Long-term effects of weight loss after bariatric surgery on functional and structural markers of atherosclerosis.

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.

The novel insulin resistance parameters RBP4 and GLP-1 in patients treated with valproic acid: just a sidestep?

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.

Plasminogen activator inhibitor 1 and visceral obesity during pronounced weight loss after bariatric surgery.

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 ± 4.9 kg/m(2), while total fat mass and visceral fat diameter (VFD) decreased by 20.7 ± 11.9 kg and 4.2 ± 2.3 cm, respectively. Concomitantly, PAI-1 levels diminished by 3.2 ± 5.6 ng/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.

The role of apolipoprotein A5 in non-alcoholic fatty liver disease.

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 authors' 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.

Pharmacological and non-pharmacological treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) comprises a disease spectrum ranging from simple steatosis and steatohepatitis to cirrhosis. Based on its strongest risk factors namely visceral obesity and insulin resistance, NAFLD is thought to be the hepatic manifestation of the metabolic syndrome and is considered to be the most common liver disorder in Western countries. Pathophysiological mechanisms include an enlarged pool of fatty acids, subclinical inflammation, oxidative stress and imbalances of various adipocytokines such as adiponectin. Accordingly, targets for therapeutic interventions are miscellaneous: amelioration of obesity by pharmacological, surgical or lifestyle intervention has been evaluated with success in numerous, but not all studies. Some efficacy was reported for metformin and short-term glitazone treatment. In a large recently reported trial, vitamin E supplementation improved biochemical and histological markers in subjects with non-alcoholic steatohepatitis. Blockade of the endocannabinoid system has been proposed to be a promising target in NAFLD; however, very recently the cannabinoid receptor blocker rimonabant has been withdrawn because of central nervous system toxicity. Cytoprotective therapies and statins have been mainly ineffective in NAFLD. New but so far insufficiently studied therapeutic approaches include inhibitors of the renin-angiotensin system as well as incretin mimetics respectively.

Effect of bariatric surgery on circulating chemerin levels.

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 < or = 0.01). Concomitantly, hs-CRP as a marker of subclinical inflammation was significantly reduced after weight reduction (P < or = 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.

Effect of postprandial lipemia on plasma concentrations of A-FABP, RBP-4 and visfatin.

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.

Non-alcoholic fatty liver disease (NAFLD), insulin resistance and lipid profile in antiepileptic drug treatment.

PURPOSE: Patients undergoing long-term treatment with valproic acid (VPA) are prone to develop different features of the metabolic syndrome (MS). The aim of the present study was to evaluate the occurrence of non-alcoholic fatty liver disease (NAFLD), insulin resistance (IR) and a pro-atherogenic lipid profile in patients undergoing VPA, carbamazepine (CBZ) and lamotrigine (LTG) monotherapy compared to healthy controls. METHODS: Abdominal ultrasound as well as measurement of serum fasting insulin and glucose, serum lipids and liver function parameters were performed in VPA (n=23), CBZ (n=22) and LTG (n=23) treated non-diabetic and non-obese epileptic patients compared to healthy controls (n=16). RESULTS: Ultrasound measurement demonstrated characteristics of fatty liver disease in 60.9% of VPA, in 22.7% of CBZ, in 8.7% of LTG treated patients and in 12.5% of the healthy controls, with highest level of steatosis seen in VPA treated patients. In addition, patients on VPA monotherapy showed a higher body-mass index (BMI) when compared to LTG treated patients and controls (p

Effects of six second generation antipsychotics on body weight and metabolism - risk assessment and results from a prospective study.

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 monotherapy 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.

Effect of obesity and insulin sensitivity on adiponectin isoform distribution.

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.

Effect of valproic acid treatment on body composition, leptin and the soluble leptin receptor in epileptic children.

PURPOSE: The aim of the study was to determine the influence of valproic acid (VPA) treatment on leptin, the soluble leptin receptor (sOB-R), the sOB-R/leptin ratio, body composition and insulin resistance in epileptic children. METHODS: A cross-sectional cohort study was conducted at the Medical University Innsbruck, Austria. Children >6 years with idiopathic epilepsy and antiepileptic drug therapy since at least six months were eligible. Leptin concentration, the sOB-R, the sOB-R/leptin ratio, body composition and glucose homeostasis were determined. RESULTS: 87 children (median [range] age 12.8 years [6.0-18.6]) were on treatment with VPA, 55 (12.3 years [6.4-18.3]) on other AEDs, comprising the non-VPA group. VPA-treated children had higher leptin concentrations, body-mass-index standard-deviation score (SDS), body fat (each p<0.001), serum insulin concentrations (p=0.014) and homeostasis model assessment (HOMA) index (p=0.009), as well as a lower sOB-R/leptin ratio (p<0.001) when compared to the non-VPA group. Overweight VPA-treated children showed lower sOB-R concentrations and a lower sOB-R/leptin ratio (each p<0.001) as well as higher body fat and leptin levels (each p<0.001) compared to lean VPA-treated children. CONCLUSION: VPA monotherapy was associated with higher body weight, body fat and serum leptin concentrations as well as impaired glucose homeostasis. Low sOB-R concentrations and a low sOB-R/leptin ratio in overweight VPA-treated patients might contribute to disturbances in glucose homeostasis and to the development of the metabolic syndrome in these children later in life.

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. 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.

Effect of intradialytic parenteral nutrition in patients with malnutrition-inflammation complex syndrome on body weight, inflammation, serum lipids and adipocytokines: results from a pilot study.

OBJECTIVE: Evaluation of the influence of intradialytic parenteral nutrition (IDPN) in patients suffering from Malnutrition-Inflammation Complex Syndrome (MICS) on nutritional status, inflammation, adipocytokines and serum lipids. SUBJECTS: Six patients with MICS were assigned to IDPN, whereas six patients matched for age, sex, body mass index (BMI) and co-morbidity without malnutrition served as controls. Patients were recruited from Outpatient Dialysis Unit, Medical University Innsbruck and from Dialysis Unit, Hospital Feldkirch. RESULTS: In all patients with IDPN, dry body weight increased during the interventional period whereas body weight remained stable in patients without IDPN. Tumor necrosis factor (TNF)-alpha levels were higher in patients with MICS compared with controls at all time points. Total cholesterol, LDL- and HDL-levels significantly increased during dialysis at all time points in controls but not in patients with MICS. Albumin, C-reactive protein, interleukin-6 (IL-6), soluble interleukin-2 receptor (sIL-2R) and adipocytokines did not differ between patients and controls during the study period. CONCLUSIONS: IDPN in patients with MICS increases body weight despite not influencing inflammatory status. Furthermore, IDPN does not induce a pro-atherogenic lipid composition enhancing the risk for atherosclerosis. Thus, IDPN is a safe and effective treatment of malnutrition in patients with MICS.

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 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.

Comparison of different definitions of the metabolic syndrome.

BACKGROUND: The International Diabetes Federation (IDF) published a new definition of the metabolic syndrome (MetS). For this definition we compared frequency, concordance, clinical and laboratory stigmata and carotid atherosclerosis with those of the established definitions by the National Cholesterol Education Program (NCEP) and World Health Organization (WHO). MATERIALS AND METHODS: A total of 1518 subjects (943 men, 575 women) from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR), free of clinical atherosclerosis, were included in this study. To estimate insulin sensitivity two methods, i.e. homeostasis model assessment of insulin resistance (HOMA-IR) and the short insulin tolerance test, were employed. Carotid intima media thickness (IMT) and plaque extent were quantified for all subjects using high-resolution ultrasound. RESULTS: Prevalence of the MetS was 18.7% for men and 16.2% for women for the WHO definition, 18.9% and 17.0%, respectively, for the NCEP definition, and 25.8% and 19.5%, respectively, for the IDF definition. Concordance was lower between the definitions of WHO and IDF (< 50%) than between NCEP and IDF (> 67%). Compared to subjects identified by NCEP definition, subjects identified in excess by IDF (3.1-11.7%) showed less insulin resistance and lower IMT and plaque extent indistinguishable from MetS-free subjects. CONCLUSIONS: Our data suggest that the IDF definition includes subjects as MetS sufferers above these detected by NCEP or WHO, who exhibit considerably less insulin resistance and carotid atherosclerosis blurring the distinction between health and disease.

Olanzapine impairs glycogen synthesis and insulin signaling in L6 skeletal muscle cells.

Second-generation antipsychotic agents (SGAs) are increasingly replacing first-generation antipsychotic agents due to their superior activity against the negative symptoms of schizophrenia, decreased extrapyramidal symptoms and better tolerability. However, some SGAs are associated with adverse metabolic effects as significant weight gain, lipid disorders and diabetes mellitus. The pathogenesis of SGA-induced disturbances of glucose homeostasis is unclear. In vivo studies suggest a direct influence of SGAs on peripheral insulin resistance. To this end, we analyzed whether olanzapine might alter glycogen synthesis and the insulin-signaling cascade in L6 myotubes. Glycogen content was diminished in a dose- and time-dependent manner. Within the insulin-signaling cascade IRS-1 tyrosine phosphorylation was induced several fold by insulin and was diminished by preincubation with olanzapine. IRS-1-associated PI3K activity was stimulated by insulin three-fold in L6 myotubes. Olanzapine inhibited insulin-stimulated IRS-1-associated PI3K activity in a dose-dependent manner. Protein mass of AKT, GSK-3 and GS was unaltered, whereas phosphorylation of AKT and GSK-3 was diminished, and pGS was increased. Finally, we compared olanzapine with amisulpride, an SGA clinically not associated with the induction of diabetes mellitus. Glycogen content was diminished in olanzapine-preincubated L6 cells, whereas this effect was not observed under the amisulpride conditions. We conclude that olanzapine impairs glycogen synthesis via inhibition of the classical insulin-signaling cascade and that this inhibitory effect may lead to the induction of insulin resistance in olanzapine-treated patients.

Circulating adiponectin reflects severity of liver disease but not insulin sensitivity in liver cirrhosis.

BACKGROUND: The adipocytokine adiponectin has been proposed to play important roles in the regulation of energy homeostasis, insulin sensitivity and shows anti-inflammatory properties. AIM: In this study we investigated the role of circulating adiponectin in different chronic liver diseases, its regulation by systemic anti-tumour necrosis factor (TNF)-alpha treatment and its hepatic metabolism. PATIENTS AND METHODS: Plasma adiponectin levels were determined in 87 patients with liver cirrhosis of different aetiologies, seven patients with alcoholic steatohepatitis undergoing systemic anti-TNF-alpha treatment, in 11 patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt implantation and in 21 healthy controls. RESULTS: Adiponectin levels were significantly higher in all subjects with liver cirrhosis of different aetiologies when compared with healthy controls and increased dependent on Child-Pugh classification. In subjects with alcoholic steatohepatitis, systemic anti-TNF-alpha treatment caused a significant decrease in circulating adiponectin. Adiponectin concentrations were similar in portal, hepatic and peripheral veins. No correlation between adiponectin levels and insulin resistance was found in any patient group. CONCLUSIONS: Our data suggest that circulating adiponectin is increased in liver cirrhosis independent of the aetiology of liver disease. We suggest that high adiponectin levels in chronic liver disease might reflect one of the body's anti-inflammatory mechanisms in chronic liver diseases.

Effect of pronounced weight loss on the nontraditional cardiovascular risk marker matrix metalloproteinase-9 in middle-aged morbidly obese women.

OBJECTIVE: Obesity is associated with increased morbidity and mortality from atherosclerotic disease. Nontraditional cardiovascular risk factors such as C-reactive protein (CRP) and interleukin-6 (IL-6) are elevated in obese subjects and weight loss is associated with an attenuation of these risk factors. Matrix metalloproteinase-9 (MMP-9) has been linked to plaque rupture, and is, thus, a candidate marker of future myocardial events. The aim of this study was to determine the influence of weight loss on MMP-9 plasma concentrations. METHODS AND RESULTS: CRP, IL-6 and MMP-9 were analyzed from samples of 45 morbidly obese, middle-aged women before gastric banding and 1 y postsurgical treatment in this prospective study. The body mass index (BMI) of subjects decreased from 42.5+/-4.9 to 32.3+/-5.3 kg/m(2) 1 y after gastric banding. In parallel, both MMP-9 and CRP were reduced by 23 and 41%, respectively. A positive relationship was found between BMI and MMP-9 (r=0.312, P<0.05), and between CRP and IL-6 (r=0.508, P<0.05), whereas no correlation was found between CRP and MMP-9. CONCLUSIONS: We conclude that weight loss is associated with a pronounced decrease in the nontraditional cardiovascular risk markers MMP-9 and CRP, which could indicate future beneficial effects of weight loss on the cardiovascular risk in weight loosing subjects.