Antonio Liuzzi

Leptin plasma concentrations are dependent on body fat distribution in obese patients

AIM: To evaluate whether fat distribution plays a role in determining serum leptin concentrations.PATIENTS AND METHODS: One-hundred and forty-seven obese patients, 77 males and 70 females, aged 45.1±13.2u2005y (mean±s.d.; range 21–73u2005y), with body mass index (BMI) ranging from 30 to 55u2005kg/m2 (mean 42.3±5.9). Ultrasound assessment of the thickness of subcutaneous and preperitoneal fat was carried out and calculation of their ratio as abdominal fat index (AFI), waist–hip ratio (WHR), body composition by bioelectrical impedance to evaluate the percentage of fat mass (FM%) and total amount of fat (FMKg) were also determined. Plasma leptin was measured by radio immuno assay (RIA).RESULTS: In the whole group of patients, serum leptin concentrations were 37.2±18.4u2005ng/ml (range 6–101.3u2005ng/ml); in spite of BMI values not being significantly different, women had leptin values significantly higher (47.4±17.4u2005ng/ml) (P<0.01) than males (28.1±15.1u2005ng/ml), also after correction for fat mass. The mean thickness of abdominal subcutaneous fat was 33.7±12.9u2005mm and it was significantly (P<0.001) higher in female (40.9±10.6u2005mm) than in male (27.1±11.2u2005mm) patients; preperitoneal thickness was 22.9±7.1u2005mm, with significantly (P<0.05) higher values in males (24.2±6.8u2005mm) than in females (21.7±7.3u2005mm). Accordingly, AFI (in all patients 0.84±0.6) was significantly higher in males (1.09±0.6) than in females (0.56±0.2). In the overall population, leptin concentrations were directly and significantly related to subcutaneous but not preperitoneal fat; they showed a strong inverse relationship with AFI and WHR. When the results were evaluated dividing the patients according to gender, subcutaneous fat thickness showed a stronger association with leptin levels in males than in females, whereas no association was found with preperitoneal fat thickness. Leptin and AFI values were significantly related only in men. WHR values were not correlated with leptin concentrations in either sex. When fat mass was added to the model, subcutaneous fat thickness, AFI and WHR remained independently associated with leptin concentrations. Age and diabetes did not influence these measures.CONCLUSIONS: Fat distribution contributes to the variability in serum leptin in obese patients. In particular, subcutaneous abdominal fat is a determinant of leptin concentration, also independently of the amount of fat mass, whereas the contribution of preperitoneal visceral fat is not significant.

Low Doses of Dopamine Agonists in the Long-Term Treatment of Macroprolactinomas

To evaluate the long-term effects of dopamine agonists in the treatment of macroprolactinoma, we studied prolactin levels and tumor size for 30 to 88 months (57 +/- 14, mean +/- S.D.) in 38 patients treated with bromocriptine or lisuride. Elevated prolactin levels became normal in 30 patients, and the tumor shrank in 29. After two years of treatment, we attempted to reduce the maintenance dose (5 to 20 mg of bromocriptine per day or 0.4 to 0.8 mg of lisuride per day); in 21 patients no changes in prolactin levels or tumor size were observed over 6 to 52 months with 0.625 to 10 mg of bromocriptine per day or 0.05 mg of lisuride per day. However, it was possible to withdraw the drug in only one patient. We conclude that dopamine agonists are usually effective treatments for macroprolactinoma and that after a response has been obtained, it can be maintained in many patients with a greatly reduced dose.

Serum leptin concentration in moderate and severe obesity: relationship with clinical, anthropometric and metabolic factors

OBJECTIVE: To study clinical, anthropometric and metabolic determinants of serum leptin concentrations in a series of patients with a wide range of obesity.SUBJECTS: 400 patients, 116 males and 284 females, aged 44±12.3 years with body mass index (BMI) ranging from 31 to 82u2005kg/m2 (mean 41.4±7.1).MEASUREMENTS: Energy intake by 7-day recall, resting energy expenditure (REE) by indirect calorimetry, body composition determined by bioelectrical impedance; C index, an anthropometric index of abdominal fat distribution, and waist–hip ratio (WHR), blood glucose serum leptin concentrations, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, uric acid, and insulin concentrations HOMA IRI (homeostastis model assessment of insulin resistance index).RESULTS: Leptin concentrations were higher in obese than in normal subjects and in females than in males without differences between diabetic and non-diabetic patients; leptin concentrations were not related to age and showed a strong negative association with energy intake only in the group of women with BMI less than 40. Leptin concentrations showed a direct correlation with BMI and body fat values (expressed either as percentage of total body mass or absolute fat mass) independent of age and sex. After adjustment for fat mass, leptin values higher than predicted were found in women whereas concentrations lower than predicted were found predominantly in men. Leptin showed an inverse correlation with WHR and C-index, the latter persisting also after correction for gender and fat mass. REE, but not REE/kg fat-free mass (FFM) was inversely related to leptin also after correction for sex and absolute fat mass. Leptin concentrations were directly associated with HOMA IRI, insulin and HDL cholesterol and inversely associated with triglycerides and uric acid. The relationship of leptin with HOMA IRI was still evident after adjusting for sex but was lost when absolute fat mass was added to the model; HDL cholesterol and triglycerides appeared to be variables independent of leptin concentrations even when both sex and fat mass were added to the model.CONCLUSIONS: In a large group of obese patients (half of whom had severe obesity, gender, BMI and fat mass accounted for the largest proportion of serum leptin concentrations variability. We found that in obese subjects there is an effect of fat distribution on leptin concentrations and that, after excluding variability due to absolute fat mass, patients with a greater amount of abdominal fat have relatively low leptin concentrations which in turn relates to a metabolic profile compatible with an increased cardiovascular risk. Women with milder obesity may retain some degree of control of food intake by leptin.

Evaluation of a Multisensor Armband in Estimating Energy Expenditure in Obese Individuals

Objective: To examine the reliability and validity of the SenseWear Pro 2 Armband (SWA; Body Media, Pittsburgh, PA) during rest and exercise compared with indirect calorimetry (IC) in obese individuals.

Investigations of Thyroid Hormones and Antibodies in Obesity: Leptin Levels Are Associated with Thyroid Autoimmunity Independent of Bioanthropometric, Hormonal, and Weight-Related Determinants

OBJECTIVESnObesity can alter the thyroid hormone status as a result of a dysregulated endocrine loop between the hypothalamo-pituitary unit and adipose tissue. The adipocytokine leptin has been shown to promote autoimmunity; hence, we aimed to clarify whether leptin excess of obesity could increase the susceptibility to develop autoimmune thyroid disease (AITD).nnnSTUDY DESIGNnThis cross-sectional study was performed in a tertiary care center.nnnMETHODSnFree thyroid hormones, TSH, thyroglobulin, and antithyroid antibodies levels were tested in 165 obese and 118 lean subjects. Results were plotted against variables related to body composition, leptin levels, glucose homeostasis, energy expenditure, and pattern of weight accrual.nnnRESULTSnCompared with controls, obese patients had lower free T3 levels and free T4 levels (P<0.01), greater prevalence of hypothyroidism (P<0.05), and higher commonness of antithyroid antibodies (P<0.05). As a marker of AITD, thyroid peroxidase antibodies were more frequent in the obese group (P<0.01). Correlation analysis showed that leptin levels were associated with AITD (P<0.01) independent of bioanthropometric variables. Multiple logistic regression analysis in pooled groups identified female sex and leptin as significant predictors of AITD.nnnCONCLUSIONSnObesity increases the susceptibility to harbor AITD with an emerging role for leptin as a peripheral determinant, which needs to be confirmed in future investigations.

Glucose homeostasis in acromegaly: effects of long‐acting somatostatin analogues treatment

objectiveu2002 Acromegaly is a syndrome with a high risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). Somatostatin analogues, which are used for medical treatment of acromegaly, may exert different hormonal effects on glucose homeostasis. Twenty‐four active acromegalic patients were studied in order to determine the long‐term effects of octreotide‐LAR and SR‐lanreotide on insulin sensitivity and carbohydrate metabolism.

Deep Subcutaneous Adipose Tissue: A Distinct Abdominal Adipose Depot

Objective: Abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) display significant metabolic differences, with VAT showing a functional association to metabolic/cardiovascular disorders. A third abdominal adipose layer, derived by the division of SAT and identified as deep subcutaneous adipose tissue (dSAT), may play a significant and independent metabolic role. The aim of this study was to evaluate depot‐specific differences in the expression of proteins key to adipocyte metabolism in a lean population to establish a potential physiologic role for dSAT.

Free and bound plasma leptin in normal weight and obese men and women: relationship with body composition, resting energy expenditure, insulin-sensitivity, lipid profile and macronutrient preference.

Objectiveu2002 The adipose‐borne hormone leptin circulates in free and protein‐bound forms but little information is available about their biological significance. Free leptin (FL) levels are related to changes in fat mass, whereas bound leptin (BL) appears to be associated with resting energy expenditure (REE). Our aim was to assess FL and BL levels in normal weight and obese subjects and correlate them with metabolic and nutritional variables.

Sporadic mutations in melanocortin receptor 3 in morbid obese individuals

Several mutations in the melanocortin receptor 4 gene have been identified in humans and account for 3–6% of morbid obesity. In contrast, strong evidence of a causative role for melanocortin receptor 3 (MC3R) mutations are still lacking. In MC3R knockout mice, high feed efficiency rather than hyperphagia seems to contribute to increased fat mass. On the basis of this evidence, the objective of the present study was to investigate the presence of MC3R mutations in a group of 290 obese subjects (mean BMI 44.2±5.9u2009kg/m2). As a control, a group of 215 normal-weight subjects (mean BMI 22.4±2.7u2009kg/m2) was also screened. Three novel mutations in the MC3R gene (A293T, I335S and X361S) were identified among the obese patients. The mutations segregated with obesity in the members of the families studied. In vitro expression studies of each mutation demonstrated a loss of function of the I335S-mutated receptor. These findings suggest that, in humans, MC3R mutations may be a cause of a dominantly inherited form of obesity. However, this association as well as the specific phenotypic characteristics resulting from these mutations need to be further evaluated in larger series of obese subjects.

Acylated ghrelin decreases during acute exercise in the lean and obese state

Ghrelin, the GH-secretagogue receptor ligand, is chiefly acknowledged as a central modulator of energy homeostasis. 1 In addition to promoting the drive to eat and governing long-term energy accumulation, ghrelin has been shown to influence fuel oxidation, increase the respiratory exchange ratio (RER), decrease spontaneous physical activity and enhance cardiac function. 1 In the bloodstream, ghrelin circulates both as an acylated and desacylated peptide. Ghrelin concentrations are acutely suppressed after food ingestion or glucose infusion, while fat accumulation is a long-term negative regulator. 2,3 Recent studies in lean individuals prompted debated evidence that acute exercise decreases total and acylated ghrelin levels in relation to GH concentrations and perceived appetite ratings. 4–6