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.

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.

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.

1Retinol-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.

BackgroundSerotonin (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.MethodsUsing 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.ResultsIncubation 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.ConclusionOur 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.