The role of psychological well-being in obese and overweight older adults.

Being obese or overweight is often associated with impaired quality of life and psychological well-being (PWB) in comparison with normal-weight people (Giuli et al., 2014), both in developed and developing countries. PWB is considered a very important correlate of subjective well-being in people with excess weight. The concept of PWB is based on Ryff's multidimensional model (Ryff, 2014), which considers well-being as eudaemonic concept, and includes six dimensions: autonomy, environmental mastery, personal growth, positive relations with others, purpose in life, and self-acceptance. Few studies have analyzed the role of specific correlates of perceived well-being in the obese and overweight Italian older population. The purpose of this study was to evaluate the role of perceived well-being in obese and overweight older adults. Our study included 124 overweight and obese older participants, aged 60 years or more, selected from patients attending the Division of Endocrinology, Department of Clinical and Molecular Sciences of Polytechnic University of Marche (Italy). As previously described (Giuli et al., 2014), the participants were recruited on the basis of specific inclusion/exclusion criteria, in a period of three years (January 2010-December 2012).

Effects of in vitro supplementation with Syzygium cumini (L.) on platelets from subjects affected by diabetes mellitus.

The aim of this study was to assess the in vitro effects of Syzygium cumini (L.) (Sc) incubation on platelets from patients with diabetes, in order to test its efficacy as a potential adjuvant therapy. This study was performed on 77 patients with diabetes [29 in good (DMgc) and 48 in poor glycemic control (DMpc)] and 85 controls. In patients, platelets were analyzed at recruitment and after in vitro Sc incubation (final concentration of 200 µg/ml for 3 hours at 37 °C), whereas in controls only basal evaluation was performed. Lipoperoxide and nitric oxide (NO) levels, superoxide dismutase (SOD) and Na(+)/K(+) ATPase activities, total antioxidant capacity (TAC), and membrane fluidity tested by anisotropy of fluorescent probes 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) and 1-6-phenyl-1,3,5-hexatriene (DPH) were determined. Collagen-induced platelet aggregation was also evaluated. In vitro Sc activity counteracts oxidative damage, by improving platelet function through augmented membrane fluidity and Na(+)/K(+) ATPase activity; it also enhances antioxidant system functionality by increasing NO levels, SOD activity, and TAC and by decreasing lipoperoxide levels both in whole samples and in DMgc and DMpc. In addition, a slight tendency towards collagen-induced platelet aggregation decrease after Sc was observed. However, all these parameters, even after improvement, did not reach the levels of control subjects. Our results suggest that Sc may have a preventive and protective effect in oxidative damage progression associated with diabetes mellitus and its complications. If our data will be confirmed, Sc supplementation might become a further tool in the management of this disease, especially in view of its easy availability, safety, low cost, and absence of side effects.

Correlates of perceived health related quality of life in obese, overweight and normal weight older adults: an observational study.

BACKGROUND: Obesity is a complex multifactorial disease, which also has an impact on quality of life. The aim of this paper is to identify the correlates of perceived health related quality of life in obese, overweight and normal weight Italians older adults. METHODS: 205 subjects at the age ≥ 60 yrs. were recruited into the Division of Endocrinology of the Polytechnic University of Marche Region, Ancona (Italy). A protocol of questionnaires was constructed for data collection, and included domains such as physical activity, quality of life, socio-psychological aspects. The association of the latter variables with SF-36 Health Survey physical component (PCS-36) were evaluated in the whole sample. Multiple linear regression models were used to assess the effect of independent variables on PCS-36 and the physical subscales of SF-36. RESULTS: PCS-36 showed a lower score in the obese and overweight subjects than the normal weight group (post-hoc test, p < 0.001 and p < 0.05 respectively). Age, gender (male), Body Mass Index, years of education, Physical Activity Scale for the Elderly (PASE) total score, Hospital Anxiety and Depression Scale anxiety, Hospital Anxiety and Depression Scale depression, number of medications prescribed and number of diseases were included in the model. Negative and significant PCS-associated variables included depression (p = 0.009), BMI (p = 0.001), age in years (p = 0.007), whereas positive and significant PCS-associated independent variables were years of education (p = 0.022), physical activity (p = 0.026). BMI was negatively associated with all the physical subscales of SF-36 (p < 0.05). CONCLUSIONS: Research funding should be invested in the study of the benefits accruing from reducing obesity in the elderly.

Elevated 1-hour postload plasma glucose levels identify subjects with normal glucose tolerance but impaired ß-cell function, insulin resistance, and worse cardiovascular risk profile: the GENFIEV study.

CONTEXT: In subjects with normal glucose tolerance (NGT) 1-hour postload plasma glucose (1-h oral glucose tolerance test [OGTT]) of >155 mg/dL predicts type 2 diabetes (T2DM) and is associated with subclinical atherosclerosis. OBJECTIVE: The purpose of this study was to evaluate ß-cell function, insulin resistance, and cardiovascular risk profile in subjects with NGT with a 1-h OGTT glucose of >155 mg/dL. PATIENTS AND METHODS: The GENFIEV (Genetics, PHYsiopathology, and Evolution of Type 2 diabetes) study is a multicenter study recruiting individuals at high risk of T2DM. A total of 926 subjects underwent a 75-g OGTT for assessment of plasma glucose and C-peptide for mathematical modeling of ß-cell function (derivative and proportional control). Fasting insulin, lipid profile, and clinical parameters were determined as well. RESULTS: A 1-hour OGTT glucose of >155 mg/dL was found in 39% of subjects with NGT, 76% with impaired fasting glucose (IFG), 90% with impaired glucose tolerance (IGT), and 99% and 98% with IFG + IGT or newly diagnosed T2DM, respectively. Among subjects with NGT (n = 474), those with 1-hour OGTT glucose of >155 mg/dL were more insulin-resistant and had worse ß-cell function than those with 1-hour OGTT glucose of ≤155 mg/dL. Moreover, glycosylated hemoglobin, blood pressure, low-density lipoprotein cholesterol, and triglycerides were higher in subjects with NGT with 1-hour OGTT glucose of >155 mg/dL, whereas high-density lipoprotein cholesterol was lower compared with that in subjects with NGT with 1-hour OGTT glucose of ≤155 mg/dL. Compared with subjects with IGT, those with NGT with 1-hour OGTT glucose of >155 mg/dL had comparable cardiovascular risk profile and insulin resistance but slightly better ß-cell function. CONCLUSIONS: Among subjects with NGT, those with 1-hour OGTT glucose of >155 mg/dL showed lower insulin sensitivity, impaired ß-cell function, and worse cardiovascular risk profile and therefore are at greater risk of developing T2DM and cardiovascular disease.

Pathogenetic mechanisms and cardiovascular risk: differences between HbA(1c) and oral glucose tolerance test for the diagnosis of glucose tolerance.

OBJECTIVE: To ascertain to which extent the use of HbA(1c) and oral glucose tolerance test (OGTT) for diagnosis of glucose tolerance could identify individuals with different pathogenetic mechanisms and cardiovascular risk profile. RESEARCH DESIGN AND METHODS: A total of 844 subjects (44% men; age 49.5 ± 11 years; BMI 29 ± 5 kg/m(2)) participated in this study. Parameters of ß-cell function were derived from deconvolution of the plasma C-peptide concentration after a 75-g OGTT and insulin sensitivity assessed by homeostasis model assessment of insulin resistance (IR). Cardiovascular risk profile was based on determination of plasma lipids and measurements of body weight, waist circumference, and blood pressure. Glucose regulation categories by OGTT and HbA(1c) were compared with respect to insulin action, insulin secretion, and cardiovascular risk profile. RESULTS: OGTT results showed 42% of the subjects had prediabetes and 15% had type 2 diabetes mellitus (T2DM), whereas the corresponding figures based on HbA(1c) were 38 and 11%, with a respective concordance rate of 54 and 44%. Subjects meeting both diagnostic criteria for prediabetes presented greater IR and impairment of insulin secretion and had a worse cardiovascular risk profile than those with normal glucose tolerance at both diagnostic methods. In a logistic regression analyses adjusted for age, sex, and BMI, prediabetic subjects, and even more T2DM subjects by OGTT, had greater chance to have IR and impaired insulin secretion. CONCLUSIONS: HbA(1c) identifies a smaller proportion of prediabetic individuals and even a smaller proportion of T2DM individuals than OGTT, with no difference in IR, insulin secretion, and cardiovascular risk profile. Subjects fulfilling both diagnostic methods for prediabetes or T2DM are characterized by a worse metabolic profile.

Corticotrophin-releasing hormone and desmopressin tests in the differential diagnosis between Cushing's disease and pseudo-Cushing state: a comparative study.

BACKGROUND: We recently proposed a new and effective way of interpreting human corticotrophin-releasing hormone (hCRH) and desmopressin (DDAVP) tests, for the differential diagnosis between Cushing's disease (CD) and pseudo-Cushing state (PC), based on the simultaneous analysis of ACTH and cortisol. OBJECTIVE: The study had the aims of comparing the diagnostic performance of the two tests and determining whether carrying out both tests was more beneficial than carrying out only one. PATIENTS AND MEASUREMENTS: We studied 30 CD, 18 PC and 12 control (CT) subjects: in these patients, hCRH test, DDAVP test, 24-h urinary free cortisol, serum cortisol after overnight 1-mg dexamethasone suppression test and serum cortisol circadian rhythm were performed. RESULTS: The hCRH test and the DDAVP test showed an identical and excellent diagnostic performance (sensitivity 96·6% and specificity 100% for both tests); moreover, the hCRH and DDAVP tests showed almost perfect diagnostic agreement (κ = 0·93; P < 0·05) with a significantly higher number of concordant diagnoses (58 cases of 60) than those resulting from all other possible combinations among the studied tests. Interestingly, there were no subjects in whom both hCRH and DDAVP tests gave a simultaneous misdiagnosis. CONCLUSIONS: Our study indicates that the hCRH and DDAVP tests have similar diagnostic performance and present excellent agreement, without giving simultaneous misdiagnosis in any subject. Because of these characteristics, the use of both tests offers the physician a valuable tool for those cases of hypercortisolism which are difficult to interpret.

Use of the desmopressin test in the differential diagnosis of pseudo-Cushing state from Cushing's disease.

CONTEXT: The desmopressin (DDAVP) test has been proposed to discriminate Cushing's disease (CD) from pseudo-Cushing states (PC); however, current information on its value is scarce and contradictory. OBJECTIVE: The aim of the study was to assess the ability of the DDAVP test in distinguishing between these conditions, with emphasis on subjects with mild hypercortisolism. DESIGN AND SETTING: We conducted a retrospective/prospective study at the Division of Endocrinology, Polytechnic University of Marche, Ancona, Italy. PATIENTS: The study included 52 subjects with CD, 28 with PC, and 31 control subjects (CT). INTERVENTION(S): We performed the DDAVP test and standard diagnostic procedures for the diagnosis of Cushing's syndrome. MAIN OUTCOME MEASURE(S): The diagnosis/exclusion of CD was measured. RESULTS: Interpretation of the DDAVP test based on percentage and absolute increment of cortisol and ACTH did not afford acceptable values of both sensitivity (SE) and specificity (SP). CD diagnosis based on simultaneous positivity for basal serum cortisol greater than 331 nmol/liter and absolute ACTH increment greater than 4 pmol/liter and its exclusion in subjects negative for one or both measures yielded an SE of 90.3% and an SP of 91.5%. The approach was also highly effective in distinguishing PC from: 1) CD with moderate values of urinary free cortisol (SE, 86.9%; SP, 92.8%); 2) CD with moderate values of serum cortisol after dexamethasone suppression (SE, 86.6%; SP, 92.8%); and 3) CD with moderate values of midnight serum cortisol (SE, 100%; SP, 92.8%). CONCLUSIONS: Interpretation of the DDAVP test through a combination of parameters allowed effective discrimination of CD from PC, even in subjects with mild hypercortisolism.

Anorexia nervosa: a role for L-arginine supplementation in cardiovascular risk factors?

OBJECTIVE: The aim of the present study was to evaluate the effects of a short-term oral L-arginine treatment on platelet NO production, intracellular calcium concentration, iNOS and eNOS expression, in AN patients. METHOD: Forty outpatients belonging to restricting subtype and 40 normal participants age and sex matched were enrolled in the study. RESULTS: NO production was significantly elevated in the platelets from AN patients compared with controls while [Ca(2+)](i) was significantly decreased in patients with respect to controls. Western blot analysis demonstrated that iNOS isoform was more pronounced in the cell lysates from AN patients than controls. After supplementation with L-arginine, both NO production and [Ca(2+)](i) seem to return to control levels, suggesting a probable recovery of their metabolisms. The same was found after western blot analysis of NOS expression. DISCUSSION: The results here proposed can be considered highly indicative of a positive effect of L-arginine supplementation on platelet NO production in AN patients.

Distinctive modulation of inflammatory and metabolic parameters in relation to zinc nutritional status in adult overweight/obese subjects.

Overweight and obesity are associated with low grade of inflammation and chronic inflammatory response characterized by abnormal production and activation of some pro-inflammatory signalling pathways. Taking into account that obesity is the direct result of an imbalance between energy intake and energy expenditure, the nutritional factors in the diet, with particular focus on zinc, may play a pivotal role in the development of obesity-associated comorbidities. Considering the potential interactions among zinc nutritional status, inflammation, overweight/obesity and insulin secretion, the aim of the present work was to clarify the influence of zinc dietary intake on some metabolic, inflammatory and zinc status parameters in adult overweight/obese subjects. We found a close interrelationship between nutritional zinc and obesity. In particular, subjects with a lower zinc dietary intake display a deeper inflammatory status, general impairment of the zinc status, an altered lipid profile and increased insulin production with respect to obese subjects with normal zinc dietary intake. Moreover, in the presence of low dietary zinc intake, the obese subjects are less capable to respond to oxidative stress and to inflammation leading to the development of obesity or to a worsening of already preexisting obesity status. In conclusion, a possible zinc supplementation in obese subjects with a deeper inflammatory status and more altered zinc profile may be suggested in order to limit or reduce the inflammation, taking also into account that zinc supplementation normalizes "inflammaging" as well as zinc profile leading to a correct intra- and extracellular zinc homeostasis.

Vascular endothelial growth factor and microvessel density in periodontitis patients with and without diabetes.

BACKGROUND: Periodontal disease is one of the major problems encountered in patients with diabetes mellitus (DM), and vascular changes may contribute to periodontitis. Our aim was to investigate vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) in patients with periodontitis with and without DM. METHODS: Immunohistochemical detection of VEGF and MVD analysis, evaluated by CD34+ endothelial cell counts, were performed in 66 gingival samples from patients with generalized, severe, chronic periodontitis who were divided into three groups: 22 participants without systemic diseases (controls), 22 participants with type 1 DM (T1DM), and 22 participants with type 2 DM (T2DM). RESULTS: In patients with T1DM or T2DM, positive VEGF cells were found to be significantly increased in the epithelium compared to controls. In patients with T1DM, endothelial VEGF expression and MVD were significantly greater than in patients with T2DM and controls. CONCLUSIONS: In patients with diabetes, VEGF overexpression plays a primary role in promoting the extravasation of inflammatory cells, suggesting a useful antiangiogenic strategy for periodontitis treatment. The decreased endothelial VEGF expression and MVD found in patients with T2DM may be caused by insulin resistance and endothelial dysfunction, which are often present in patients with T2DM.

Human corticotropin releasing hormone test performance in the differential diagnosis between Cushing's disease and pseudo-Cushing state is enhanced by combined ACTH and cortisol analysis.

OBJECTIVE: Corticotropin releasing hormone (CRH) test does not reliably distinguish Cushing's disease (CD) from normality or pseudo-Cushing state (PC). We assessed whether this could be achieved with a novel approach while preserving the ability of the test to distinguish CD from ectopic ACTH syndrome (EAS). Design Retrospective/prospective study. SUBJECTS AND METHODS: We studied 51 subjects with CD, 7 with EAS, 26 with PC, and 31 controls (CT). Human CRH (hCRH) test was performed at 0830 h by measuring plasma ACTH and serum cortisol at -15, 0, 15, 30, 45, 60, 90, and 120 min. RESULTS: The area under the curve-ACTH exhibited a significant negative correlation with baseline serum cortisol in CT and PC, but not in CD or EAS patients. ACTH response to hCRH was blunted in PC compared with CT, whereas peak serum cortisol was higher in PC than in CT subjects. These findings suggested that ACTH-dependent Cushing's syndrome can be diagnosed by the presence of two hCRH test parameters and excluded if either or both are absent. Application of i) basal serum cortisol >12 microg/dl and peak plasma ACTH >54 pg/ml, or ii) peak serum cortisol >21 microg/dl and peak plasma ACTH >45 pg/ml, had 91.3% (95% confidence intervals (CI) 81-97.1) and 94.8% (CI 85.6-98.9) sensitivity and 98.2% (CI 90.6-99.9) and 91.2% (CI 80.7-97) specificity respectively, in diagnosing ACTH-dependent Cushing's syndrome. The >14% serum cortisol increase from mean baseline values to the mean of 15 and 30 min values in patients who were positive for the test completely discriminated between CD and EAS. CONCLUSIONS: Simultaneous plasma ACTH and serum cortisol analysis enables the hCRH test to distinguish CD from PC and from normality, while preserving its ability to discriminate CD from EAS.

Interactions between lipoproteins and platelet membranes in obesity.

The aim was to investigate low-density lipoprotein (LDL) composition and Na(+)/K(+) adenosine triphosphatase (ATPase) and Ca(2+) ATPase activities and membrane fluidity measured by 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) in platelets from obese patients and controls in order to identify, if any, platelet membrane's chemical-physical and/or functional modifications associated with compositional modification of circulating lipoproteins. Moreover, we studied the in vitro effect on both platelet transmembrane cationic transport and fluidity, by incubating LDL from 30 obese subjects with platelets from 30 control subjects. The analysis of the chemical composition of LDL from obese patients showed a significant increase in the percent content of total cholesterol (TC) and triglycerides (TGs) and in the mean levels of lipid hydroperoxides compared to controls' LDL. Platelet Na(+)/K(+) ATPase and Ca(2+) ATPase activities showed, respectively, a significant decrease and increase in patients compared to controls; minor significant, respectively, decreases and increases are shown also in control platelets incubated with LDL from obese patients. Anisotropy tested with TMA-DPH probe was significantly increased both in platelets from obese patients and in control platelets incubated with LDL from obese patients compared to control platelets. This study highlights that obesity induces remarkable modifications both in lipoproteins and platelets. Both platelet hyperfunction and quantitative/qualitative alterations in plasma lipoproteins, as well as an altered interaction between circulating lipoproteins and platelets, might play a relevant role in the increased prevalence of the early atherosclerotic lesions development in obese subjects. The present data point out that obesity might represent a major potentially modifiable risk factor for the onset of numerous complications, in particular cardiovascular ones.

Protective effect of leg fat against cardiovascular risk factors in obese premenopausal women.

BACKGROUND AND AIMS: While the relationship between abdominal fat and cardiovascular risk (CVR) factors is well established, the possible protective role of peripheral fat against these factors has received less attention, particularly in severely obese individuals. The principal aim of this study was to analyse the relationship, if any, among amount of leg fat, CVR factors and body mass index (BMI) in obese premenopausal women. METHODS AND RESULTS: Subjects were 80 obese premenopausal women. Body composition was measured by dual energy X-ray absorptiometry (DEXA); CVR factors (blood pressure, plasma lipids, glucose) were determined and anthropometric measurements (waist and hip circumferences) taken. In severely obese women (BMI>40 kg/m(2)) leg fat correlated negatively with CVR factors, whereas metabolic parameters were not significantly different from those of subjects with BMI<40 kg/m(2). CONCLUSIONS: Leg fat seems to play a protective role against CVR factors in severely obese premenopausal women.

Metabolic syndrome does not increase angiographic restenosis rates after drug-eluting stent implantation.

Metabolic syndrome (MS) is associated with an increased risk of coronary heart disease, stroke, and cardiovascular mortality; but its effect on patients undergoing cardiac revascularization is still unclear. Robust evidence demonstrates that diabetes mellitus and insulin resistance are among the main risk factors for restenosis in patients requiring percutaneous myocardial revascularization. The recent advent of drug-eluting stents (DESs) has significantly reduced the incidence of restenosis compared with bare-metal stents, both in nondiabetic and in diabetic patients. The aim of the study was to evaluate the effect of MS on the risk of binary restenosis in DES implant recipients. One hundred eighty-nine recipients of successful DES implants performed between January and March 2005 for stable coronary artery disease underwent 1-year clinical and angiographic follow-up. Body mass index (BMI), blood pressure, fasting blood glucose, and lipid profile were determined. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria, with the waist criterion being substituted by a BMI>or=28.8 kg/m2. Metabolic and anthropometric information for MS diagnosis was available for 148 of 189 patients; 87 of 148 patients (58%) had MS. Patients with MS had higher BMI (28.4+/-3.8 vs 26+/-2.7 kg/m2, P<.0001), systolic blood pressure (133+/-14 vs 124+/-14 mm Hg, P=.0004), and fasting glucose (113+/-37 vs 92+/-17 mg/dL, P<.0001). They also had higher serum triglycerides (154+/-94 vs 113+/-43, P=.0018) and lower high-density lipoprotein cholesterol levels (39+/-9 vs 46+/-10, P<.0001). Rates of restenosis (10.5% vs 8.1%, P=not significant [NS]), target vessel revascularization (10.5% vs 11.3%, P=NS), and major adverse cardiac events (11.6% vs 14.5%, P=NS) were not significantly different in patients with MS compared with those without MS, nor was any association found between increased end point risk and presence of MS. When patients were subdivided into 6 subgroups by the presence of 0, 1, 2, 3, 4, or 5 of the MS components, restenosis rates were not significantly different among subgroups. In conclusion, MS is not associated with higher rates of restenosis, target vessel revascularization, or major adverse cardiac events; and no additional MS feature was associated with an increased risk.

Lipoproteins obtained from anorexia nervosa patients induce higher oxidative stress in U373MG astrocytes through nitric oxide production.

Eating disorders (ED) are a group of important psychiatric disorders that affect young men and women, and can have serious consequences. Among all ED, anorexia nervosa (AN) is the most typical but also the most severe. The pathogenesis of AN is multifactorial and a great variety of cognitive deficits may contribute to its pathogenesis. The present study is aimed to measure NO and peroxynitrite production, iNOS and nNOS expression by Western immunoblot after incubation of AN lipoproteins at different times with human astrocytoma cells. The AN-HDL treated cells showed an increased production of NO at 3 h versus control-HDL treated cells and a decreased production at 24 h. Regarding LDL, a significant increase of NO production was obtained both at 3 and 24 h. The AN-HDL and AN-LDL treated cells showed an increased production of peroxynitrite both at 3 and 24 h compared to control lipoproteins. Densitometric analysis of bands indicated that both iNOS and nNOS protein levels were significantly higher in the cells incubated with AN lipoproteins compared to cells incubated with control lipoproteins both at 3 and 24 h. Although the pathogenesis of AN remains uncertain, evidence exists that modifications to the lipoprotein profile and cholesterol, structural alterations of phospholipids and integral constituents of myelin and synaptosomes may be related to psychotic disorders and body image distortion common to AN. Thus, a relevant pathophysiological association between NO and depression is certainly a possibility, as well as a central role played by NO in the pathogenesis.

Changes in body composition and insulin sensitivity in severely obese subjects after laparoscopic adjustable silicone gastric banding (LASGB).

BACKGROUND: Laparoscopic adjustable silicone gastric banding (LASGB) is a viable therapeutic approach to achieve stable body weight reduction in severe obesity. The aim of this study was to evaluate body composition and metabolic features in morbidly obese patients before and after LASGB. MATERIAL/METHODS: There were 15 severely obese patients (Ob) (M/F: 4/11; mean age: 32.5 +/- 3.8 years) and 16 age-and sex-matched healthy lean controls (C) (M/F: 4/12; mean age: 39.5 +/- 2 years). Body mass index (BMI), waist circumference, waist-to-hip ratio, blood pressure, lipid profile, serum glucose and insulin during OGTT, and HOMA-IR were evaluated in all subjects. Body composition and fat distribution were measured using dual energy X-ray absorptiometry (DEXA). Patients were assessed before and six months after LASGB. RESULTS: The obese subjects showed several metabolic alterations. There were also positive correlations between waist, fat mass (FM), and HOMA-IR at baseline. After LASGB, mean BMI fell from 42.2 kg/m2 to 33.2 kg/m2; waist circumference and abdominal FM% decreased significantly. FM% declined, whereas FFM% increased. The ratio of FM loss to FFM loss was 3.7:1. Serum glucose and insulin levels during OGTT diminished slightly after weight loss and triglyceride levels fell dramatically. After LASGB, fasting insulin and HOMA-IR declined. RESULTS: LASGB induced a significant improvement in insulin sensitivity and a redistribution of body composition with a relative increase of FFM.

Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans.

Macrophage infiltration of white adipose tissue (WAT) is implicated in the metabolic complications of obesity. The precipitating event(s) and function(s) of macrophage infiltration into WAT are unknown. We demonstrate that >90% of all macrophages in WAT of obese mice and humans are localized to dead adipocytes, where they fuse to form syncytia that sequester and scavenge the residual "free" adipocyte lipid droplet and ultimately form multinucleate giant cells, a hallmark of chronic inflammation. Adipocyte death increases in obese (db/db) mice (30-fold) and humans and exhibits ultrastructural features of necrosis (but not apoptosis). These observations identify necrotic-like adipocyte death as a pathologic hallmark of obesity and suggest that scavenging of adipocyte debris is an important function of WAT macrophages in obese individuals. The frequency of adipocyte death is positively correlated with increased adipocyte size in obese mice and humans and in hormone-sensitive lipase-deficient (HSL-/-) mice, a model of adipocyte hypertrophy without increased adipose mass. WAT of HSL-/- mice exhibited a 15-fold increase in necrotic-like adipocyte death and formation of macrophage syncytia, coincident with increased tumor necrosis factor-alpha gene expression. These results provide a novel framework for understanding macrophage recruitment, function, and persistence in WAT of obese individuals.

Adipose tissue as an endocrine organ? A review of recent data related to cardiovascular complications of endocrine dysfunctions.

Clinical and experimental data obtained in the last few years have modified the concept of adipose tissue as one solely directed at energy storage and release. The adipose tissue is a target organ for glucocorticoids and several studies have been carried out on the function of hypothalamic-pituitary-adrenal axis in obese subjects without conclusive results. A recent and innovative finding is that adipose tissue can produce cortisol from its inactive precursor, cortisone. The identification of leptin, a hormone synthesised by fat tissue, has ushered in the modern view of this tissue as a true endocrine organ. Leptin is produced primarily by subcutaneous and to a lesser extent by visceral adipose tissue, and has a central role in controlling body weight and, especially in regulating fat stores. Leptin is also involved in several complex functions, including physiological processes associated with puberty. Another hormone of fat tissue is angiotensinogen, which is produced in larger amounts by visceral than subcutaneous fat. Human and animals adipose tissue express a whole renin-angiotensin system (RAS). Angiotensin II, the final effector of this system is probably produced locally by adipose tissue. The function of adipose RAS is not well known. RAS can participate together with other hormones and substances, in adipocyte differentiation and fat tissue growth, but could be also involved in the pathogenesis of complications of obesity including arterial hypertension.

Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal and overweight subjects.

To evaluate the expression of the renin-angiotensin system (RAS) genes in visceral (VAT) and subcutaneous adipose tissue (SAT) in normotensive subjects with different body mass index (BMI). Adipose tissue was obtained from 22 normotensive (12 normal weight and 10 overweight) patients during surgery for colecystectomy. Angiotensinogen (AGT), angiotensin II receptor type 1 (AT1), angiotensin converting enzyme (ACE) mRNA, and protein levels were measured by reverse transcriptase-polymerase chain reaction and Western blot analysis, respectively. The AGT mRNA and AT1 receptor mRNA levels were significantly higher in VAT than in SAT; AGT mRNA levels were higher, although not significantly, in overweight subjects in both SAT and VAT. There was no significant difference in ACE gene expression in the two tissues, and no expression of angiotensin II receptor type 2 (AT2). Finally, we failed to find mRNA for the renin gene in adipose tissue. The presence of AGT and ATI receptor in SAT and VAT was confirmed by Western blot analysis. Our study demonstrates the presence--and different levels of expression--of the various components of the RAS system (AGT, ATI, and ACE) in human SAT and VAT, and highlights the different role and regulation of the system in the two tissues. Its high expression in VAT suggests that its regulation and function are involved in all conditions where visceral adiposity is present.