Permanence of molecular features of obesity in subcutaneous adipose tissue of ex-obese subjects.

OBJECTIVE: Bariatric surgery represents a powerful tool for morbid obesity treatment. However, after stabilization of weight loss that follows surgical interventions, ex-obese patients face the problem of residual tissues removal. Actually, it is unknown whether the characteristics of this residual subcutaneous adipose tissue (SAT) are 'restored' with regard to molecular and morphological features. DESIGN: To clarify this issue, we compared the SAT gene expression profile of ex-obese patients (ExOB-SAT, mean body mass index (BMI): 27.2±1.3 kg m(-2)) with that of lean (normal weight, NW-SAT, mean BMI: 22.6±1.1 kg m(-2)), overweight (OW-SAT, BMI: 27.65±0.2 kg m(-2)) and obese patients, according to BMI classes (OB1-SAT: 30 > or = BMI < or = 34.9, OB2-SAT: 35 > or = BMI < or = 39.9, OB3-SAT: BMI > or = 40). SUBJECTS AND METHODS: A total of 58 samples of SAT were collected during surgical interventions. Gene expression levels were assessed by microarrays and significant genes were validated by RT-qPCR. Adipocyte hypertrophy, inflammatory infiltration and fibrosis were assessed by morphological techniques. RESULTS: Global gene expression in ExOB-SAT was closely related to gene expression of OB3-SAT by hierarchical clustering procedures, in spite of different BMI. Metallothioneins (MT1A and MT2A) were the key over-expressed genes in both groups. At morphologic level, adipocyte hypertrophy and inflammatory infiltration improved after weight loss in ExOB-SAT, despite a persistence of fibrosis. CONCLUSIONS: Taken together, these results demonstrate that SAT gene expression is not fully restored, even after an extensive and stable weight loss. The persistence of 'obesity molecular features' in ExOB-SAT suggests that the molecular signature of adipose tissue is not solely dependent on weight loss and may need longer time period to completely disappear.

The nicotinic acetylcholine receptor α7 in subcutaneous mature adipocytes: downregulation in human obesity and modulation by diet-induced weight loss.

BACKGROUND: It is known that cholinergic anti-inflammatory reflex regulates inflammation in peripheral tissues. Nicotinic acetylcholine receptors (nAChRs) are mediators of this anti-inflammatory pathway and also non-neuronal cells express functional nAChrs. A role for α7-subtype acetylcholine cholinergic receptor (α7nAChR) in insulin sensitivity improvement has already been shown in rodents both in vivo and in vitro. However, no data are available on α7nAChR expression in human adipocytes. OBJECTIVE: To investigate the expression and protein content of α7nAChR in human subcutaneous adipose tissue (SAT) and in isolated mature adipocytes. DESIGN: A total of 39 SAT biopsy specimens obtained from obese and normal-weight subjects were used to assess α7nAChR messenger RNA levels and to stimulate α7nAChR with a specific agonist and antagonist in vitro. Additional SATs from eight non-diabetic obese subjects were also studied, before and after a 3-month lifestyle intervention. RESULTS: α7nAChR expression was significantly lower in the SAT of obese subjects compared with that of normal-weight subjects. In mature adipocytes isolated from morbidly obese subjects (body mass index > 40 kg m(-2)), α7nAChR expression was 75% lower compared with adipocytes from normal-weight subjects. In adipocytes of obese subjects, α7nAChR was downregulated also at protein level. In eight non-diabetic obese subjects, a lifestyle intervention (3 months of diet and physical activity) induced a significant weight loss and an increase in α7nAChR SAT expression. In vitro stimulation of adipocytes with the specific α7nAChR agonist PNU282987 induced a significant anti-inflammatory effect. Furthermore, a similar downregulation of the inflammatory profile, associated with a significant increase in α7nAChR protein level, was observed after genistein stimulation. CONCLUSIONS: These results provide evidence that α7nAChR expression levels are significantly decreased in obese subjects, and that this receptor modulates inflammatory gene expression in human adipocytes. The upregulation of α7nAChR by genistein stimulation opens new insights for the management of low-grade inflammation linked to human obesity.

Sagittal abdominal diameter is more predictive of cardiovascular risk than abdominal fat compartments in severe obesity.

OBJECTIVE: To compare the predictive role of abdominal fat distribution by computed tomography (CT) with that of total abdominal fat by sagittal abdominal diameter (SAD) on cardiovascular risk in severe obesity. DESIGN: A cross-sectional, clinical study. SUBJECTS: 64 males and 64 females, aged 42+/-15 years (mean+/-s.d.; range 18-75 years), BMI (kg/m(2)) 41.7+/-5.3 (30.2-57.6). MEASUREMENTS: Blood glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides (TGLs), insulin (IRI), insulin resistance (HOMA-IR), slice areas (cm(2)) of total (tSAT), superficial (sSAT) and deep subcutaneous adipose tissue (dSAT), visceral adipose tissue (VAT) and SAD (mm) by CT. RESULTS: The sSAT depot was negatively associated with blood glucose, HOMA-IR, LDL cholesterol and TGLs, whereas dSAT was negatively associated with HDL cholesterol. VAT was associated with blood glucose and HOMA-IR, whereas SAD was associated with all variables evaluated. In males, VAT was associated with blood glucose (r(2)=0.12, P<0.01), SAD was associated with blood glucose (r(2)=0.67, P<0.01), IRI (r(2)=0.65, P<0.05), and HOMA-IR (r(2)=0.67, P<0.01). In females, sSAT was negatively associated with blood glucose (r(2)=0.63, P<0.05), whereas VAT was associated positively with blood glucose (r(2)=0.21, P< 0.001), total cholesterol (r(2)=0.16, P<0.01), LDL cholesterol (r(2)=0.20, P<0.001) and TGLs (r(2)=0.12, P<0.01). SAD was associated positively with IRI (r(2)=0.52, P<0.05), HOMA-IR (r(2)=0.53, P<0.05), total cholesterol (r(2)=0.52, P<0.05), LDL cholesterol (r(2)=0.54, P<0.01), TGLs (r(2)=0.52, P<0.05) and negatively to HDL cholesterol (r(2)=0.51, P<0.001). CONCLUSION: When compared with CT-based measures of abdominal fat compartments, SAD is a more predictive indicator of cardiovascular risk in severe obesity.

Heart rate behavior during an exercise stress test in obese patients.

BACKGROUND AND AIMS: Heart rate (HR) response to exercise has not been fully described in the obese. We wanted to study the differences between obese and non-obese patients in HR behavior during an exercise stress test and to determine whether these differences influence exercise capacity. METHODS AND RESULTS: We studied 554 patients (318 females) who underwent a treadmill exercise test. All subjects were in sinus rhythm. Patients with ischemic heart disease, with reduced ejection fraction and patients taking drugs that interfere with HR were excluded. The population included 231 patients with BMI<30 kg/m(2) (group 1), 212 patients who were unfit and obese (group 2) and 111 patients who were trained obese (group 3). Resting HR was similar in the various groups. Peak HR, HR recovery and chronotropic index were lower in obese subjects, regardless of their fitness level. Multivariate analysis showed that HR related variables were associated with age, BMI, height, hypertension and various pharmacologic treatments, while exercise capacity was strongly dependent on HR behavior, as well as on sex, age, BMI and diabetes. CONCLUSION: Obese subjects have a marked impairment of HR behavior during exercise and in the recovery period, and the blunted increase in HR is the most important factor that influences exercise capacity.

Growth hormone therapy improves exercise capacity in adult patients with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is associated with an inappropriate proportion of fat mass (FM) to non-FM compared to simple obesity. Altered body composition in PWS resembles that seen in subjects with GH deficiency, in which a reduction of lean body mass (LBM) is observed. The low LBM may contribute to the reduced motor skills seen in PWS patients. AIM: The objective of the study was to investigate the effects of GH therapy on exercise capacity and body composition in a group of adult subjects with PWS. SUBJECTS AND METHODS: Twelve PWS adults (7 males and 5 females, aged 26.4+/-4.4 yr, body mass index 44.3+/-4.6 kg/m2) participated in the study. Body composition analysis and exercise stress test were carried out throughout the 12 months GH therapy. Body composition was measured by Dual Energy X-ray Absorptiometry. Physical performance was evaluated using treadmill exercise test. Exercise intensity was expressed as metabolic equivalents (MET, 1 MET= 3.5 ml O2 kg(-1) min(-1)). Statistical analysis was performed by repeated-measures analysis of variance followed by post-hoc analysis with t test for paired data for comparisons among the different follow ups. RESULTS: Compared to baseline GH therapy increased LBM at 6 (p<0.0001) and 12 months (p<0.005) (45.3+/-7.7 kg vs 48.6+/-6.7 kg vs 48.2+/-7.5 kg). FM% was significantly reduced both after 6 and 12 months (p<0.02) (56.1+/-4.8% vs 53.7+/-4.2% vs 53.3+/-4.8%). Attained MET were found to be improved by 16% after 6 months and by 19% after 12 months of GH (p<0.001), while the small further rise between 6 and 12 months was not significant. CONCLUSIONS: Our findings seem to support the view that GH therapy has beneficial effects on physical activity and agility as well as on body composition of adult patients with PWS.

Rosiglitazone is more effective than metformin in improving fasting indexes of glucose metabolism in severely obese, non-diabetic patients.

AIM: In obese patients, the diet-induced weight loss markedly improves glucose tolerance with an increase in insulin sensitivity and a partial reduction of insulin secretion. The association with metformin treatment might potentiate the effect of diet alone. METHODS: From patients admitted to our Nutritional Division for diet programme, we selected obese, non-diabetic, uncomplicated patients with age 18-65 years and body mass index 35-50 kg/m(2) and studied the effects of a 6-month pharmacological treatment with either metformin (850 mg twice daily) or rosiglitazone (4 mg twice daily) on possible changes in body weight, fat mass, glucose and lipids metabolism. RESULTS: A significant weight loss and reduction of fat mass was demonstrated with metformin (-9.7 +/- 1.8 kg and -6.6 +/- 1.1 kg) and also with rosiglitazone (-11.0 +/- 1.9 kg and -7.2 +/- 1.8 kg), without fluid retention in either treatment group. Rosiglitazone administration induced a significant decrease in glucose concentration (4.7 +/- 0.1 vs. 4.4 +/- 0.1 mmol/l, p < 0.005) and insulin-circulating level (13.6 +/- 1.5 vs. 8.0 +/- 0.,7 microU/ml, p < 0.005), an increase in insulin sensitivity as measured by homeostatic model assessment (HOMA) of insulin sensitivity (68.9 +/- 8.8 vs. 109.9 +/- 10.3, p < 0.005) with a concomitant decrease in beta-cell function as measured by HOMA of beta-cell function (163.2 +/- 16.1 vs. 127.4 +/- 8.4, p < 0.005). In contrast, metformin did not produce any significant effect on blood glucose concentration, insulin level and HOMA2 indexes. No adverse events were registered with pharmacological treatments. CONCLUSION: Our study shows that in severely obese, non-diabetic, hyperinsulinaemic patients undergoing a nutritional programme, rosiglitazone is more effective than metformin in producing favourable changes in fasting-based indexes of glucose metabolism, with a reduction of both insulin resistance and hyperinsulinaemia. In spite of previous studies reporting rosiglitazone-induced body weight gain, in our study the joint treatment with diet and rosiglitazone was accompanied by weight loss and fat mass reduction.

Lack of association between the tetranucleotide repeat polymorphism in the 3'-flanking region of the leptin gene and hypertension in severely obese patients.

Conflicting data suggest an association between leptin gene polymorphisms and essential hypertension independently of obesity. The aim of this study was to evaluate, in severely obese subjects, the role of one of these polymorphic markers in relation to the development of hypertension. The study included 325 obese patients with mean body mass index (BMI) of 46+/-6.94 kg/m2. One hundred sixty-six were hypertensive and 159 normotensive. In both groups, the presence of a tetranucleotide repeat in the 3' flanking region of the Ob gene was investigated using polymerase chain reaction (PCR). Due to the genetic variant, in the region studied it is possible to distinguish two alleles with different size distribution: Class I (shorter one) and Class II (longer one). Class I and Class II allele frequencies were not significantly different in obese patients when analyzed according to the presence or absence of hypertension. The results presented herein do not support a significant association of this Ob gene polymorphism with hypertension. These findings are in contrast with that reported in other populations. However, we cannot rule out that different ethnicity and/or phenotypic variability might mask small effects.

Impairment of GH responsiveness to combined GH-releasing hormone and arginine administration in adult patients with Prader-Willi syndrome.

OBJECTIVE: It is unclear if poor health outcomes of adult patients with Prader-Willi syndrome (PWS) are influenced by GH deficiency (GHD). Few studies have been focused on PWS adults, but further information on the concomitant role of obesity on GH/IGF-I axis function is needed. The aim of our study was to investigate the prevalence of GHD in a large group of adult subjects with genetically confirmed PWS. DESIGN AND SUBJECTS: We studied the GH response to a combined administration of GHRH (1 microg/kg i.v. at 0 minutes) and arginine (ARG) (30 g i.v., infused from 0 to 30 minutes) as well as the baseline IGF-I levels, in a group of 44 PWS adults (18 males, 26 females) aged 18-41.1 years. The same protocol was carried out in a control group of 17 obese subjects (7 males, 10 females) aged 21.8-45.8 years. MEASUREMENTS: Blood samples were taken at -15 and 0 minutes and then 30, 45, 60, 90 and 120 minutes after GHRH administration. Serum GH and total IGF-I concentrations were measured by chemioluminescence. Statistical analysis was performed by Student's t-test for unpaired data, and using analysis of variance for parametric and nonparametric (Mann-Whitney test) data, where appropriate. The relationship between pairs of variables was assessed by Pearson's correlation. Independent variables influencing GH secretion were tested by multiple linear regression analysis. RESULTS: The GH response to GHRH + ARG was significantly lower in PWS patients (GH peak (mean +/- SE) 8.4 +/- 1.2 microg/l; AUC: 471.4 +/- 77.8 microg/l/h) than obese subjects (GH peak 15.7 +/- 2.9 microg/l, P < 0.02; AUC 956 +/- 182.9 microg/l/h, P < 0.005). When considered individually, 17 of 44 PWS individuals (38.6%) were severely GHD, according to the cut-off limit of 4.1 microg/l for obese individuals, and low IGF-I-values were present in 33 PWS patients. Moreover, impaired GH response was combined with subnormal IGF-I levels in all PWS patients with GHD. CONCLUSIONS: Adult subjects with PWS had a reduced responsiveness to GHRH + ARG administration associated with reduced IGF-I levels. In addition, a severe GHD for age was demonstrated in a significant percentage of PWS subjects. These findings are in agreement with the hypothesis that a complex derangement of hypothalamus-pituitary axis occurred in PWS, and suggested that impaired GH secretion is not an artefact of obesity.

Predictors of postabsorptive ghrelin secretion after intake of different macronutrients.

CONTEXT: Release of ghrelin, a gastrointestinal hormone regulating feeding and energy balance, is blunted in obesity, a condition associated with insulin resistance. OBJECTIVE: The objective was to identify anthropometric and metabolic predictors of postabsorptive ghrelin secretion. DESIGN: We evaluated ghrelin, insulin, glucose, and leptin secretion overnight and after intake of different macronutrients. SUBJECTS: Ten obese subjects (age, 31.8 +/- 2.5 yr; body mass index, 43.4 +/- 0.8 kg/m(2)) and six lean subjects (age, 33.5 +/- 2.4 yr; body mass index, 21.8 +/- 1.4 kg/m(2)) participated in the study. MAIN OUTCOME MEASURES: The main outcome measures were resting energy expenditure (REE); fat mass; nighttime approximate entropy (ApEn) and synchronicity (cross-ApEn) of ghrelin, insulin, and leptin; insulin sensitivity by homeostatic model approach insulin-sensitivity (HOMA-S%); postabsorptive area under the curve (AUC); and Delta of ghrelin, insulin, glucose, and leptin after carbohydrate-, lipid-, and protein-rich test meals. RESULTS: Nighttime ApEn scores were higher in obese than lean subjects (P < 0.01). Cross-ApEn revealed a synchronicity between ghrelin-insulin, ghrelin-leptin, and insulin-leptin in both groups. Compared with baseline, ghrelin decreased significantly (P < 0.01) in lean and obese subjects after carbohydrates (42.2 vs. 28.5%; P < 0.05), lipids (40.2 vs. 26.2%; P < 0.01), and proteins (42.2 vs. 26.3%; P < 0.01) devoid of between-meal ghrelin differences. Significant associations occurred between nocturnal ghrelin ApEn and insulin (r = 0.53; P < 0.05), postmeal ghrelin AUCs and REE (r = -0.57; P < 0.05), and HOMA-S% (r = 0.52; P < 0.05), postmeal ghrelin Delta and HOMA-S% (r = 0.60; P < 0.05). REE (beta = -0.57; P = 0.02) and ghrelin ApEn (beta = -0.62; P = 0.01) were predictors of postmeal ghrelin AUC and Delta, respectively. CONCLUSIONS: Obesity determined a decreased orderliness of ghrelin secretion and a relative loss of ghrelin-insulin synchrony. Postabsorptive ghrelin secretion decreased significantly both in obese and lean subjects, was related to insulin sensitivity, and was predicted by energy expenditure and hormone pulsatility.

A simple tool to predict exercise capacity of obese patients with ischaemic heart disease.

OBJECTIVE: To define an equation that predicts exercise capacity taking into account body mass index (BMI). DESIGN: Retrospective analysis and validation study of a multidisciplinary programme aimed at weight loss and physical rehabilitation. SETTING: Tertiary referral hospital. PATIENTS AND METHODS: 372 consecutive obese participants (249 men) with stable ischaemic heart disease, aged mean 60.1 (SD 8.7) years, underwent a treadmill exercise test. BMI was 37.8 (4.5) kg/m(2). In the validation study the model was tested in 87 patients with similar characteristics. RESULTS: Mean exercise intensity was 6.6 (SD 2.4) metabolic equivalents (METs). Multivariate linear regression analysis defined two simple models that considered exercise intensity as the dependent variable and a set of independent variables such as anthropometric measures, age and sex in the first one, plus associated clinical conditions and drug treatment in the second one. The correlation coefficients of the two models were R = 0.630 and R = 0.677, respectively. Age, BMI and sex were the strongest predictors of exercise capacity. The first derived equation efficiently predicted exercise capacity: in the validation study predicted exercise intensity was 6.3 (1.6) METs and attained exercise intensity was 6.3 (2.4) METs (p = 0.903) with a highly significant correlation (R = 0.534, p < 0.001). CONCLUSION: BMI is an important determinant of exercise capacity of obese people with ischaemic heart disease. The use of a simple equation may help in predicting exercise capacity, in individualising exercise protocol and in setting up rehabilitation programs for obese patients.

Abdominal fat index by ultrasound does not estimate the metabolic risk factors of cardiovascular disease better than waist circumference in severe obesity.

OBJECTIVE: To evaluate by ultrasound the ratio between preperitoneal (P) and subcutaneous (S) fat (AFI), in quantifying the cardiovascular risk in 258 obese patients (BMI 41.2+/-6.3 kg/m2; age 45.1 +/- 13.6 years). RESEARCH METHODS AND PROCEDURES: Glucose, insulin, lipid profile, uric acid and fibrinogen were measured. HOMA-IR, waist girth, AFI and quartiles of BMI were calculated. RESULTS: AFI lowered with increasing BMI and showed a positive correlation with TGL (r=0.37, P<0.01) and uric acid (r=0.40, P<0.001) in the 1st quartile of BMI (30.2-36.4) and a negative correlation with HDL (r=- 0.32, P<0.001) in the 3rd quartile (40.6-45.1). When BMI exceeded the value of 45.2 kg/m2 these correlations were no longer significant. In all subjects S correlated positively with uric acid (r=0.64, P<0.001), and negatively with HOMA-IR (r=- 0.41, P<0.001) and TGL (r=- 0.35, P=0.02); P correlated positively with CHOL (r=0.48, P=0.04) and TGL (r=0.33, P=0.03), and negatively with HDL (r=- 0.46, P=0.03). Waist girth showed more significant correlations than AFI in the lower quartiles of BMI, but not at the highest one. DISCUSSION: AFI, P and S, as waist girth do not seem to quantify the metabolic risk factors of cardiovascular disease in severe obese subjects, but AFI is probably useful in obese populations with BMI<45 kg/m2, even though not as strong as waist girth.

Paraoxonase activity in high-density lipoproteins: a comparison between healthy and obese females.

Paraoxonase, an enzyme associated with high-density lipoprotein (HDL-PON), exerts a protective effect against oxidative damage of circulating cells and lipoproteins, modulates the susceptibility of HDL to atherogenic modifications such as glycation and homocysteinylation, and even exerts an antiinflammatory role. The aim of the present study was to investigate the relationship between lipoprotein oxidative stress and the activity of HDL-PON in healthy and obese subjects. Therefore, the activity of HDL-PON and the levels of lipid hydroperoxides in HDL and low-density lipoprotein (LDL) isolated from plasma of obese females (n = 12) and age-sex-matched controls (n = 31) were compared. Our results demonstrated for the first time that the activity of HDL-PON in obese subjects was significantly lower compared with that in controls (P < 0.001). Moreover, our results showed a significant increase in the levels of lipid hydroperoxides in HDL and LDL isolated from obese subjects (P < 0.001). The negative correlations established between HDL-PON activity and the levels of lipid hydroperoxides associated with HDL and LDL confirm the relationship between paraoxonase activity and lipid peroxidation of lipoproteins. Plasma levels of leptin correlated negatively with HDL-PON activity and positively with levels of lipid hydroperoxides in HDL and LDL of obese subjects, suggesting a relationship between leptin and oxidative damage of lipoproteins. In conclusion, our study demonstrated that the increase in oxidative stress in LDL and HDL of obese subjects is associated with a decrease in HDL-PON activity. The lower paraoxonase activity and the compositional changes in HDL and LDL could contribute to the greater risk of cardiovascular disease associated with obesity.

Weight cycling and cardiovascular risk factors in obesity.

OBJECTIVE: To assess the relationship between weight cycling and some cardiovascular risk factors in a wide sample of obese subjects. DESIGN: Cross-sectional study with retrospective evaluation of weight and dieting history. SUBJECTS: In all, 459 obese subjects, 340 women and 119 men (age: 19-65 y; BMI: 30-69 kg/m2). MEASUREMENTS: Body composition and fat distribution (by bioelectrical impedance analysis and anthropometry), systolic and diastolic blood pressure, plasma glucose, total and HDL cholesterol, triglycerides, insulin and insulin resistance by HOMAir, various weight cycling indices. RESULTS: A positive correlation between weight cycling indices, BMI and percent body fat was found in both genders. Also, the maximum absolute amount of weight regained following a single diet episode was significantly associated to insulin and HOMAir in both genders. However, these correlations disappeared when the data were controlled for age and BMI. CONCLUSION: In obese subjects of both genders weight cycling, and in particular weight regain, does not appear to be associated with adverse effects on body composition, fat distribution or cardiovascular risk factors in an independent manner, but rather in relation to fat accumulation over years.

Effect of chronic treatment with beta-blockers on resting energy expenditure in obese hypertensive patients during a low-calorie and physical training program.

BACKGROUND AND AIM: To evaluate whether chronic treatment with beta-blockers influences resting energy expenditure (REE) and weight loss after a period of diet and physical activity in obese hypertensive patients. METHODS AND RESULTS: Seventy-eight obese hypertensive patients (24 males and 54 females) aged 53.7 +/- 11.1 years with mean BMI of 42.4 +/- 5.8 kg/m2 were enrolled. Thirty-eight patients were using beta-blockers while 40 patients who had not received beta-blockers in the past 6 months were the control group. REE was measured with indirect calorimetric method. Total body fat mass, total body fat-free mass (FFM) and total body water (W) were determined by bioelectrical impedance analysis. Patients and controls underwent a structured physical training program and a hypocaloric diet for a period of 31.6 +/- 10.6 days. Measured REE in patients taking beta-blockers was 1818 +/- 309 kcal/24 h and 1853 +/- 348 kcal/24 h in patients not taking beta-blockers; p = non significant. Weight and BMI loss were similar between the two groups and were respectively -6.43 +/- 2.62 kg and -2.42 +/- 0.91 kg/m2 in the beta-blocker group and -7.49 +/- 3.10 kg, -2.78 +/- 1.03 kg/m2 in the non beta-blocker group. Body composition was similar in the two groups. In the comparison between patients treated with selective beta 1-adrenoceptors blockers and non selective beta-blockers we found a significant difference in REE (1704 +/- 283 vs 1974 +/- 278; p = 0.012) and in weight loss (-5.6 +/- 2.4 vs -7.5 +/- 2.7; p = 0.048) at the end of study. CONCLUSIONS: Beta-blockers are not associated with a lower REE in obese subjects compared to other antihypertensive treatment. Use of non selective beta-adrenergic blockers is associated with a higher REE and weight loss compared to use of selective beta 1-adrenergic blockers. Non selective beta-blockers could be indicated among first choice drugs in hypertensive severely obese subjects without contraindications to beta-blockade.

Feasibility of air plethysmography (BOD POD) in morbid obesity: a pilot study.

The assessment of body composition (BC) in morbidly obese patients is a difficult procedure. Air-displacement plethysmography (ADP), which measures body density, is a very promising technique for BC assessment in health and disease. However, there are very few data about the feasibility of applying ADP on morbidly obese patients, which theoretically could be affected by large body size and difficulty in lung volume measurements. The main aim of this pilot study was to evaluate the feasibility of using ADP for BC assessment in morbidly obese patients. We studied nine subjects (6 males and 3 females) who had a mean age (+/-SD) of 47.0+/-13.5 years and body mass index (BMI) of 46.6+/-7.7 kg/m(2) (range 36.4-58.8). All patients could fit into the instrument chamber and perform the manoeuvre for pulmonary plethysmography. Mean lung volume was 3.9+/-1.2 l and mean percent body fat was 53.1+/-6.6 (range 46.0-67.5). These results indicate that ADP appears to be suitable for patients with BMI over 40 kg/m(2) and produces realistic BC data.

PRL-secreting pituitary adenomas in pregnancy.

Dopamine-agonists have significantly increased the number of pregnancies in women with micro- and macro-prolactinomas, as ovulation can be restored in the great majority of these patients. Thus, the main questions regard the possible consequences of high estrogen levels on tumor volume and the possible effects of D2-agonists on fetal development. While the risk of tumor increase is low in patients with prolactin secreting micro-adenoma (MIP), in PRL secreting macro-adenoma (MAP) patients the possibility of tumor growth is enhanced and influenced by previous treatment. Moreover, while it is well known that the exposition for only the first 4 weeks to bromocriptine (BRC) therapy does not affect the outcome of pregnancy, data on the use of BRC during the whole gestation are limited to just over 100 cases. Female pregnant patients with MIP, therefore, must be reassured and medical therapy suspended, with successive clinical follow-up. In the case of pregnant MAP subjects, the best approach from pre-pregnancy debulking, dopamine-agonist therapy interruption and BRC therapy continuation must be agreed on with the patient, and a careful follow-up instituted.

Lack of association between UCP2 gene polymorphisms and obesity phenotype in Italian Caucasians.

The importance of the genetic component on adipose tissue accumulation has been clearly demonstrated. Among the candidate genes investigated, there are those that regulate thermogenesis and, thus, can affect energy expenditure. The uncoupling proteins (UCPs) are a family of proteins that uncouple respiration leading to generation of heat and increased energy expenditure. Contradictory data indicate that allelic variants in their coding genes might be associated with obesity. In this study we evaluated the role of two allelic variants of the UCP2 gene in obesity and the association with its sub-phenotypic characteristics. To this aim, 360 morbidly obese patients [age: 45 +/- 15 yr, body mass index (BMI): 46 +/- 7 kg/m2] and 103 normal weight subjects (BMI < 24 kg/m2) were genotyped for the 45 bais-pair (bp) insertion/deletion (I/D) in the 3'-untraslated region of exon 8 of the UCP2 gene while the presence of an Ala/Val substitution at codon 55 (Ala55Val) of the same gene was studied in 104 obese and 50 lean subjects. Patients also underwent a study protocol including measurements of BMI, waist-to-hip ratio (WHR), resting energy expenditure (REE), energy intake, fat mass (FM) and free fat mass (FFM), total cholesterol (TCH), high density lipoprotein (HDL) cholesterol, triacylglyceroles (TG), leptin levels, basal glucose, immunoreactive insulin (IRI), glycated haemoglobin (HbA1c), insulin sensitivity and thyroid hormones. No significant association between the two polymorphisms studied and the clinical, metabolic and anthropometric parameters characteristic of the obese phenotype was found. These results, in accordance with similar findings previously obtained in other ethnic groups, suggest that these two UCP2 allelic variants may not have a direct role in the pathogenesis and development of obesity.