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Summary Background Bariatric surgery is a treatment option for patients with severe obesity and improves parameters of cardiovascular and/or metabolic disease. Carotid intima media thickness (C-IMT) is a surrogate measure of subclinical atherosclerosis. Previous studies showed short to mid-term arrest and even regression of C‑IMT progression following bariatric surgery. We aimed to investigate the long-term effect of weight loss on C‑IMT progression 10 years after bariatric surgery in comparison to a population-based control cohort. Methods In total, 21 eligible patients were examined preoperatively, at 5 and 10 years after bariatric surgery. Anthropometric parameters, plasma triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), insulin, and glucose were assessed at all three study visits. C‑IMT was measured via B‑mode scans of the common carotid artery. C‑IMT progression was measured in an age-matched and BMI-matched cohort selected from the population-based Bruneck study to compare with changes in C‑IMT progression after bariatric surgery. Results C‑IMT remained stable over the 10-year observation period after bariatric surgery. The control cohort showed a significant C‑IMT progression over 10 years. The difference in C‑IMT progression over 10 years was significant (p Conclusion Weight loss induced by bariatric surgery halts the natural progression of C‑IMT over a 10-year observation period.

BACKGROUND: Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. This disorder is associated with genetic variants that result in virtually absent (null-null) or impaired (non-null) LDL-receptor activity. Loss-of-function variants in the gene encoding angiopoietin-like 3 (ANGPTL3) are associated with hypolipidemia and protection against atherosclerotic cardiovascular disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) every 4 weeks or placebo. The primary outcome was the percent change from baseline in the LDL cholesterol level at week 24. RESULTS: The mean baseline LDL cholesterol level in the two groups was 255.1 mg per deciliter, despite the receipt of maximum doses of background lipid-lowering therapy. At week 24, patients in the evinacumab group had a relative reduction from baseline in the LDL cholesterol level of 47.1%, as compared with an increase of 1.9% in the placebo group, for a between-group least-squares mean difference of -49.0 percentage points (95% confidence interval [CI], -65.0 to -33.1; P

Background and aims Wnt signaling is involved in atherosclerotic plaque formation directly and indirectly by modulating cardiovascular risk factors. We investigated whether circulating concentrations of Wnt inhibitors are associated with cardiovascular events in subjects with intermediate cardiovascular risk. Methods 904 non-diabetic subjects participating in the SAPHIR study were assessed. In the SAPHIR study, middle-aged women without overt atherosclerotic disease at study entry were followed up for 10 years. 88 patients of our study cohort developed cardiovascular disease at follow-up (CVD group). Subjects of the CVD group were 1:2 case-control matched for age, sex, BMI and smoking behavior with subjects without overt cardiovascular disease after a 10 year-follow-up (control group). 18 patients of the CVD group and 19 subjects of the control group were retrospectively excluded due to fulfilling exclusion criteria. Baseline circulating sclerostin, dickkopf (DKK)-1, secreted frizzled-related protein (SFRP)-1 and Wnt inhibitory factor (WIF)-1 levels were assessed by ELISA. Results Baseline systemic SFRP-1 and WIF-1 levels were significantly higher in patients with cardiovascular events (n = 70) when compared to healthy controls (n = 157) while DKK-1 and sclerostin levels were similar in both groups. Logistic regression analysis revealed WIF-1 as a significant predictor of future cardiovascular events. Conclusions Our data suggest that increased SFRP-1 and WIF-1 levels precede the development of symptomatic atherosclerotic disease. Assessment of systemic WIF-1 levels, which turned out to be independently associated with CVD, might help to early identify patients at intermediate cardiovascular risk.

Psychotropic drugs, like antipsychotics and antidepressants, are often associated with metabolic side effects such as weight gain and an increased risk of the development of diabetes and an atherogenic lipid profile. These adverse effects not only bear a high cardiovascular risk and lead to higher morbidity and mortality, but are an additional burden to mentally ill patients and can be a decisive factor for the compliance and, consequently, the success of the therapy. Second generation antipsychotics (SGAs), in particular, clozapine and olanzapine, lead to significant weight gain and impair glucose metabolism. Despite the availability of newer SGAs, such as aripiprazole, which are considered to be less prone to cause metabolic side effects, olanzapine is still one of the most prescribed SGAs worldwide. Antidepressant drugs may also induce weight again and diabetes even though the literature is contradictory, probably due to different receptor affinities. This review aims to provide an overview of the metabolic side effects caused by commonly used psychotropic drugs and give insight into underlying mechanisms.

Objective: Pronounced weight loss after bariatric surgery was demonstrated to have significant beneficial effects on surrogates of early atherosclerosis. The aim of this prospective examination was to investigate whether these improvements of endothelial function and vascular structure are persistent in the long-term. Design and Methods: A total of 52 obese adults were examined before and 5 years after bariatric surgery. Carotid intima media thickness (IMT), brachial flow-mediated dilation (FMD), abdominal fat distribution, and metabolic parameters were determined. Additional 18 months data were available from 27 patients. Results: After 5 years, mean weight loss ± SD of 25% ± 12 in all subjects was accompanied by known improvements in metabolism. Change in IMT was −0.02 mm ± 0.007, whereas FMD improved by +1.5% ± 0.5. In the subgroup IMT decreased by 0.04 mm ± 0.06 within the first 18 months, whereas no significant change was observed between 18 month and 5 years. FMD improved by 3.8% ± 0.6 after 18 months followed by a nonsignificant decrease of −1.4% ± 0.9. Conclusions: These long-term results demonstrate that bariatric surgery-induced weight loss improves both functional and structural markers of early atherosclerosis providing further evidence for the beneficial effects of weight loss on obesity-associated alterations of the vasculature.

Objective: The accuracy of anthropometric surrogate markers such as the body adiposity index (BAI) and other common indexes like the body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) to predict metabolic sequelae is essential for its use in clinical practice. Design and Methods: Thus, we evaluated the strength of BAI and other indexes to relate with anthropometric parameters, adipocytokines, blood lipids, parameters of glucose-homeostasis and blood pressure in 1,770 patients from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study in a crosssectional design. Measurements were BAI, BMI, WHR, WHtR, abdominal subcutaneous and visceral adipose tissue (aSAT and VAT), total body adipose tissue mass, body weight, waist- and hip circumference (WC and HC), leptin, adiponectin, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), fasting plasma glucose, fasting plasma insulin, the homeostasis model assessment of insulin resistance (HOMAIR), systolic and diastolic blood pressure. Results and Conclusions: BAI was significantly associated with leptin and HC. We conclude that BAI was the best calculator for leptin. BAI was inferior to BMI to predict anthropometric parameters other than HC, adiponectin, blood lipids, parameters of glucose homeostasis, and blood pressure in this cross-sectional study.

Obesity leads to the activation of pro-inflammatory pathways, resulting in a state of low-grade inflammation. Recently, several studies have shown that the exposure to lipopolysaccharide (LPS) could initiate and maintain a chronic state of low-grade inflammation in obese people. As the daily intake of food additives has increased substantially, the aim of the present study was to investigate a potential influence of food additives on the release of leptin, IL-6 and nitrite in the presence of LPS in murine adipocytes. Leptin, IL-6 and nitrite concentrations were analysed in the supernatants of murine 3T3-L1 adipocytes after co-incubation with LPS and the food preservatives, sodium sulphite (SS), sodium benzoate (SB) and the spice and colourant, curcumin, for 24 h. In addition, the kinetics of leptin secretion was analysed. A significant and dose-dependent decrease in leptin was observed after incubating the cells with SB and curcumin for 12 and 24 h, whereas SS decreased leptin concentrations after 24 h of treatment. Moreover, SS increased, while curcumin decreased LPS-stimulated secretion of IL-6, whereas SB had no such effect. None of the compounds that were investigated influenced nitrite production. The food additives SS, SB and curcumin affect the leptin release after co-incubation with LPS from cultured adipocytes in a dose- and time-dependent manner. Decreased leptin release during the consumption of nutrition-derived food additives could decrease the amount of circulating leptin to which the central nervous system is exposed and may therefore contribute to an obesogenic environment.

Psychotropic drugs, such as antipsychotics and antidepressants, are widely used substances which can display marked metabolic side effects. Psychiatric patients display increased morbidity and mortality which, besides disease specific factors, may be attributed to metabolic side effects of psychotropic drugs. Commonly observed side effects of antipsychotics are weight gain as well as disturbances in glucose and lipid metabolism. Additionally, antipsychotics have been shown to increase diabetes risk. Also, the use of some of the antidepressant substances is associated with an increased diabetes risk. However, large inter-substance variations have been observed. Conversely, diabetics have an increased risk of depression. Metabolic side effects of psychotropic drugs pose a serious impairment for psychiatric patients and their management can play a pivotal role in therapeutic compliance and success. This review aims to give an overview of metabolic side effects of commonly used psychotic drugs and to give an insight into possible underlying mechanisms.

Background Apolipoprotein A5 (apoA5) is a recently described liver-specific protein that has been shown to influence triglyceride (TG) metabolism. ApoA5 transgenic mice display dramatically reduced TG levels, while in contrast apoA5 deficiency in humans was reported to result in marked hypertriglyceridemia. ApoA5 exerts its extracellular effects by increasing lipolysis of TG-rich lipoproteins, while in vitro data suggest additional intrahepatic effects. Methods In this study the authors set out to investigate a possible role of apoA5 in non-alcoholic fatty liver disease (NAFLD). We thus determined hepatic apoA5 expression in 15 obese subjects with histologically proven NAFLD undergoing bariatric surgery. In addition, the authors established a hepatic cell culture model of apoA5 knockdown by transfecting human hepatoma cells (HepG2) with apoA5 small interfering (si) RNA, and determined intracellular TG content and expression levels of key enzymes and transcription factors of intrahepatic lipid metabolism in these cells. Results Pronounced weight loss and associated histologically verified improvement of hepatic steatosis were accompanied by significant reductions of hepatic apoA5 mRNA expression levels. Significant apoA5 knockdown in HepG2 cells resulted in a marked decrease of intracellular TG content. When HepG2 cells were co-transfected with apoA5 and peroxisome proliferator-activated receptor gamma (PPARγ), reductions in hepatic TG accumulation were significantly less pronounced when compared to apoA5 siRNA transfected HepG2 cells. Conclusions In obese subjects, hepatic apoA5 mRNA expression decreases after weight loss and improvements in hepatic steatosis. The authors9 in vitro data demonstrate that apoA5 influences intrahepatic TG metabolism and that these intracellular effects of apoA5 are accompanied by changes in PPARγ mRNA expression. In summary, the data suggest that as well as several other factors, apoA5 might be involved in the pathogenesis of hepatic steatosis.

Eur J Clin Invest 2011; 41 (9): 937–942 Abstract Background Cumulating evidence suggests that the broadly acting neurotrophic pigment epithelium-derived factor is associated with visceral adiposity, the metabolic syndrome, diabetes and exerts beneficial effects on atherosclerosis. To further elucidate the relationship between pigment epithelium-derived factor and metabolic perturbations characteristic of obesity, we examined the effect of pronounced weight loss on serum levels of pigment epithelium-derived factor. Materials and methods Thirty-six severely obese adults were examined before and 18 months after bariatric surgery. Abdominal fat distribution was determined by ultrasound, metabolic parameters by standard methods, pro-inflammatory biomarkers and serum pigment epithelium-derived factor levels by enzyme-linked immunosorbent assay. Results Bariatric surgery resulted in a mean body mass index (BMI) reduction of 9·0 ± 5·0 kg m−2 and concomitant improvements in glucose homoeostasis and lipid profile. Pigment epithelium-derived factor serum levels decreased from a median 11·0 μg mL−1 (interquartile range: 3·8) to 9·2 μg mL−1 (interquartile range: 4·5) (P 0·370, P

Objective Patients with schizophrenia often experience sexual dysfunction (SD), to which disorder-related factors like negative symptoms and nondisorder-related factors can theoretically contribute. Thus, we investigated the correlation of SD and serum prolactin level in patients with schizophrenia during antipsychotic treatment. Methods We included 39 patients with schizophrenia with a mean age of 34.6 years who were switched to second-generation antipsychotics into the study. Sexual adverse effects (via a specific scale) and serum prolactin levels were measured at baseline and week 4. Results In males, mean prolactin levels increased over 4 weeks at a trend level of significance. Although a high incidence of SD was reported at baseline, there were no statistically significant changes over the course of 4 weeks. At baseline, a positive correlation between diminished sexual desire and prolactin levels could be found in men, which was not found in women; at week 4, both male and female patients demonstrated a positive correlation between orgastic dysfunction and prolactin levels. We found significant positive correlations between changes in prolactin levels over 4 weeks and changes in orgastic dysfunction for both sexes. Regression analyses showed prolactin levels at baseline to be a predictor of diminished sexual desire in men. Change in prolactin level was found to be a predictor of change for diminished sexual desire in women and for orgastic dysfunction in both sexes. Conclusion We conclude that the potential of antipsychotics to increase serum prolactin levels imposes a certain risk that patients will experience SD of varying severity.

The prevalence of obesity is rising worldwide. Recent research findings show that adipose tissue is a highly active endocrine organ, which is involved in many physiological processes. These metabolic processes are influenced by products of the adipose tissue, so-called adipokines, which play a crucial role in the pathogenesis of the metabolic syndrome and cardiovascular disease. In addition, the two major fat depots - intraabdominal and subcutaneous - differ in their ability to secrete adipokines. In recent years the importance of the association between intraabdominal fat and the development of insulin resistance, diabetes mellitus type 2 and dyslipidemia was recognized. Therefore, accumulation of visceral adipose tissue contributes due to its ability to secrete a different pattern of adipokines to increased morbidity and mortality. This review aims to characterize novel, newly recognized adipokines and to discuss their roles in the pathogenesis of insulin resistance and atherosclerosis, as well as other metabolic complications.

Background. Matrix metalloproteinases (MMPs) and their specific inhibitors (tissue inhibitor of metalloproteinases [TIMPs]), are involved in adipogenesis, angiogenesis and remodeling of extracellular matrix. MMPs and TIMPs have been shown to be associated with various diseases such as neurological disorders, malignancies and cardiovascular disease. MMPs and TIMPs are thought to play a major role in extensive reorganization of the adipose tissue in obesity. Methods and materials. To test whether significant weight loss alters circulating MMPs and TIMPs, 18 morbidly obese women, who underwent bariatric surgery for weight loss, were investigated before and one year after surgery in a prospective design study. Body composition, glucose and lipid metabolism parameters were determined in all study subjects before and after weight loss. Circulating MMP-2, -3, -7 and TIMP-1, -2 and -4 serum levels were measured using commercially available, enzyme-linked immunoassays. Results. Pronounced weight loss was accompanied by improvements in glucose homeostasis and lipid parameters. In the mean time MMP-2 and MMP-3, as well as TIMP-1, -2 and TIMP-4 concentrations were not affected by significant weight loss, and circulating MMP-7 increased significantly after bariatric surgery, although without reaching the standard levels as determined in 18, lean, healthy women. Conclusion. Our data indicate that reduced MMP-7 levels in obesity might be restored by significant weight loss, suggesting that the reorganization of adipose tissue in obesity might be partially reversible by weight reduction. We hypothesize that increased circulating MMP-7 might indicate enhanced adipocyte differentiation in subjects who had undergone bariatric surgery.

Adipocyte fatty acid binding protein (A-FABP) has been suggested to play an important role in fat metabolism linking obesity and the metabolic syndrome. Increasing A-FABP plasma levels were observed during greatest weight loss after bariatric surgery suggesting that A-FABP may indicate changes in fat mass in dynamic situations. As there are no data on weight gain, we investigated the effect of refeeding anorexic patients on body composition and A-FABP plasma levels. Parameters of glucose and lipid metabolism as well as plasma levels of leptin and A-FABP were prospectively assessed in 16 female patients with anorexia nervosa during inpatient weight restoration. Body composition was determined by multifrequency body impedance analysis. After 28 days, fat mass increased from 4.4 ± 2.5 kg at baseline to 5.5 ± 2.2 kg (P

SummaryValproic acid (VPA) is an effective and widely used anticonvulsant, associated with metabolic adverse effects such as weight gain, hyperinsulinemia, hyperleptinemia and hypoadiponectinemia. The aim of this study was to evaluate the influence of VPA and topiramate (TPM) on adiponectin binding receptors, adipoR1 and adipoR2, in human liver cancer cells, HepG2. AdipoR1 but not adipoR2 gene expression was upregulated by VPA treatment. TPM did neither affect adipoR1 nor adipoR2 gene expression. Given the tight association between VPA treatment, metabolic side effects and the adipocytokine-axis, upregulation of adipoR1 possibly represents a favoured and insulin-sensitizing mechanism.

Background Adiponectin is an insulin-sensitizing, antiatherogenic and anti-inflammatory adipocytokine that circulates in three isoforms: a trimer [low-molecular weight (LMW)], a hexamer (trimer-dimer) of medium molecular weight (MMW) and a multimeric high molecular weight (HMW) isoform. Evidence is accumulating that HMW adiponectin is the active isoform of the adipocytokine. We investigated the impact of adipose tissue and insulin sensitivity on adiponectin isoform distribution. Materials and methods One hundred and eighty-seven normolipidaemic, non-diabetic lean or obese subjects with or without insulin resistance participating in the Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk (SAPHIR) were included in the study. Insulin sensitivity was determined by the short insulin tolerance test and the homeostasis model assessment (HOMA) index. Serum adiponectin isoform distribution was determined by an enzyme immunoassay. Results Total adiponectin as well as HMW/total adiponectin ratio was significantly increased in female subjects. Circulating total adiponectin levels were lowest in obese patients due to reduced concentrations of HMW adiponectin. As determined by stepwise regression analysis, besides age and high density lipoprotein (HDL) cholesterol, visceral fat area and waist-to-hip ratio predicted concentrations of HMW adiponectin, while insulin sensitivity had no influence on either total adiponectin or its isoforms. Conclusions Our results underline that determination of adiponectin isoforms are more useful than measurement of total adiponectin in clinical settings. Our data suggest that adiponectin concentrations are strongly associated with visceral fat area but not with insulin sensitivity. Thus, we hypothesize that insulin resistance is a consequence rather than the cause of hypoadiponectinaemia in obese subjects.

Background Weight loss induced by bariatric surgery is an effective method to reverse obesity and comorbidities. The aim of this prospective weight loss study was to investigate changes of body fat distribution in relation to adiponectin and its isoforms and further to investigate the influence of both body fat distribution and adiponectin on the degree of liver steatosis. Design Fifteen severely obese female patients (body mass index 43·1 ± 4·1, mean age 34·5 ± 8·6 years) were examined before and after surgical treatment. Grading of fatty liver disease and the subcutaneous and visceral fat diameters were determined by abdominal ultrasonography. Metabolic parameters were determined using standard methods; serum total adiponectin and its isoforms were detected by enzyme immuno assay (EIA). Results Mean weight loss was 28·3 kg, which was mostly due to a loss in fat mass, accompanied by an increase in total adiponectin and the high molecular weight (HMW) adiponectin isoform. Visceral adipose tissue (VAT) diameter was highly correlated with liver steatosis, even more strongly than the parameters of liver function. In addition, liver steatosis correlated negatively with HMW adiponectin and binary logistic regression revealed that changes in fat mass, HMW adiponectin and alanine aminotransferase (ALT) were the best predictors for changes in the degree of hepatic steatosis. Conclusions Our results suggest that circulating HMW adiponectin is associated with both VAT and liver steatosis. In summary, the major findings were that the VAT diameter is highly correlated with liver steatosis, even stronger than the parameters of liver function and the association of HMW adiponectin with liver steatosis was better than with total adiponectin.

The use of second-generation antipsychotics (SGAs) is associated with metabolic side effects including weight gain, diabetes mellitus and an atherogenic lipid profile. These adverse effects are not only the risk factors for cardiovascular disease, insulin resistance and diabetes mellitus leading to increased morbidity and mortality but may also impair the patient's adherence to treatment. SGAs in particular are associated with significant weight gain with clozapine and olanzapine carrying the highest risk, whereas newer agents, such as risperidone and aripiprazole, are considered to be less prone to cause weight gain. Consequently, a consensus development conference convened issuing recommendations on patient monitoring when treated with SGAs. The metabolic effects of antipsychotic drugs should be of concern when planning a patient's treatment strategy. Baseline screening and regular follow-up monitoring whose intervals should depend on the individual predisposition are advised. Possible therapeutical strategies for the management of drug-induced obesity include therapeutic approaches, such as life style change and pharmaceutical intervention. Drugs with a weight reducing effect become more important because of the lack of compliance with behavioural intervention. Topiramate, histamine-antagonists, dopaminergic- and serotoninergic agents have shown positive results in the management of psychotropic medication induced weight gain. However, further trials are required to support a specific therapeutical approach as well as studies to investigate the underlying mechanisms for future drug development.

Obesity contributes to telomere attrition. Studies focusing on short-term effects of weight loss have been unable to identify protection of telomere length. This study investigates long-term effects of pronounced weight loss induced by bariatric surgery on telomere length.One hundred forty-two patients were recruited in a prospective, controlled intervention study, follow-up investigations were done after 10.46±1.48 years. A control group of normal weight participants was recruited and followed from 1995 to 2005 in the Bruneck Study. A total of 110 participants from each study was matched by age and sex to compare changes in telomere length. Quantitative PCR was used to determine telomere length.Telomere length increased significantly by 0.024±0.14 (P=0.047) in 142 bariatric patients within 10 years after surgery. The increase was different from telomere attrition in an age- and sex-matched cohort population of the Bruneck Study (-0.057±0.18; β=0.08; P=0.003). Significant changes in telomere length disappeared after adjusting for baseline body mass index (BMI) because of general differences in BMI and telomere length between the two study populations (β=0.07; P=0.06). Age was proportional to telomere length in matched bariatric patients (r=0.188; P=0.049) but inversely correlated with telomere length in participants of the Bruneck Study (r=-0.197; P=0.039). There was no association between percent BMI/excess weight loss and telomere attrition in bariatric patients. Baseline telomere length in bariatric patients was inversely associated with baseline plasma cholesterol and triglyceride concentrations. Telomere shortening was associated with lower high-density lipoprotein cholesterol and higher fasting glucose concentration at baseline in bariatric patients.Increases in relative telomere length were found after bariatric surgery in the long term, presumably due to amelioration of metabolic traits. This may overrule the influence of age and baseline telomere length and facilitate telomere protection in patients experiencing pronounced weight loss.

Valproic acid (VPA), as one of the most widely prescribed antiepileptic drugs (AED) for many types of epilepsy in adults and children, is associated with weight gain, alteration of adipocytokine homeostasis, insulin resistance and Non-Alcoholic Fatty Liver Disease (NAFLD). Retinol-binding protein 4 (RBP4) and Glucagon-like peptide-1 (GLP-1) are considered as important new targets in modern type 2 diabetes mellitus therapy linked to insulin resistance, NAFLD and visceral obesity acting via peripheral or central mechanisms. We herein demonstrate the lack of an influence of VPA treatment on RBP4 and GLP-1 in otherwise healthy patients. In summary, the absence of any relationship with RBP4 and GLP-1 concentrations does not suggest a role of these novel insulin resistance parameters as potential regulators of glucose and fat metabolism during VPA-therapy.

The accuracy of anthropometric surrogate markers such as the body adiposity index (BAI) and other common indexes like the body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) to predict metabolic sequelae is essential for its use in clinical practice.Thus, we evaluated the strength of BAI and other indexes to relate with anthropometric parameters, adipocytokines, blood lipids, parameters of glucose-homeostasis and blood pressure in 1,770 patients from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study in a crosssectional design. Measurements were BAI, BMI, WHR, WHtR, abdominal subcutaneous and visceral adipose tissue (aSAT and VAT), total body adipose tissue mass, body weight, waist- and hip circumference (WC and HC), leptin, adiponectin, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), fasting plasma glucose, fasting plasma insulin, the homeostasis model assessment of insulin resistance (HOMAIR), systolic and diastolic blood pressure.BAI was significantly associated with leptin and HC. We conclude that BAI was the best calculator for leptin. BAI was inferior to BMI to predict anthropometric parameters other than HC, adiponectin, blood lipids, parameters of glucose homeostasis, and blood pressure in this cross-sectional study.

Psychotropic drugs, such as antipsychotics and antidepressants, are widely used substances which can display marked metabolic side effects. Psychiatric patients display increased morbidity and mortality which, besides disease specific factors, may be attributed to metabolic side effects of psychotropic drugs. Commonly observed side effects of antipsychotics are weight gain as well as disturbances in glucose and lipid metabolism. Additionally, antipsychotics have been shown to increase diabetes risk. Also, the use of some of the antidepressant substances is associated with an increased diabetes risk. However, large inter-substance variations have been observed. Conversely, diabetics have an increased risk of depression. Metabolic side effects of psychotropic drugs pose a serious impairment for psychiatric patients and their management can play a pivotal role in therapeutic compliance and success. This review aims to give an overview of metabolic side effects of commonly used psychotic drugs and to give an insight into possible underlying mechanisms.

Cumulating evidence suggests that the broadly acting neurotrophic pigment epithelium-derived factor is associated with visceral adiposity, the metabolic syndrome, diabetes and exerts beneficial effects on atherosclerosis. To further elucidate the relationship between pigment epithelium-derived factor and metabolic perturbations characteristic of obesity, we examined the effect of pronounced weight loss on serum levels of pigment epithelium-derived factor.Thirty-six severely obese adults were examined before and 18 months after bariatric surgery. Abdominal fat distribution was determined by ultrasound, metabolic parameters by standard methods, pro-inflammatory biomarkers and serum pigment epithelium-derived factor levels by enzyme-linked immunosorbent assay.Bariatric surgery resulted in a mean body mass index (BMI) reduction of 9·0 ± 5·0 kg m(-2) and concomitant improvements in glucose homoeostasis and lipid profile. Pigment epithelium-derived factor serum levels decreased from a median 11·0 μg mL(-1) (interquartile range: 3·8) to 9·2 μg mL(-1) (interquartile range: 4·5) (P0·0001). In univariate analysis, relative change in pigment epithelium-derived factor levels was significantly associated with change in weight, BMI, fat mass, visceral fat diameter, insulin, homoeostasis model for insulin resistance, triglyceride and leptin levels (all r0·370, P0·05). No associations were observed for C-reactive protein, interleukin-6 or tumour necrosis factor alpha. After adjustment for age, sex and smoking status, associations remained significant.The beneficial effects of bariatric surgery-induced pronounced weight loss on glucose homoeostasis may partially be attributable to visceral adipose tissue reduction and concomitantly decreasing pigment epithelium-derived factor concentrations.

Background and aims Elevated plasminogen activator inhibitor 1 (PAI-1) concentrations are a hallmark of obesity and are considered to contribute to the development of cardiovascular disease. As adipose tissue constitutes a major source for PAI-1 in obesity, we investigated the individual contribution of subcutaneous and intra-abdominal fat on PAI-1 concentrations during pronounced weight loss after bariatric surgery. Methods and results Thirty-seven obese adults were examined before and 18 months after surgery. Abdominal fat distribution was determined by ultrasound, metabolic parameters and plasma PAI-1 levels by standard methods. BMI was reduced by 9.2±4.9kg/m 2 , while total fat mass and visceral fat diameter (VFD) decreased by 20.7±11.9kg and 4.2±2.3cm, respectively. Concomitantly, PAI-1 levels diminished by 3.2±5.6ng/ml (all p ≤0.015). Change in PAI-1 levels was correlated with change in VFD ( r =0.441, p =0.008), but not with subcutaneous fat diameter. In stepwise multiple regression analysis change in VFD was an independent predictor of change in PAI-1 concentrations. When adjusted for age and sex or total fat mass associations between PAI-1 and VFD remained significant. Conclusion We demonstrate that VFD is a major determinant for PAI-1 concentrations during pronounced weight loss after bariatric surgery. Thus, significant reduction of visceral fat mass may contribute to the reduced cardiovascular morbidity and mortality after bariatric surgery by a concomitant decrease in PAI-1 concentrations.

Eur J Clin Invest 2010; 40 (3): 277–280 Abstract Background Subclinical inflammation in obesity is critical for development of several obesity-associated disorders. We set out to investigate the effect of pronounced weight loss on circulating chemerin levels, a chemoattractant protein that also influences adipose cell function by paracrine and autocrine mechanisms. Material and methods Thirty-two obese patients undergoing bariatric surgery were tested before and on an average of 18 months after gastric banding or gastric bypass surgery. Results Pronounced weight loss after bariatric surgery was accompanied by improvements in parameters of lipid and glucose metabolism and increased adiponectin levels. Chemoattractant chemerin significantly decreased from 175·91 ± 24·50 to 145·53 ± 26·44 ng mL−1 after bariatric surgery (P ≤ 0·01). Concomitantly, hs-CRP as a marker of subclinical inflammation was significantly reduced after weight reduction (P ≤ 0·01). Conclusions We hypothesize that weight-loss induced reduction in circulating chemerin might in conjunction with other factors be associated with diminished recruitment of macrophages in adipose tissue and reduction of subclinical inflammation, which again could partly explain beneficial long-term effects of weight reduction in obese subjects.

Initial optimism regarding the introduction of second-generation antipsychotic drugs has decreased because of accumulating concerns regarding efficacy and safety issues, particularly in terms of weight gain and disturbances in glucose and lipid metabolism. These adverse effects, in addition to posing serious health risks, significantly compromise patient compliance and contribute to overall lack of therapy effectiveness. Consequently, research efforts have been directed toward the development of new pharmacological treatment options for schizophrenia and bipolar disorder that are both efficacious and well tolerated. This review discusses some of the most recently developed antipsychotic compounds that have undergone clinical assessment from the perspective of their metabolic impact.

The prevalence of obesity is rising worldwide. Recent research findings show that adipose tissue is a highly active endocrine organ, which is involved in many physiological processes. These metabolic processes are influenced by products of the adipose tissue, so-called adipokines, which play a crucial role in the pathogenesis of the metabolic syndrome and cardiovascular disease. In addition, the two major fat depots - intraabdominal and subcutaneous - differ in their ability to secrete adipokines. In recent years the importance of the association between intraabdominal fat and the development of insulin resistance, diabetes mellitus type 2 and dyslipidemia was recognized. Therefore, accumulation of visceral adipose tissue contributes due to its ability to secrete a different pattern of adipokines to increased morbidity and mortality. This review aims to characterize novel, newly recognized adipokines and to discuss their roles in the pathogenesis of insulin resistance and atherosclerosis, as well as other metabolic complications.

Aims To bridge the beneficial metabolic effects of pronounced weight loss on one side and the data on morbidity and mortality on the other side, we investigated the impact of profound weight loss on structural and functional markers of early atherosclerosis. Methods and results Thirty-seven obese adults were examined before and 18 months after bariatric surgery. Carotid intima–media thickness (CIMT), brachial flow-mediated dilation (FMD), nitroglycerine-mediated dilation, and abdominal fat distribution were assessed by high-resolution ultrasound. Surgery resulted in a body mass index decrease of 9.1 ± 4.9 kg/m2 with concomitant improvements in glucose and lipid metabolism. Carotid intima–media thickness diminished from 0.56 ± 0.09 to 0.53 ± 0.08 mm ( n = 37; P = 0.004). Flow-mediated dilation improved from 5.81 ± 3.25 to 9.01 ± 2.93% ( n = 25; P < 0.001). Both CIMT and FMD were associated with intra-abdominal fat diameter. Conclusion The present results demonstrate that bariatric surgery-induced diminution of visceral fat improves both functional and structural markers of early atherosclerosis, providing a link between the weight loss-associated improvements of traditional and non-traditional risk factors and the reduced long-term morbidity and mortality after bariatric surgery.

Background and aims Several studies indicate that changes in the plasma concentrations of adipocyte-fatty acid binding protein (A-FABP), retinol binding protein-4 (RBP-4) and visfatin are associated with chronic states of insulin resistance. Recent studies have shown that postprandial lipemia induces an acute state of insulin resistance. The aim of this study was to investigate the effect of postprandial lipemia on the plasma concentrations of A-FABP, RBP-4 and visfatin. Methods and results In a within-subject crossover study, we administered a standardized high-fat meal to 24 healthy subjects (12 males and 12 females). Plasma concentrations of adipocytokines were measured in the morning after an overnight fast and during postprandial lipemia, i.e. 2, 4 and 6 hours after meal ingestion (postprandial experiment). To exclude potential confounding factors affecting the adipocytokine plasma concentrations, a control experiment without meal ingestion was performed over the same time period (postabsorptive control experiment). Comparing plasma concentrations of A-FABP, RBP-4 and visfatin between the postprandial and the postabsorptive control experiments, we found no significant differences. Within either of the two experiments, a decrease of A-FABP was noted reaching, however, statistical significance only in the postprandial experiment, i.e. 2 and 4 hours after meal ingestion. Conclusion Postprandial lipemia has no significant effect on the plasma concentrations of visfatin, A-FABP or RBP-4 in relation to their postabsorptive plasma profiles. We conclude that prolonged states of insulin resistance are required to affect plasma concentrations of these adipocytokines.

Background: Due to the association of second generation antipsychotics (SGAs) with weight gain and alterations of glucose and lipid homeostasis, we aimed to group six commonly prescribed SGAs into classes of differing risks. Methods: Twenty-eight patients meeting the criteria for a diagnosis of schizophrenic disorder according to ICD-10 were assigned to mono-therapy with olanzapine, clozapine, quetiapine, amisulpride, ziprasidone or risperidone. The levels of glucose and lipid metabolism were assessed before and after 28 days of treatment. Results: Based on cluster analysis, olanzapine and clozapine were found to constitute a high-risk group for metabolic dysregulation while amisulpride, quetiapine, risperidone and ziprasidone could be assigned to a non-high-risk group. Subjects from the high-risk group displayed significant weight gain with concomitant increases of HOMA-IR, levels of insulin, total cholesterol, TG, LDL-C and leptin. No significant changes were observed in the non-high-risk group. Conclusion: The results of this study support the conclusion of the Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes that certain SGAs are associated with a higher risk for weight gain, insulin resistance and dyslipidemia.

Retinol-binding protein 4 (RBP-4) has been reported to be associated with visceral-fat accumulation and parameters of the metabolic syndrome (MetS). In this study, we investigated the relationship between RBP-4, visceral fat, and the MetS during pronounced weight loss after bariatric surgery. Thirty-six subjects were examined before and 2 years after surgery. Abdominal-fat distribution was determined by ultrasound, metabolic parameters, and serum RBP-4 levels by standard methods. After surgery BMI decreased by 9.07 kg/m(2), visceral-fat diameter (VFD) decreased by 60.6%, and RBP-4 serum levels by 16.6%. Change of RBP-4 levels was associated with reductions of waist (r = 0.364, P = 0.037), waist-to-hip ratio (WHR) (r = 0.415, P = 0.016), and VFD (r = 0.425, P = 0.010). MetS, as defined by International Diabetes Federation (IDF), was present in 19 patients at baseline and in nine patients at follow-up. Change in RBP-4 levels was the best predictor for the diagnosis of MetS at follow-up. In the subgroup without MetS at baseline, the decrease in RBP-4 levels (-28.1% vs. -6.3%, P = 0.020) and reduction in VFD (-66.9% vs. -55.0%, P = 0.038) were significantly greater compared to the subgroup with MetS. We demonstrate a marked decrease of RBP-4 levels after bariatric surgery, which correlates with reduction in visceral-fat mass. Furthermore, the extent of changes in RBP-4 levels differs according to the severity of the MetS.

Antipsychotika der neuen Generation verdrangen vermehrt die klassischen Antipsychotika, vor allem wegen des geringeren Risikos Nebenwirkungen des extrapyramidalmotorischen Systems hervorzurufen und aufgrund einiger therapeutischer Vorteile. Die Verwendung der Antipsychotika der neuen Generation wird jedoch vermehrt mit starker Gewichtszunahme, der Induktion einer Insulinresistenz und eines atherogenen Lipidprofils assoziiert. Unter diesen Substanzen fuhren Clozapin und Olanzapin zur starksten Gewichtszunahme, hauptsachlich uber eine Vermehrung des Korperfettes, und zu Veranderungen der Glukosehomoostase. In den meisten Fallen trat ein Diabetes mellitus bereits innerhalb von Tagen bis Wochen nach Therapiebeginn mit diesen Antipsychotika auf, in den meisten Fallen waren die neu aufgetretenen Storungen der Glukosehomoostase nach Absetzen der Medikation reversibel und einige Berichte beschreiben ein erneutes Auftreten bei neuerlicher Behandlung mit derselben Medikation. Ein moglicher Pathomechanismus fur die Entstehung einer Hyperglykamie unter Therapie mit Antipsychotika der neuen Generation stellt die Beeintrachtigung der Insulinwirkung uber humorale und/oder zellulare Mechanismen dar. Alternativ konnte ein durch Antipsychotika induzierter Diabetes mellitus sekundar durch eine Gewichtszunahme entstehen oder infolge einer Veranderung der Fettverteilung, insbesondere einer Vermehrung der viszeralen Fettdepots, oder durch eine direkte Wirkung an insulinsensitiven Geweben. In diesem Artikel geben wir einen Uberblick uber die metabolischen Nebenwirkungen unter der Therapie mit Antipsychotika der neuen Generation, versuchen den Pathomechanismus dieser Nebenwirkungen zu beleuchten und mochten mogliche zukunftige Therapieansatze darstellen und diskutieren.

Obesity is associated with lipid abnormalities leading to an increased morbidity and mortality from atherosclerotic disease. Lipid transfer proteins such as Cholesteryl Ester Transfer Protein (CETP) and Phospholipid Transfer Protein (PLTP), and lipases such as lipoprotein lipase (LPL) and hepatic lipase (HL) are involved in the pathogenesis of the obesity associated proatherogenic dyslipidemia. Nineteen severely obese female subjects undergoing laparosopic gastric banding participated in this prospective study. Subjects were examined with respect to body composition, lipid profile, CETP, PLTP, LPL and HL before and 1 year after surgical treatment. Mean weight loss was 22.2 kg, mainly due to losses in the fat depots. Triglycerides decreased and HDL(2)-C increased significantly. In respect to transfer proteins mean CETP mass decreased from 1.82 to 1.71 microg mL(-1) (P = 0.043) and mean PLTP activity was reduced from 7.15 to 6.12 micromol mL(-1) h(-1) (P = 0.002), in parallel. In addition, both mean LPL activity and mean HL activity tended to decrease from 297 to 248 nmol mL(-1) h(-1) for LPL (P = 0.139) and from 371 to 319 nmol mL(-1) h(-1) for HL (P = 0.170), respectively. We conclude that weight loss induced by bariatric surgery is associated with the amelioration of the obesity-associated dyslipidemic state. This improvement may be attributable to decreased mass and action of the adipocyte tissue derived lipid transfer proteins CETP and PLTP.

Background Serotonin (5-HT) improves insulin sensitivity and glucose metabolism, however, the underlying molecular mechanism has remained elusive. Previous studies suggest that 5-HT can activate intracellular small GTPases directly by covalent binding, a process termed serotonylation. Activated small GTPases have been associated with increased GLUT4 translocation to the cell membrane. Therefore, we investigated whether serotonylation of small GTPases may be involved in improving Insulin sensitivity and glucose metabolism. Methods Using fully differentiated L6 rat skeletal muscle cells, we studied the effect of 5-HT in the absence or presence of insulin on glycogen synthesis, glucose uptake and GLUT4 translocation. To prove our L6 model we additionally performed preliminary experiments in C2C12 murine skeletal muscle cells. Results Incubation with 5-HT led to an increase in deoxyglucose uptake in a concentration-dependent fashion. Accordingly, GLUT4 translocation to the cell membrane and glycogen content were increased. These effects of 5-HT on Glucose metabolism could be augmented by co-incubation with insulin and blunted by co incubation of 5-HT with monodansylcadaverine, an inhibitor of protein serotonylation. In accordance with this observation, incubation with 5-HT resulted in serotonylation of a protein with a molecular weight of approximately 25 kDa. We identified this protein as the small GTPase Rab4, the activity of which has been shown to be stimulated by both insulin signalling and serotonylation. Conclusion Our data suggest that 5-HT elicits its beneficial effects on Glucose metabolism through serotonylation of Rab4, which likely represents the converging point between the insulin and the 5-HT signalling cascades.