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Acyl coenzyme A binding protein (ACBP), also known as diazepam binding inhibitor (DBI) is a multifunctional protein with an intracellular action (as ACBP), as well as with an extracellular role (as DBI). The plasma levels of soluble ACBP/DBI are elevated in human obesity and reduced in anorexia nervosa. Accumulating evidence indicates that genetic or antibody-mediated neutralization of ACBP/DBI has anorexigenic effects, thus inhibiting food intake and inducing lipo-catabolic reactions in mice. A number of anorexiants have been withdrawn from clinical development because of their side effects including an increase in depression and suicide. For this reason, we investigated the psychiatric impact of ACBP/DBI in mouse models and patient cohorts. Intravenously (i.v.) injected ACBP/DBI protein conserved its orexigenic function when the protein was mutated to abolish acyl coenzyme A binding, but lost its appetite-stimulatory effect in mice bearing a mutation in the γ2 subunit of the γ-aminobutyric acid (GABA) A receptor (GABA A R). ACBP/DBI neutralization by intraperitoneal (i.p.) injection of a specific mAb blunted excessive food intake in starved and leptin-deficient mice, but not in ghrelin-treated animals. Neither i.v. nor i.p. injected anti-ACBP/DBI antibody affected the behavior of mice in the dark–light box and open-field test. In contrast, ACBP/DBI increased immobility in the forced swim test, while anti-ACBP/DBI antibody counteracted this sign of depression. In patients diagnosed with therapy-resistant bipolar disorder or schizophrenia, ACBP/DBI similarly correlated with body mass index (BMI), not with the psychiatric diagnosis. Patients with high levels of ACBP/DBI were at risk of dyslipidemia and this effect was independent from BMI, as indicated by multivariate analysis. In summary, it appears that ACBP/DBI neutralization has no negative impact on mood and that human depression is not associated with alterations in ACBP/DBI concentrations.

In this study, serum levels of retinol-binding protein 4, a molecule secreted by adipocytes, correlated with the magnitude of insulin resistance in subjects with obesity, impaired glucose tolerance, or type 2 diabetes and in nonobese, nondiabetic subjects with a strong family history of type 2 diabetes. Levels of this molecule appear to be elevated in serum before the development of frank diabetes and might be used to identify insulin resistance and associated cardiovascular risk factors. Levels of retinol-binding protein 4 appear to be elevated in serum before the development of frank diabetes and might be used to identify insulin resistance and associated cardiovascular risk factors. Type 2 diabetes is caused by resistance to insulin action in multiple tissues, accompanied by failure of the pancreatic beta cells to compensate sufficiently by increased insulin secretion. 1 Measurement of insulin resistance provides an early and strong predictor of type 2 diabetes. 2 Even in the absence of hyperglycemia or diabetes, insulin resistance constitutes an important risk factor for cardiovascular disease and early death. 3 Obesity, which has reached epidemic proportions worldwide, is a major cause of insulin resistance. 4 However, insulin resistance does not develop in all obese persons, and genetic background contributes strongly to insulin resistance, even in nonobese persons. 5 In . . .

Aim: Combined effects of genetic and environmental factors underlie the clustering of cardiovascular risk factors in the metabolic syndrome (MetSy). The aim was to investigate associations between several lifestyle factors and MetSy, with a focus on the possible role of smokeless tobacco in the form of Swedish moist snuff (snus). Methods: A population-based longitudinal cohort study within the Vasterbotten Intervention Programme in Northern Sweden. All inhabitants at the ages of 30, 40, 50, and 60 are invited to participate in a health survey that includes a questionnaire on psychosocial conditions and lifestyle and measurement of biological variables. Individuals examined in 1990-94 (n=24,230) and who also returned for follow-up after 10 years were included (total of 16,492 individuals: 46.6% men and 53.4% women). Regression analyses were performed. MetSy was the outcome and analyses were adjusted for age, sex, alcohol abuse, and family history of CVD and (¿abetes. Results: Ten-year development of MetSy was associated with high-dose consumption of snus at baseline (OR 1.6 [95% CI 1.26-2.15]), low education (2.2 [1.92-2.63]), physical inactivity (1.5 [1.22-1.73]) and former smoking (1.2 [1.06-1.38]). Snus was associated with separate components of MetSy, including triglycerides (1.6, 1.30-1.95), obesity (1.7 [1.36-2.18]) but not hypertension, dysglycemia and low HDL cholesterol. Conclusions: MetSy is independently associated with high consumption of snus, even when controlling for smoking status. The finding is of public health interest in societies with widespread use of snus. More research is needed to better understand the mechanisms underlying this effect.

Hyperuricemia is a common metabolic syndrome. Elevated uric acid levels are risk factors for gout, hypertension, and chronic kidney diseases. Furthermore, various epidemiological studies have also demonstrated an association between cardiovascular risks and hyperuricemia. In hyperuricemia, reactive oxygen species (ROS) are produced simultaneously with the formation of uric acid by xanthine oxidases. Intracellular uric acid has also been reported to promote the production of ROS. The ROS and the intracellular uric acid itself regulate several intracellular signaling pathways, and alterations in these pathways may result in the development of atherosclerotic lesions. In this review, we describe the effect of uric acid on various molecular signals and the potential mechanisms of atherosclerosis development in hyperuricemia. Furthermore, we discuss the efficacy of treatments for hyperuricemia to protect against the development of atherosclerosis.

Despite the success of LDL-lowering drugs in reducing cardiovascular disease (CVD), there remains a large burden of residual disease due in part to persistent dyslipidemia characterized by elevated levels of triglyceride-rich lipoproteins (TRLs) and reduced levels of HDL. This form of dyslipidemia is increasing globally as a result of the rising prevalence of obesity and metabolic syndrome. Accumulating evidence suggests that impaired hepatic clearance of cholesterol-rich TRL remnants leads to their accumulation in arteries, promoting foam cell formation and inflammation. Low levels of HDL may associate with reduced cholesterol efflux from foam cells, aggravating atherosclerosis. While fibrates and fish oils reduce TRL, they have not been uniformly successful in reducing CVD, and there is a large unmet need for new approaches to reduce remnants and CVD. Rare genetic variants that lower triglyceride levels via activation of lipolysis and associate with reduced CVD suggest new approaches to treating dyslipidemia. Apolipoprotein C3 (APOC3) and angiopoietin-like 3 (ANGPTL3) have emerged as targets for inhibition by antibody, antisense, or RNAi approaches. Inhibition of either molecule lowers TRL but respectively raises or lowers HDL levels. Large clinical trials of such agents in patients with high CVD risk and elevated levels of TRL will be required to demonstrate efficacy of these approaches.

Background The American Heart Association (AHA) has recently introduced the concept of Cardiovascular-Kidney-Metabolic (CKM) syndrome, which is the result of an increasing emphasis on the interplay of metabolic, renal and cardiovascular diseases (CVD). Furthermore, there is substantial evidence of a correlation between the triglyceride glucose-body mass index (TyG-BMI ) and CVD as an assessment of insulin resistance (IR). However, it remains unknown whether this correlation exists in population with CKM syndrome. Methods All data for this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS). The exposure was the participants’ TyG-BMI at baseline, which was calculated using a combination of triglycerides (TG), fasting blood glucose (FBG) and body mass index (BMI). The primary outcome was CVD, which were determined by the use of a standardised questionnaire during follow-up. To examine the relationship between TyG-BMI and CVD incidence in population with CKM syndrome, both Cox regression analyses and restricted cubic spline (RCS) regression analyses were performed. Results A total of 7376 participants were included in the final analysis. Of these, 1139, 1515, 1839, and 2883 were in CKM syndrome stages 0, 1, 2, and 3, respectively, at baseline. The gender distribution was 52.62% female, and the mean age was 59.17 ± 9.28 (years). The results of the fully adjusted COX regression analyses indicated that there was a 6.5% increase in the risk of developing CVD for each 10-unit increase in TyG-BMI,95% confidence interval (CI):1.041–1.090. The RCS regression analyses demonstrated a positive linear association between TyG-BMI and the incidence of CVD in the CKM syndrome population (P for overall < 0.001, P for nonlinear = 0.355). Conclusions This cohort study demonstrated a positive linear association between TyG-BMI index and increased CVD incidence in a population with CKM syndrome stage 0–3. This finding suggests that enhanced assessment of TyG-BMI index may provide a more convenient and effective tool for individuals at risk for CVD in CKM syndrome stage 0–3.

The aim of this study was to examine sex disparity in metabolic syndrome prevalence and its risk factors among Chinese adults. Using the 2010-2012 China National Nutrition and Health Survey (CNNHS), a nationally representative cross-sectional study on nutrition and non-communicable chronic diseases, a total of 98,042 participants aged 18 years and older were included in the analysis. Dietary information was collected with a food frequency questionnaire (FFQ). Metabolic syndrome was defined according to the updated NCEP ATP III criteria. A multivariable logistic regression model was performed to examine the associations between sociodemographic and dietary factors with metabolic syndrome prevalence, and the results are presented using odd ratios (ORs) and 95% confidence intervals (CIs). The overall standardized prevalence of metabolic syndrome was 24.2% (24.6% in men and 23.8% in women). The metabolic syndrome prevalence was positively associated with age in men and women. The prevalence of metabolic syndrome was negatively associated with the physical activity level among men and inversely associated with the education level among women (P for trend < 0.01). Frequent consumption of fungi and algae was an underlying risk factor for metabolic syndrome in men, whereas frequent consumption of nuts and pork was associated with a decreased prevalence of metabolic syndrome in women. The prevalence of metabolic syndrome in men was not different from that in women. There are sex-specific associations between multiple risk factors and metabolic syndrome.

Background The prevalence of obesity-associated insulin resistance (IR) is increasing along with the increase in obesity rates. In this study, we compared the predictive utility of four alternative indexes of IR [triglyceride glucose index (TyG index), metabolic score for insulin resistance (METS-IR), the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and homeostatic model assessment of insulin resistance (HOMA-IR)] for all-cause mortality and cardiovascular mortality in the general population based on key variables screened by the Boruta algorithm. The aim was to find the best replacement index of IR. Methods In this study, 14,653 participants were screened from the National Health and Nutrition Examination Survey (2001–2018). And TyG index, METS-IR, TG/HDL-C and HOMA-IR were calculated separately for each participant according to the given formula. The predictive values of IR replacement indexes for all-cause mortality and cardiovascular mortality in the general population were assessed. Results Over a median follow-up period of 116 months, a total of 2085 (10.23%) all-cause deaths and 549 (2.61%) cardiovascular disease (CVD) related deaths were recorded. Multivariate Cox regression and restricted cubic splines analysis showed that among the four indexes, only METS-IR was significantly associated with both all-cause and CVD mortality, and both showed non-linear associations with an approximate “U-shape”. Specifically, baseline METS-IR lower than the inflection point (41.33) was negatively associated with mortality [hazard ratio (HR) 0.972, 95% CI 0.950–0.997 for all-cause mortality]. In contrast, baseline METS-IR higher than the inflection point (41.33) was positively associated with mortality (HR 1.019, 95% CI 1.011–1.026 for all-cause mortality and HR 1.028, 95% CI 1.014–1.043 for CVD mortality). We further stratified the METS-IR and showed that significant associations between METS-IR levels and all-cause and cardiovascular mortality were predominantly present in the nonelderly population aged < 65 years. Conclusions In conjunction with the results of the Boruta algorithm, METS-IR demonstrated a more significant association with all-cause and cardiovascular mortality in the U.S. population compared to the other three alternative IR indexes (TyG index, TG/HDL-C and HOMA-IR), particularly evident in individuals under 65 years old.

Background Triglyceride-glucose (TyG) index has been determined to play a role in the onset of metabolic syndrome (MetS). Whether the TyG index and TyG with the combination of obesity indicators are associated with the clinical outcomes of the MetS population remains unknown. Method Participants were extracted from multiple cycles of the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 years. Three indicators were constructed including TyG index, TyG combining with waist circumference (TyG-WC), and TyG combining with waist-to-height ratio (TyG-WHtR). The MetS was defined according to the National Cholesterol Education Program (NCPE) Adult Treatment Panel III. Kaplan-Meier (KM) curves, restricted cubic splines (RCS), and the Cox proportional hazard model were used to evaluate the associations between TyG-related indices and mortality of the MetS population. The sensitive analyses were performed to check the robustness of the main findings. Results There were 10,734 participants with MetS included in this study, with 5,570 females and 5,164 males. The median age of the study population was 59 years old. The multivariate Cox regression analyses showed high levels of TyG-related indices were significantly associated with the all-cause mortality of MetS population [TyG index: adjusted hazard ratio (aHR): 1.36, 95%confidence interval (CI): 1.18–1.56, p  < 0.001; TyG-WHtR index: aHR = 1.29, 95%CI: 1.13–1.47, p  < 0.001]. Meanwhile, the TyG-WC and TyG-WHtR index were associated with cardiovascular mortality of the MetS population (TyG-WC: aHR = 1.45, 95%CI: 1.13–1.85, p  = 0.004; TyG-WHtR: aHR = 1.50 95%CI: 1.17–1.92, p  = 0.002). Three TyG-related indices showed consistent significant correlations with diabetes mortality (TyG: aHR = 4.06, 95%CI: 2.81–5.87, p  < 0.001; TyG-WC: aHR = 2.55, 95%CI: 1.82–3.58, p  < 0.001; TyG-WHtR: aHR = 2.53 95%CI: 1.81–3.54, p  < 0.001). The RCS curves showed a non-linear trend between TyG and TyG-WC indices with all-cause mortality (p for nonlinearity = 0.004 and 0.001, respectively). The sensitive analyses supported the positive correlations between TyG-related indices with mortality of the MetS population. Conclusion Our study highlights the clinical value of TyG-related indices in predicting the survival of the MetS population. TyG-related indices would be the surrogate biomarkers for the follow-up of the MetS population.

Objective: To estimate the prevalence of the metabolic syndrome (MetS) using reference standards obtained in European children and to develop a quantitative MetS score and describe its distribution in children. Design and methods: Population-based survey in eight European countries, including 18745 children 2.0 to 10.9 years, recruited during a second survey. Anthropometry (weight, height and waist circumference), blood pressure and serum-fasting triglycerides, HDL cholesterol, glucose and insulin were measured. We applied three widely accepted definitions of the pediatric MetS and we suggest a new definition, to guide pediatricians in decisions about close monitoring or even intervention (values of at least three of the MetS components exceeding the 90th or 95th percentile, respectively). We used a z -score standardisation to calculate a continuous score combining the MetS components. Results: Among the various definitions of MetS, the highest prevalence (5.5%) was obtained with our new definition requiring close observation (monitoring level). Our more conservative definition, requiring pediatric intervention gives a prevalence of 1.8%. In general, prevalences were higher in girls than in boys. The prevalence of metabolic syndrome is highest among obese children. All definitions classify a small percentage of thin or normal weight children as being affected. The metabolic syndrome score shows a positive trend with age, particularly regarding the upper percentiles of the score. Conclusions: According to different definitions of pediatric MetS, a non-negligible proportion of mostly prepubertal children are classified as affected. We propose a new definition of MetS that should improve clinical guidance. The continuous score developed may also serve as a useful tool in pediatric obesity research. It has to be noted, however, that the proposed cutoffs are based on a statistical definition that does not yet allow to quantify the risk of subsequent disease.