Julia Engl

Metabolic side effects of antipsychotic medication.

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 patients adherence to treatment.

Effect of bariatric surgery on circulating chemerin levels

Eur J Clin Invest 2010; 40 (3): 277–280

Influence of Visceral Obesity and Liver Fat on Vascular Structure and Function in Obese Subjects

Endothelial dysfunction and increased intima–media thickness (IMT) have been found in obese patients. Both regional fat distribution and liver steatosis may influence these markers of subclinical atherosclerosis. We sought to determine the interrelationships of endothelial function, carotid IMT, visceral and subcutaneous adipose tissue accumulation, and liver steatosis in severely obese subjects. In 64 severely obese patients (BMI 42.3 ± 4.3 kg/m²), we determined (i) endothelial function as flow‐mediated dilation (FMD) of the brachial artery, (ii) carotid IMT, (iii) visceral fat diameter, and (iv) degree of liver steatosis using ultrasound. FMD was associated inversely with visceral fat diameter and degree of steatosis (r = −0.577, P < 0.0001 and r = −0.523, P < 0.0001, respectively). Carotid IMT correlated with visceral fat mass (r = 0.343, P = 0.007) but not with liver steatosis. After adjustment for conventional cardiovascular risk factors, FMD was predicted independently by the visceral fat diameter, age, and sex (r2 = 0.48, P < 0.0001), but not by the degree of liver steatosis or plasma adiponectin levels. In contrast, age and sex were the only predictors of IMT (r2 = 0.33, P < 0.001). In obese patients, visceral fat diameter is a major determinant of endothelial dysfunction, independent of traditional risk factors or the degree of liver steatosis and plasma adiponectin. Measurement of visceral fat diameter by ultrasound is a novel and simple method to identify subjects with an increased risk for atherosclerosis within an obese population.

Effect of bariatric surgery on both functional and structural measures of premature atherosclerosis

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/m(2) 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.

Retinol‐binding Protein 4, Visceral Fat, and the Metabolic Syndrome: Effects of Weight Loss

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/m2, 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.

Effects of pronounced weight loss on Adiponectin oligomer composition and metabolic parameters

Objective: Adiponectin is an adipocytokine secreted into circulation in three isoforms. The aim of the study was to investigate changes of adiponectin isoforms during profound weight loss and its relation to anthropomorphometric and metabolic parameters.

Cholesteryl Ester Transfer Protein in Metabolic Syndrome

Objective: Low high‐density lipoprotein cholesterol (HDL‐C), hypertriglyceridemia, and small dense‐low density lipoprotein (LDL) are key components of metabolic syndrome (MS). Cholesteryl ester transfer protein (CETP) mediates the transfer of triglycerides (TGs) from TG‐rich lipoproteins to HDL and LDL particles in exchange for cholesteryl esters, leading to low HDL‐C and small dense‐LDL. The aim of this study was to investigate the role of CETP in subjects with MS.

Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of non-esterified fatty acid levels

Aims/hypothesisElevated fasting and postprandial plasma levels of triglyceride-rich lipoproteins (TGRLs), i.e. VLDL/remnants and chylomicrons/remnants, are a characteristic feature of insulin resistance and are considered a consequence of this state. The aim of this study was to investigate whether intact TGRL particles are capable of inducing insulin resistance.MethodsWe studied the effect of highly purified TGRLs on glycogen synthesis, glycogen synthase activity, glucose uptake, insulin signalling and intramyocellular lipid (IMCL) content using fully differentiated L6 skeletal muscle cells.ResultsIncubation with TGRLs diminished insulin-stimulated glycogen synthesis, glycogen synthase activity, glucose uptake and insulin-stimulated phosphorylation of Akt and glycogen synthase kinase 3. Insulin-stimulated tyrosine phosphorylation of IRS-1, and IRS-1- and IRS-2-associated phosphatidylinositol 3-kinase (PI3K) activity were not impaired by TGRLs, suggesting that these steps were not involved in the lipoprotein-induced effects on glucose metabolism. The overall observed effects were time- and dose-dependent and paralleled IMCL accumulation. NEFA concentration in the incubation media did not increase in the presence of TGRLs indicating that the effects observed were solely due to intact lipoprotein particles. Moreover, co-incubation of TGRLs with orlistat, a potent active-site inhibitor of various lipases, did not alter TGRL-induced effects, whereas co-incubation with receptor-associated protein (RAP), which inhibits interaction of TGRL particles with members of the LDL receptor family, reversed the TGRL-induced effects on glycogen synthesis and insulin signalling.Conclusions/interpretationOur data suggest that the accumulation of TGRLs in the blood stream of insulin-resistant patients may not only be a consequence of insulin resistance but could also be a cause for it.

Effect of pronounced weight loss on visceral fat, liver steatosis and adiponectin isoforms

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.

A-FABP—A Biomarker Associated With the Metabolic Syndrome and/or an Indicator of Weight Change?

Objective: Adipocyte fatty acid‐binding protein (A‐FABP) is a plasma biomarker recently associated with the metabolic syndrome. The aim of these studies was to investigate changes of A‐FABP during profound weight loss induced by laparoscopic adjustable gastric banding (LAGB).