.3 ± 0.6 kg (p < 0.01), which progressed to 12.7 ± 1.3 kg at week 24 (p < 0.01). Postprandial concentrations of PYY and ghrelin increased (baseline vs. week 1 vs. week 24 PYY: 2.6 ± 0.2 vs. 4.1 ± 0.4 vs. 4.1 ± 0.7 nmol/L/min and ghrelin: 7.8 ± 1.8 vs. 11.0 ± 1.8 vs. 10.6 ± 1.8 ng/mL/min, all p < 0.05). In parallel, the CCK response decreased (baseline vs. week 1 vs. week 24: 434 ± 51 vs. 229 ± 52 vs. 256 ± 51 pmol/L/min, p < 0.01). Fasting leptin concentrations also decreased (baseline vs. week 24: 98 ± 17 vs. 53 ± 10 ng/mL, p < 0.01). DJBL treatment induces weight loss paralleled by changes in concentrations of hormones involved in appetite control.

Metabolic determinants of body weight after cats were fed a low-carbohydrate high-protein diet or a high-carbohydrate low-protein diet ad libitum for 8 wk

Overweight and obese conditions are common in cats and are associated with the development of a number of diseases. Knowledge of metabolic determinants and predictors of weight gain may enable better preventative strategies for obesity in cats. Lean, healthy cats were fed either a low-carbohydrate high-protein diet (n 16) or a high-carbohydrate low-protein (n 16) diet ad libitum for 8 wk. Potential determinants and predictors of final body weight assessed were body fat and lean masses, energy required for maintenance, energy requirements above maintenance for each kilogram of weight gain, insulin sensitivity index, fasting, mean 24-h and peak plasma glucose, insulin, and leptin concentrations, and fasting and mean 24-h serum adiponectin concentrations. In cats fed the low-carbohydrate high-protein diet, after adjusting for initial body weight, those with higher energy requirements for weight gain and higher fasting glucose concentration had higher final body weights (P ≤ 0.01). Predicted final body weights using initial body weight, fasting glucose and mean 24-h insulin concentrations (partial R2 37.3%) were imprecise. An equation using just initial body weight and fasting glucose concentration would be of more practical value, but was marginally less precise. In cats fed the high-carbohydrate low-protein diet, those with lower fasting leptin concentration initially had higher final body weights (P = 0.01). Predicted final body weights using initial body weight, energy requirements for maintenance, total body fat percentage and fasting leptin concentration (partial R2 39.2%) were reasonably precise. Further studies are warranted to confirm these findings and to improve the precision of predicted final body weights.

Long-lived crowded-litter mice exhibit lasting effects on insulin sensitivity and energy homeostasis.

The action of nutrients on early postnatal growth can influence mammalian aging and longevity. Recent work has demonstrated that limiting nutrient availability in the first 3 wk of life [by increasing the number of pups in the crowded-litter (CL) model] leads to extension of mean and maximal lifespan in genetically normal mice. In this study, we aimed to characterize the impact of early-life nutrient intervention on glucose metabolism and energy homeostasis in CL mice. In our study, we used mice from litters supplemented to 12 or 15 pups and compared those to control litters limited to eight pups. At weaning and then throughout adult life, CL mice are significantly leaner and consume more oxygen relative to control mice. At 6 mo of age, CL mice had low fasting leptin concentrations, and low-dose leptin injections reduced body weight and food intake more in CL female mice than in controls. At 22 mo, CL female mice also have smaller adipocytes compared with controls. Glucose and insulin tolerance tests show an increase in insulin sensitivity in 6 mo old CL male mice, and females become more insulin sensitive later in life. Furthermore, β-cell mass was significantly reduced in the CL male mice and was associated with reduction in β-cell proliferation rate in these mice. Together, these data show that early-life nutrient intervention has a significant lifelong effect on metabolic characteristics that may contribute to the increased lifespan of CL mice.

Hormonal responses and test meal intake among obese teenagers before and after laparoscopic adjustable gastric banding

Relatively little is known about changes in eating behavior or hormonal responses to food after bariatric surgery in adolescents. This study compared eating behavior and hormones among adolescents in a bariatric surgery program with those in nonoverweight control adolescents and evaluated changes before and after laparoscopic adjustable gastric banding (LAGB). Fasting leptin, peptide YY (PYY), and ghrelin concentrations were obtained, and postprandial ghrelin and PYY area under the curve (AUC) were assessed after a single-item breakfast. Intake from an ad libitum lunchtime multi-item meal was measured. Compared with controls (n = 9), all presurgical candidates (n = 20) had significantly greater fasting leptin, lower fasting ghrelin, and lower AUC ghrelin but similar PYY and AUC PYY. Preoperative candidates did not differ from controls in total energy consumed during the test meal. Postoperatively, among the 11 participants with data both before and after surgery, BMI (in kg/m(2)) decreased by 3.5 (P < 0.001), significantly less energy was consumed in the test meal, and a smaller number of foods were selected. AUC ghrelin and PYY did not significantly change before or after LAGB. Few significant short-term changes were observed in appetitive hormones after LAGB. It is unclear whether objective measures of eating behavior will prove useful in evaluating the impact of bariatric surgery on outcomes. This trial was registered at clinicaltrials.gov as CT00764127.

Effects of sugar‐sweetened beverages on plasma acylation stimulating protein, leptin and adiponectin: Relationships with Metabolic Outcomes

ObjectiveWe determined the effects of fructose and glucose consumption on plasma acylation stimulating protein (ASP), adiponectin, and leptin concentrations relative to energy intake, body weight, adiposity, circulating triglycerides, and insulin sensitivity.Design and Methods32 overweight/obese adults consumed glucose- or fructose-sweetened beverages (25% energy requirement) with their ad libitum diets for 8 weeks, followed by sweetened beverage consumption for 2 weeks with a standardized, energy-balanced diet. Plasma variables were measured at baseline, 2, 8 and 10 weeks, and body adiposity and insulin sensitivity at baseline and 10 weeks.ResultsFasting and postprandial ASP concentrations increased at 2 and/or 8 weeks. ASP increases correlated with changes in late-evening triglyceride concentrations. At 10 weeks, fasting adiponectin levels decreased in both groups, and decreases were inversely associated with baseline intra-abdominal fat volume. Sugar consumption increased fasting leptin concentrations; increases were associated with body weight changes. 24-h leptin profiles increased during glucose consumption and decreased during fructose consumption. These changes correlated with changes of 24-h insulin levels.ConclusionsThe consumption of fructose and glucose beverages induced changes in plasma concentrations of ASP, adiponectin and leptin. Further study is required to determine if these changes contribute to the metabolic dysfunction observed during fructose consumption.

Common Genetic Variation in the SERPINF1 Locus Determines Overall Adiposity, Obesity-Related Insulin Resistance, and Circulating Leptin Levels

ObjectivePigment epithelium-derived factor (PEDF) belongs to the serpin family of peptidase inhibitors (serpin F1) and is among the most abundant glycoproteins secreted by adipocytes. In vitro and mouse in vivo data revealed PEDF as a candidate mediator of obesity-induced insulin resistance. Therefore, we assessed whether common genetic variation within the SERPINF1 locus contributes to adipose tissue-related prediabetic phenotypes in humans.Subjects/MethodsA population of 1,974 White European individuals at increased risk for type 2 diabetes was characterized by an oral glucose tolerance test with glucose and insulin measurements (1,409 leptin measurements) and genotyped for five tagging SNPs covering 100% of common genetic variation (minor allele frequency ≥0.05) in the SERPINF1 locus. In addition, a subgroup of 486 subjects underwent a hyperinsulinaemic-euglycaemic clamp and a subgroup of 340 magnetic resonance imaging (MRI) and spectroscopy (MRS).ResultsAfter adjustment for gender and age and Bonferroni correction for the number of SNPs tested, SNP rs12603825 revealed significant association with MRI-derived total adipose tissue mass (p = 0.0094) and fasting leptin concentrations (p = 0.0035) as well as nominal associations with bioelectrical impedance-derived percentage of body fat (p = 0.0182) and clamp-derived insulin sensitivity (p = 0.0251). The association with insulin sensitivity was completely abolished by additional adjustment for body fat (p = 0.8). Moreover, the fat mass-increasing allele of SNP rs12603825 was significantly associated with elevated fasting PEDF concentrations (p = 0.0436), and the PEDF levels were robustly and positively associated with all body fat parameters measured and with fasting leptin concentrations (p<0.0001, all).ConclusionIn humans at increased risk for type 2 diabetes, a functional common genetic variant in the gene locus encoding PEDF contributes to overall body adiposity, obesity-related insulin resistance, and circulating leptin levels.

Physical Activity, Fitness, and Serum Leptin Concentrations in Adolescents

To examine the association of physical activity and fitness with leptin concentrations in European adolescents, after taking into account several potential confounders including total body fat (TBF). We conducted a cross-sectional study in a school setting for the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. This study included 902 (509 girls) adolescents aged 12.5-17.5 years. Weight, height, and TBF (sum of 6 skinfold thickness) were measured, and fat free mass and body mass index were calculated. Physical activity was assessed by accelerometry. Physical fitness was assessed by the handgrip, standing long jump, 4 × 10-m shuttle run, and 20-m shuttle run tests. Serum fasting leptin, insulin, and glucose concentrations were measured, and homeostasis model assessment was computed. Multiple linear regression models were used. Vigorous physical activity and fitness tests (all P < .05) were negatively associated with leptin, independently of several confounders including TBF and homeostasis model assessment. These associations remained significant after further controlling for each other (physical activity and fitness). These results suggest that vigorous physical activity and fitness moderate the levels of leptin concentrations, regardless of relevant confounders including TBF. Intervention programs addressed to increase high intensity physical activity and fitness as well as to assess its impact on leptin concentration are required.

Hyperleptinemia positively correlated with metabolic syndrome in renal transplant recipients

Our aim was to evaluate the relationship between metabolic syndrome and fasting serum leptin concentration in renal transplant recipients. Fasting blood samples were obtained from 55 renal transplant recipients. Metabolic syndrome and its components were defined using the diagnostic criteria of the International Diabetes Federation. Thirteen patients (23.6%) had metabolic syndrome. Fasting leptin concentrations were positively correlated with metabolic syndrome (p=0.003). Univariate linear regression analysis indicated fasting serum leptin values were positively correlated with waist circumference (r=0.284; p=0.036), body mass index (r=0.358; p=0.007), body fat mass (r=0.610; p<0.001), triglycerides (r=0.268; p=0.048), high-sensitivity C-reactive protein (hs-CRP) (r=0.377; p=0.005), triceps skinfold (r=0.335; p=0.012), and mid-arm fat area (r=0.351; p=0.009). Multivariate forward stepwise linear regression analysis of the significant variables revealed that body fat mass (R2 change=0.373; p<0.001) and hs-CRP (R2 change=0.045; p=0.049) were the independent predictors of fasting serum leptin concentration. Serum leptin concentration correlates positively with metabolic syndrome in renal transplant recipients.

PLASMA LEPTIN CONCENTRATION, INSULIN RESISTANCE, CLINICAL AND BIOCHEMICAL PARAMETERS IN PATIENTS PRESENTING ESSENTIAL HYPERTENSION WITH OR WITHOUT METABOLIC SYNDROME: PP.34.435

Objective: Leptin is one of the cytokines secreted by adipocytes and plays an important role in the regulation of food intake, energy expenditure, insulin secretion and activation of sympathetic tone. The aim of the study was to estimate the relationship between plasma leptin concentration, insulin resistance, sympathetic nervous system activity, blood pressure values and metabolic parameters in patients presenting essential hypertension with or without metabolic syndrome. Design and Methods: The study group consisted of 53 patients divided into 2 subgroups:1. subjects with metabolic syndrome and hypertension (n = 31), 2. subjects with essential hypertension, without obesity (n = 22). The control group included 15 normotensive, non-obese individuals in comparable age (group nr 3). In all subjects fasting leptin concentration was measured using RIA test. Fasting and postprandial glucose and insulin levels, lipid profile, systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), BMI, waist circumference and adipose tissue mass – were also assessed. Mean insulin resistance ratio (IR) was calculated by quotient of fasting insulin and glucose concentrations. Results: Mean plasma leptin concentrations (±SD) in 3 groups were: (1) 22,86 ± 10,52ng/ml; (2) 16,44 ± 11,02ng/ml; (3) 11,18 ± 5,87ng/ml respectively. Significant differences (F = 12.5, p = 0.001) were found in 1 vs. 2 and vs. 3. Significantly higher leptin levels were characteristic for women (F = 11.94, p = 0,001) in all groups. Mean IR in all groups were: (1) 0,17 ± 0,15, (2) 0,15 ± 0,05, (3) 0,17 ± 0,04 respectively. There were no statistical differences between groups. In group 1 a significant positive correlation was found between leptinaemia and mean SBP, HR, IR, BMI, waist circumference and percentage of adipose tissue mass, whereas in group 2 only between leptin level and mean SBP, HR and IR. Conclusions: The results indicate that in patients with metabolic syndrome leptin can participate in different mechanisms responsible for metabolic disorders. Positive correlations between leptin, IR, HR, SBP in both study groups suggest that leptin may contribute to blood pressure value through both sympathetic nervous system activity and insulin resistance irrespective of body mass.

Fasting plasma ghrelin in women with and without PCOS

Abstract Objectives To study the value of measuring ghrelin – a new marker for obesity – in Egyptian women with and without polycystic ovarian syndrome. Design Cross sectional study. Setting Kasr El-Aini Hospital, Cairo University. Materials and methods The study was conducted at Kasr Al-Aini Hospital, Faculty of medicine, Cairo University from February 2008 to January 2009. Sixty eight Egyptian females were divided into two groups according to their body mass index (BMI): average weight ( N =20) and obese ( N =48). This group was further subdivided into 2 subgroups (non-PCOS) group and PCOS group. Fasting leptin, ghrelin, insulin, glucose, lipid, urea and creatinine concentrations were determined. HOMA-IR was calculated. Results Ghrelin concentration decreased in obese women compared to normal weight subjects. Ghrelin levels were negatively correlated with BMI ( r =0.759), insulin ( r =−0.319), HOMA-IR ( r =−0.372). Leptin levels showed a positive correlation with BMI, insulin, HOMA-IR ( r =0.723, 0.284, 0.345, respectively). Glucose and insulin levels were significantly higher in the obese group compared to controls. To estimate the value of using ghrelin in predicting PCOS, a receiver operating characteristic curve (ROC) was plotted showing a sensitivity of 70% and specificity of 86% with a cut-off value of 34.1. Conclusions Ghrelin is a new marker that may be used for diagnosis of PCOS. Available data demonstrates a significant inverse relationship between ghrelin and leptin levels in obese women.

Carbohydrate restriction (with or without additional dietary cholesterol provided by eggs) reduces insulin resistance and plasma leptin without modifying appetite hormones in adult men

Carbohydrate-restricted diets (CRDs) have been shown to reduce body weight, whereas whole egg intake has been associated with increased satiety. The purpose of this study was to evaluate the effects of additional dietary cholesterol and protein provided by whole eggs while following a CRD on insulin resistance and appetite hormones. Using a randomized blind parallel design, subjects were allocated to an egg (640 mg/d additional dietary cholesterol) or placebo (0 mg/d additional dietary cholesterol) group for 12 weeks while following a CRD. There were significant reductions in fasting insulin (P < .025) and fasting leptin concentrations (P < .01) for both groups, which were correlated with the reductions in body weight and body fat (P < .05 and P < .01, respectively). Both groups reduced insulin resistance as measured by the homeostatic model assessment of insulin resistance (P < .025). There was a significant decrease in serum glucose levels observed after the intervention. We did not observe the expected increases in plasma ghrelin levels associated with weight loss, suggesting a mechanism by which subjects do not increase appetite with CRD. To confirm these results, the subjective measures of satiety using visual analog scale showed that both groups felt more "full" (P < .05), "satisfied" (P < .001), and "wanted to eat less" (P < .001) after the intervention. These results indicate that inclusion of eggs in the diet (additional dietary cholesterol) did not modify the multiple beneficial effects of CRD on insulin resistance and appetite hormones.