Fasting Serum Leptin Concentrations Research Articles

Decreases in fasting leptin and insulin concentrations after acute energy restriction and subsequent compensation in food intake

The decrease in leptin after energy restriction is a starvation signal to the brain. Several studies have found an association between this decrease and subjective appetite; however, no solid data are available on the acute decrease in fasting leptin concentration and subsequent caloric compensation. The objective was to assess the effect of acute decreases in fasting leptin concentrations, induced by energy restriction, on subsequent energy intake compensation. We hypothesized that men with a large decrease in fasting leptin concentrations would have larger ad libitum energy intakes than would men with a small decrease in leptin. Thirty-four male unrestrained eaters [age: 23 +/- 3 y; body mass index (in kg/m(2)): 22.3 +/- 1.6] participated in a semicontrolled intervention study. Fasting serum leptin and insulin concentrations were measured before and 2 d after 62% energy restriction. Energy intake was measured on the 2 following days on which food was provided ad libitum. During energy restriction, fasting leptin and insulin concentrations decreased by 27.2% (95% CI: -34.4%, -19.9%) and 30.7% (95% CI: -41.0%, -20.4%), respectively. Subjects consumed 143 +/- 27% of their estimated energy requirements (18.3 +/- 2.9 MJ) on the first day and 124 +/- 20% (16.0 +/- 2.6 MJ) on the second day of ad libitum intake. No significant correlations were observed between decreases in fasting leptin or insulin concentrations and subsequent ad libitum energy intake; however, decreases in insulin were correlated with an increase in carbohydrate intake (r=-0.49, P < 0.01). Although fasting leptin concentrations decreased significantly during energy restriction and subjects showed compensatory behavior during subsequent ad libitum food intake, no association was observed between the decrease in fasting leptin concentrations and caloric compensation.

Serum leptin concentrations and body adipose measures in older black and white adults

Among US adults, serum leptin concentrations are higher in women than in men and are higher in blacks than in whites independent of anthropometric measures of body fatness. Using radiographic measures of body fat, we determined the best correlates of leptin and whether adiposity can explain sex and race differences in leptin concentrations in older adults. This was a cross-sectional analysis of fasting serum leptin concentrations and body fat measured by dual-energy X-ray absorptiometry (DXA), abdominal computed tomography, and standard anthropometry in 3026 well-functioning 70-79-y-old participants (42% black, 51% women) of the Health, Aging, and Body Composition Study. Geometric mean (+/-SE) leptin concentrations (ng/mL) were higher in the women than in the men (16.5 +/- 0.3 and 5.7 +/- 0.1, respectively) and in the black women than in the white women (20.2 +/- 0.6 and 13.9 +/- 0.4, respectively), but did not differ significantly between the white and black men (5.8 +/- 0.2 and 5.5 +/- 0.2, respectively). Percentage fat estimated from DXA showed the highest correlation with leptin (R(2) = 0.56 for both sexes). Addition of abdominal visceral fat minimally increased the correlation. In the multivariate analysis, the association with sex was eliminated after adjustment for percentage fat and visceral fat in both whites (P = 0.051) and blacks (P = 0.34). Among women, higher leptin concentrations in blacks remained after adjustment for percentage fat and visceral fat (mean race difference = 4.95 ng/mL; P < 0.001). Among men, an association with black race emerged after adjustment for these factors (mean race difference = 1.42 ng/mL; P < 0.001). Among older adults, higher serum leptin concentrations in women are explained by a greater percentage of body fat. Higher leptin concentrations in blacks are not explained by percentage of body fat.

Increased leptin concentrations and lack of gender difference in Type 2 diabetic patients with nephropathy

Leptin plays an important role in the regulation of body weight and energy balance. Women have higher circulating leptin level than men. In this study, we examined serum leptin concentrations in Type 2 diabetic men and women with or without nephropathy. Fasting plasma glucose (FPG), lipid profile, and serum leptin concentrations were measured in 34 Type 2 diabetic patients with nephropathy (DMN), 12 normoalbuminuric Type 2 diabetic subjects (DM) and 34 non-diabetic control subjects, all matched for age and body mass index (BMI). Result: Patients with diabetic nephropathy had lower high-density lipoprotein cholesterol and higher triglyceride, FPG, urinary albumin/creatinine ratio (ACR) and serum creatinine than the other two groups. There was a significant trend in serum leptin concentrations ( P<0.001, analysis of variance ANOVA) across the three groups with the main difference being detected between DMN and control subjects (DMN: 17.5±16.8 ng/ml, DM: 14.6±10.5 ng/ml and control: 9.1±7.1 ng/ml). Women had higher serum leptin concentration than men in the control group (12.5±7.3 ng/ml versus 4.2±2.0 ng/ml, P=0.001) and in the DM group (18.9±11 ng/ml versus 8.6±5.9 ng/ml, P=0.07) whereas this gender difference was not observed in the DMN group (18.6±17.0 ng/ml versus 16.8±17.0 ng/ml, P=0.754). On multivariate analysis, ACR ( β=0.411, P<0.001) and BMI ( β=0.240, P=0.002) were independently associated with serum leptin concentrations ( R 2=0.194, F=22.1, P<0.001) in the whole group. In the DMN group, ACR ( β=0.370, P=0.016) was the only independent determinant of serum leptin concentrations ( R 2=0.159, F=11.4, P=0.016). Serum leptin concentrations were higher in Type 2 diabetic patients with nephropathy than normoalbuminuric diabetic patients and controls. Diabetic men with nephropathy had proportionally higher serum leptin such that the gender difference in leptin observed in non-nephropathic individuals was abolished.

Specific features of leptin secretion in children and adolescents with obesity

The purpose of the study was to examine baseline leptin secretion and its association with insulin secretion in children and adolescents with obesity and in those having normal body weight. Sixty- six children and adolescents aged 11-16years, including 48 individuals with obesity, were examined. Anthropometric indices, fasting serum leptin concentrations, and the time course of changes during a three-hour oral glucose test were assessed. In obese children and adolescents, the baseline level of leptin was significantly higher than in normally weighing children and adolescents of the same age. Abdominovisceral obesity showed a higher level of leptin than gluteofemoral obesity. Age- and gender-specific features of leptin production were revealed in obese children and adolescents. There was an association of leptin production with anthropometric indices. Children and adolescents with obesity showed a positive correlation of the baseline level of leptin with overall insulin secretion during the oral test and a negative correlation of the baseline level of leptin with the insulin sensitivity index.

Serum leptin concentrations in children with mild-to-moderate protein-energy malnutrition.

The aim of the present study was to clarify the relationship between nutritional anthropometric parameters and serum leptin concentrations in otherwise healthy children with mild-to-moderate protein-energy malnutrition (PEM) secondary to inadequate energy intake. Eighty-one otherwise healthy children with poor appetite and inadequate energy intake were enrolled in the study. The anthropometric values were evaluated in all subjects. Fasting serum leptin concentrations were assessed. Of the 81 otherwise healthy children, 30 were found to have mild-to-moderate PEM. The control group consisted of 51 healthy children who had normal anthropometric values, even though they had inadequate energy intake. There was a significant difference in serum leptin concentrations between the two groups (P < 0.01). Furthermore, there was a positive correlation between mean serum leptin concentrations and percentage of standard weight for height in the patient and the control group (P < 0.05). Multiple linear regression analysis indicated that percentage of standard BMI was the best predictor for serum leptin concentrations (P < 0.05). In addition to BMI, percentage of standard weight for height is a valuable nutritional anthropometric parameter for serum leptin concentrations in PEM and inadequate energy intake. However in the present study, percentage of standard BMI was the best predictor for serum leptin concentrations. Serum leptin concentrations are low not only in severe PEM, but also in children with mild-to-moderate PEM without chronic disease.

Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus

The aim of the present study was to investigate the association of serum adiponectin concentration with regional adiposity and insulin resistance in subjects with type 2 diabetes mellitus. A total of 73 Japanese men with type 2 diabetes (aged 59 ± 11 years and body mass index [BMI] 23.8 ± 3.0 kg/m 2, mean ± SD) were studied. Fasting serum adiponectin and leptin concentrations were determined by radioimmunoassay. Regional adiposity was measured by abdominal computed tomography (CT) at the umbilical level, and insulin resistance was estimated by homeostasis model assessment (HOMA-R). Univariate regression analysis showed that serum adiponectin levels were negatively correlated with subcutaneous and visceral fat areas. With multivariate regression analysis, visceral fat area was a predominant determinant of serum adiponectin levels. In contrast, subcutaneous fat area was strongly associated with serum leptin concentrations. Among subcutaneous and visceral fat areas, BMI, and serum leptin levels, both subcutaneous and visceral fat areas were independently associated with HOMA-R. In another model incorporating serum adiponectin levels, serum adiponectin levels were selected as an independent determinant of HOMA-R instead of visceral fat area. In conclusion, hypoadiponectinemia was associated with visceral fat accumulation rather than subcutaneous fat depot in Japanese men with type 2 diabetes mellitus. Both subcutaneous and visceral fat accumulation contribute to insulin resistance in these subjects, and the contribution of visceral fat may be mediated, in part, by hypoadiponectinemia.

Relationship Between Fasting Leptin and Insulin Concentrations in Type 2 Diabetes Mellitus Patients

Objectives: Many researchers have found that plasma leptin concentration is associated with insulin levels in non-diabetic subjects. However, the relationship between leptin concentrations and insulin levels in type 2 diabetes mellitus (DM) patients has rarely been investigated. The aim of this study was to investigate that relationship. Methods: Fasting plasma glucose, fasting serum insulin (FSI), leptin concentration and body mass index (BMI) were measured in 100 type 2 DM subjects (50males and 50 females). Results: There were no significant differences in age, BMI, fasting plasma glucose, FSI and HbAlc between male and female subjects. The mean leptin concentration of the female subjects was significantly higher than that of the male subjects (7.75 ± 6.41 vs 3.72 ± 3.70ng/mL, ρ＜ 0.01). Using Pearson correlation analysis, leptin concentration positively correlated with BMI (γ=0574, ρ＜ 0.001) and FSI levels (γ= 0.498, ρ＜ 0.001) in the male subjects. It also positively correlated with BMI (γ= 0.605, ρ＜ 0.001) and FSI levels (γ= 0.543, ρ＜ 0.001) but inversely correlated with age (γ = -0.399, P = 0.004) in the female subjects. After adjusting for age, BMI, and insulin modifying medications, FSI was significantly and positively related to leptin concentration (β= 0.180, ρ=0.031) in the male subjects but not in the female subjects (β= 0.131, ρ= 0.089). BMI also positively correlated with leptin concentrations in both genders after considering the effects of FSI and other covariates. Conclusions: Leptin concentration significantly correlated with FSI levels in men with type 2diabetes but not in women with type 2 diabetes. The difference between the two groups may be due to age, gender effect, or other potential confounders. Further investigation is necessary.

Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States

Background & Aims: In the absence of other causes, overweight and obesity increase the risk of liver disease. We examined whether central adiposity and metabolic markers explain the association of body mass index (BMI as kg/m2) with abnormal serum alanine aminotransferase (ALT) activity in a national, population-based study. Methods: Adult participants (5724) in the third U.S. National Health and Nutrition Examination Survey (1988–1994) underwent anthropometric measures and phlebotomy after an overnight fast. Participants with excessive alcohol consumption, hepatitis B, hepatitis C, iron overload, or known diabetes were excluded. Results: Elevated ALT levels were found in 2.8% of the population. In univariate analysis, factors associated with elevated ALT levels (P < 0.05) included younger age, male sex, Mexican-American ethnicity, and higher BMI, waist-to-hip circumference ratio (WHR), and fasting serum leptin, triglyceride, insulin, and glucose concentrations. The proportion of elevated ALT activity due to overweight and obesity (BMI ≥25 kg/m2) was 65%. In multivariate logistic regression analysis, control for WHR, demographic factors, and glucose concentration diminished but did not eliminate the association of higher BMI with elevated ALT activity. After adding leptin and insulin concentrations, abnormal ALT activity was most strongly associated with higher WHR (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.12–1.56) and leptin (OR, 1.12; 95% CI, 1.01–1.24) and insulin (OR, 1.27; 95% CI, 1.01–1.60) concentrations, whereas BMI was not independently related. Conclusions: In this large, national, population-based study, central adiposity, hyperleptinemia, and hyperinsulinemia were the major determinants of the association of overweight with elevated serum ALT activity.GASTROENTEROLOGY 2003;124:71-79

Influence of leptin on arterial distensibility: a novel link between obesity and cardiovascular disease?

The mechanisms by which obesity increases the risk of atherosclerotic cardiovascular disease (CVD) are poorly understood. In experimental models, leptin, a hormone produced by adipose tissue, has been shown adversely to affect vascular health. Therefore, we tested the hypothesis that high leptin concentrations are associated with lower arterial distensibility, an index of circulatory function relevant to the atherosclerotic process. Noninvasive, high-resolution, vascular ultrasound was used to measure brachial artery distensibility in 294 healthy adolescents (aged 13 to 16 years) who had a broad range of body mass indexes. Fat mass was measured by bioelectric impedance analysis; fasting serum leptin concentration by radioimmunoassay; and lipid profile, fasting insulin, glucose, and C-reactive protein concentrations by standard laboratory techniques. Higher leptin concentrations were associated with impaired arterial distensibility (regression coefficient, -1.3% change in arterial distension per 10% increase in leptin; 95% CI, -1.9% to -0.8%; P<0.001). This association was independent of fat mass, blood pressure, and C-reactive protein, fasting insulin, or LDL cholesterol concentrations. Elevation in leptin was associated with impaired vascular function, independent of the metabolic and inflammatory disturbances associated with obesity. Our observations are consistent with data from experimental models and suggest that high leptin concentration is an important mechanism for the adverse influence of body fatness on CVD.

Children with classic congenital adrenal hyperplasia have elevated serum leptin concentrations and insulin resistance: potential clinical implications.

Leptin is secreted by the white adipose tissue and modulates energy homeostasis. Nutritional, neural, neuroendocrine, paracrine, and autocrine factors, including the sympathetic nervous system and the adrenal medulla, have been implicated in the regulation of leptin secretion. Classic congenital adrenal hyperplasia (CAH) is characterized by a defect in cortisol and aldosterone secretion, impaired development and function of the adrenal medulla, and adrenal hyperandrogenism. To examine leptin secretion in patients with classic CAH in relation to their adrenomedullary function and insulin and androgen secretion, we studied 18 children with classic CAH (12 boys and 6 girls; age range 2-12 yr) and 28 normal children (16 boys and 12 girls; age range 5-12 yr) matched for body mass index (BMI). Serum leptin concentrations were significantly higher in patients with CAH than in control subjects (8.1 +/- 2.0 vs. 2.5 +/- 0.6 ng/ml, P = 0.01), and this difference persisted when leptin values were corrected for BMI. When compared with their normal counterparts, children with CAH had significantly lower plasma epinephrine (7.1 +/- 1.3 vs. 50.0 +/- 4.2, P < 0.001) and free metanephrine concentrations (18.4 +/- 2.4 vs. 46.5 +/- 4.0, P < 0.001) and higher fasting serum insulin (10.6 +/- 1.4 vs. 3.2 +/- 0.2 microU/ml, P < 0.001) and testosterone (23.7 +/- 5.3 vs. 4.6 +/- 0.5 ng/dl, P = 0.003) concentrations. Insulin resistance determined by the homeostasis model assessment method was significantly greater in children with classic CAH than in normal children (2.2 +/- 0.3 vs. 0.7 +/- 0.04, P < 0.001). Leptin concentrations were significantly and negatively correlated with epinephrine (r = -0.50, P = 0.001) and free metanephrine (r = -0.48, P = 0.002) concentrations. Stepwise multiple linear regression analysis indicated that serum leptin concentrations were best predicted by BMI in both patients and controls. Gender predicted serum leptin concentrations in controls but not in patients with classic CAH. No association was found between the dose of hydrocortisone and serum leptin (r = -0.17, P = 0.5) or insulin (r = 0.24, P = 0.3) concentrations in children with CAH. Our findings indicate that children with classic CAH have elevated fasting serum leptin and insulin concentrations, and insulin resistance. These most likely reflect differences in long-term adrenomedullary hypofunction and glucocorticoid therapy. Elevated leptin and insulin concentrations in patients with CAH may further enhance adrenal and ovarian androgen production, decrease the therapeutic efficacy of glucocorticoids, and contribute to later development of polycystic ovary syndrome and/or the metabolic syndrome and their complications.

Relationship of serum leptin concentration and other measures of adiposity with gallbladder disease

Obesity increases the risk of gallstones, especially in women. Most gallbladder disease studies have used body mass index (BMI) as a measure of overall adiposity, although BMI does not distinguish between fat and lean body mass. Central adiposity may also increase gallstone risk, although this is less well studied. Leptin is a peptide whose serum concentration is highly correlated with total body fat mass. We examined the relationship of gallbladder disease with anthropometric measures and serum leptin concentration in a large, national, population-based study. A total of 13,962 adult participants in the Third National Health and Nutrition Examination Survey underwent gallbladder ultrasonography and anthropometric measurements of BMI, body circumferences, and skinfold thicknesses, and a random subgroup of 5,568 had measures of fasting serum leptin concentrations. Gallstone-associated gallbladder disease was defined as ultrasound-documented gallstones or evidence of cholecystectomy. When controlling for BMI and other gallbladder disease risk factors in multivariate analysis, a test for trend for increasing waist-to-hip circumference ratio and risk of gallbladder disease was statistically significant among women (P = .043) and men (P = .007). BMI remained strongly associated with gallbladder disease among women (P < .001), but was unrelated among men (P = .46). Leptin concentration was associated with gallbladder disease in both sexes (P < .001), but not after controlling for BMI and waist-to-hip circumference in either women (P = .29) or men (P = .65). In conclusion, waist-to-hip circumference ratio was related to gallbladder disease among women and men. Serum leptin concentration was not a better predictor of gallbladder disease than anthropometry. (HEPATOLOGY 2001;34:877-883.)

Effects of selected minerals on leptin secretion in streptozotocin-induced hyperglycemic mice.

The effects of lithium, magnesium, vanadate, and zinc on leptinemia and leptin secretion by adipose tissue were investigated in streptozotocin- (STZ) induced hyperglycemic mice. After the administration of studied minerals in drinking water for 4 weeks, fasting serum leptin concentrations were elevated, accompanied by normoglycemia in STZ-injected mice, regardless which mineral was provided (P < 0.05). However, the in vitro administration of lithium, magnesium, and vanadate did not significantly influence the leptin secretion of adipose tissue. A low zinc treatment (0.1 mM) augmented, whereas both a pharmacological treatment of zinc (1 mM) and zinc depletion (1 mM TPEN) attenuated, leptin secretion (P < 0.05). The present study shows that STZ-induced hyperglycemic mice have hypoleptinemia and reduced leptin secretion by adipose tissue. Moreover, these defects can be improved by a moderate zinc administration.

Leptin concentrations in the United States: relations with demographic and anthropometric measures

Leptin is a peptide that is strongly correlated with adiposity and is a potential determinant of obesity and its complications. Leptin concentrations from a representative sample of the US population were examined in relation to demographic and anthropometric measures. Fasting serum leptin concentrations were measured in 6303 women and men aged > or =20 y in the third National Health and Nutrition Examination Survey. Anthropometric measures included body mass index, 4 skinfold thicknesses, and 4 body circumferences. Ethnic groups included non-Hispanic whites and blacks and Mexican Americans. The mean serum leptin concentration was much higher in women (12.7 microg/L) than in men (4.6 microg/L). In a multivariate analysis, leptin concentrations were associated with the sum of 4 skinfold thicknesses, waist and hip circumferences, ethnicity, and age. These measures explained most of the variance in leptin concentrations in women (R2 = 0.69) and in men (R2 = 0.67). Triceps skinfold thickness, when substituted for the sum of skinfold thicknesses, performed nearly as well in women (R2 = 0.68) and men (R2 = 0.67). Leptin concentrations were slightly but significantly higher in non-Hispanic blacks than in non-Hispanic whites of both sexes when these anthropometric measures and age were controlled for; Mexican Americans had concentrations that were intermediate compared with the concentrations of non-Hispanic whites and blacks. In this large, representative sample of the US population, demographic and anthropometric measures predicted serum leptin concentrations in women and men.

Weight loss is not associated with hyperleptinemia in humans with pancreatic cancer.

Pathological weight loss is a feature of many diseases and contributes to mortality and morbidity. Although cytokines have been implicated in some models of pathological weight loss, little is known about cellular mechanisms responsible for cachexia in patients with cancer. Leptin is a fat cell product that acts centrally to reduce appetite and decrease metabolism. Leptin synthesis is stimulated by cytokines, and circulating levels of cytokines are elevated in some cancer patients. We hypothesized that cytokine-induced hyperleptinemia contributes to pathological weight loss in patients with pancreatic cancer. To evaluate this hypothesis, fasting serum leptin concentrations were measured in 64 patients undergoing surgery for pancreatic cancer. Preoperative interviews were used to assess body weight and appetite history. Thirty of 64 pancreatic cancer patients had cachexia (weight loss of >10% over the 6 months before surgery). Self-reported loss of appetite was associated with the presence of cachexia. Leptin concentrations, when corrected for body mass index, were lower than levels reported in healthy humans. Six patients had leptin levels more than 2 times those predicted by body mass index. There was no association between patients with increased leptin concentration and weight loss or anorexia. We conclude that a reduced appetite contributes to weight loss in patients with pancreatic cancer. High plasma leptin levels, however, do not appear to contribute to cachexia in these patients.

Leptin and other components of the Metabolic Syndrome in Mauritius--a factor analysis.

To use factor analysis to examine the putative role of leptin in the Metabolic Syndrome, and to define better the associations among observed variables and the identified factors. Factor analysis of cross-sectional data from a 1987 survey. Non-diabetic residents of Mauritius who participated in population-based surveys in 1987 and 1992 (1414 men and 1654 women). Fasting and 2 h plasma glucose and insulin following a 75 g oral glucose load; seated blood pressure; body mass index (BMI); waist-to-hip ratio (WHR); and fasting serum triglycerides, HDL-cholesterol, leptin and uric acid concentrations. Principal components factor analysis revealed three factors for men and women that explained between 54 and 55% of the observed variance of the 12 measured variables. General features of these factors were as follows: factor 1, WHR, BMI, leptin, fasting and 2 h insulin, triglycerides, and HDL-cholesterol; factor 2, systolic and diastolic blood pressure, uric acid (men only), and fasting glucose (women only); and factor 3, fasting and 2 h glucose and insulin. Only three variables loaded on more than one factor with a loading > or = 0.4 (fasting and 2 h insulin, fasting glucose in women only). Leptin loaded on one factor only in both men and women. Since multiple factors underlie the Metabolic Syndrome, and since no observed variable loads on all three factors, more than one mechanism might account for the observed clustering of risk characteristics. Leptin does not unite features of this syndrome due to its loading on one factor only. Uric acid is related to a different factor in men and women. The absence of gender differences in factor loadings argues for similar mechanisms for the Metabolic Syndrome in men and women in Mauritius. International Journal of Obesity (2001) 25, 126-131

Determinants of within-subject variation of fasting serum leptin concentrations in healthy subjects.

The hormone leptin is considered to contribute to body weight regulation through modulation of feeding behavior and energy expenditure. The aim of the present study was 1) to assess the day-to-day within-subject variation (biovariability) of serum leptin concentrations in healthy subjects and 2) to investigate whether this variation is associated with food intake, exercise, anthropometric measurements or various metabolic covariates (insulin, C-peptide and glucagon, glucose, lactate, 3-hydroxybutyrate (3-OHB), triglycerides, non-esterified-fatty acids and glycerol). Serum leptin levels were taken daily on 12 consecutive days after an overnight fast in 12 healthy subjects with a mean (SD) age of 22.7 (1.5) yr. and a BMI of 22.8 (1.6) kg/m2. Food intake, exercise, anthropometric measurements and various metabolic covariates were also determined during this period. The overall mean of serum leptin concentration was 33.3 pmol/L with a within-subject SD range of 27-41 pmol/L and a between-subject SD range of 18-61 pmol/L. The within-subject variance of serum leptin as a proportion of total variance was 9.5%. Within-subject variation of serum leptin concentrations is small in relation to between-subject variation in healthy, normal weight subjects. This has implications for the power of interventional or prospective studies. In men, 6.7% of the variation in serum leptin concentration was associated with body weight measured on the same day (p= 0.037). In women, however, 66% of the variation was negatively associated with 3-OHB measured on both the same and the previous day (p=0.0003 and 0.002), and positively associated with triglyceride concentration measured on the previous day (p=0.0017) and insulin measured on the same day (p=0.0002). Within-subject associations in women could be due to phasic changes in unmeasured variables, possibly related to the menstrual cycle or might suggest that energy balance may exert a delayed influence on serum leptin levels, with plasma 3-OHB and triglycerides acting as markers for the state of the fat stores that regulate leptin secretion. The differences between the genders remain unexplained, however.

Serum leptin and leptin receptors in healthy prepubertal children: relations to insulin resistance and lipid parameters, body mass index (BMI), tumor necrosis factor alpha (TNF alpha), heart fatty acid binding protein (hFABP), and IgG anticardiolipin (ACL-IgG).

In a group of randomly selected 29 healthy prepubertal children (16 boys, mean age 9.56 +/- 0.7 years, 13 girls, mean age 9.96 +/- 0.9 years) fasting serum leptin and leptin receptor concentrations were measured by ELISA and compared with insulin parameters (homeostatic model of assessment insulin resistance = HOMA IR, insulin, intact proinsulin, C-peptide) and some metabolic parameters and factors that contribute to insulin resistance: triacylglycerols, high density lipoprotein cholesterol (HDL cholesterol), low density lipoprotein cholesterol, body mass index, tumor necrosis factor, heart fatty acid binding protein, and IgG fraction of anticardiolipin. Statistical analysis was performed using SAS/STAT software and included analysis of normality, analysis of variance, Spearman's correlations, linear and multiple regression analysis with insulin parameters as dependent variables. The subgroups of boys and girls did not differ significantly in any of parameters studied. Serum concentrations of insulin, intact proinsulin, HOMA IR, C-peptide and triacylglycerols appeared to be primarily influenced by serum leptin concentration. Serum leptin concentrations were tightly correlated with body mass indexes and negatively correlated with leptin receptor concentrations, probably as a manifestation of down regulation. The role of other factors studied appeared to be complementary or less significant (hFABP, ACL IgG), or absent (TNF alpha). We concluded that in healthy prepubertal children of both genders serum leptin concentration contributes to insulin resistance and to insulin resistance-related metabolic changes.

Serum leptin concentrations in children with Prader-Willi syndrome and non-syndromal obesity.

There is limited information on the underlying physiological mechanisms promoting obesity in patients with Prader-Willi syndrome (PWS). The aim of this study was to investigate whether body fat regulation in children with PWS is similar to that in children with non-syndromal obesity and non-obese children. We studied three groups: 1) 72 non-obese children and adolescents; 2) 68 children with non-syndromal obesity; and 3) 11 patients with PWS. Height and weight were measured and body mass index (BMI) and BMI SDS were calculated. Fasting serum leptin concentrations were determined. Median leptin serum concentrations were similar in PWS patients and children with non-syndromal obesity. Median leptin serum concentrations were higher in these two groups than in the non-obese group. Log leptin serum concentrations and BMI SDS showed significant correlations in the three groups of patients; correlation coefficients were 0.525, 0.285 and 0.854, respectively. In conclusion, median leptin serum concentrations are similar in PWS patients and children with non-syndromal obesity. The relationship between log serum leptin concentrations and BMI SDS was different in the three groups of patients studied.

An uncoupling protein 2 gene variant is associated with a raised body mass index but not Type II diabetes.

Linkage between markers close to the uncoupling protein 2 and 3 genes (11q13) and resting metabolic rate and a pre-diabetic phenotype have been found. The syntenic region in mouse has been found to be linked to quantitative traits associated with obesity and diabetes. UCP2 and UCP3 could therefore have an important role in body weight regulation and susceptibility to diabetes. We investigated a recently identified variant of the UCP2 gene in exon 8 as a marker for glucose and weight homeostasis. Length variation of the UCP2 exon 8 variant was studied by the polymerase chain reaction and agarose gel electrophoresis. Sequence variants of the UCP3 gene were sought by semi-automated DNA sequencing. In 453 South Indian subjects, we found an association in women between the UCP2 exon variant and body mass index (p = 0.018). These findings were replicated in a separate group of South Indian subjects (n = 143, p < 0.001) irrespective of sex. Although no association was found between the UCP2 exon 8 variant and overt obesity in British subjects, the UCP2 genotype of obese women (n = 83) correlated with fasting serum leptin concentration (p = 0.006) in the presence of extreme obesity. These observations could not be explained by tight linkage disequilibrium with a coding region variant in the region of the UCP3 gene of biological significance. Lastly, no association was found between UCP2 and Type II (non-insulin-dependent) diabetes using either a family based design (85 families) or case control study (normal glucose tolerance n = 335, impaired glucose tolerance n = 42, Type II diabetes n = 76). We have described a UCP2 gene exon 8 variant that may affect susceptibility to weight gain by influencing regulation of leptin.

Serum leptin concentrations and their relation to metabolic abnormalities in human sepsis.

Circulating leptin concentrations are raised in animal models of inflammation and sepsis. The purpose of this study was to determine the effect of sepsis on serum leptin concentration in humans and to examine the relationship between leptin and the metabolic consequences of sepsis. Resting energy expenditure, insulin sensitivity, and fasting serum leptin, plasma insulin, and cortisol concentrations were measured in 20 subjects with intra-abdominal sepsis and 20 healthy control subjects, before and during a 2-h period of euglycemic hyperinsulinemia. Fasting serum leptin concentrations were similar in septic and control subjects. In simple regression analysis, serum leptin concentrations correlated significantly with percent body fat in both septic patients (r = 0. 64, P < 0.005) and healthy subjects (r = 0.75, P < 0.0001). Multiple regression analyses additionally indicated that percent body fat, fasting plasma insulin, and plasma cortisol, but not sepsis, were significant and independent determinants of serum leptin concentration. No relationship between leptin and resting energy expenditure or insulin sensitivity was identifiable. A major metabolic role for leptin in human sepsis therefore appears unlikely.