Pretreatment Prevotella-to-Bacteroides ratio and salivary amylase gene copy number as prognostic markers for dietary weight loss.

BACKGROUND: The inconsistent link observed between salivary amylase gene copy number (AMY1 CN) and weight management is likely modified by diet and microbiome. OBJECTIVE: Based on analysis of a previously published study, we investigated the hypothesis that interaction between diet, Prevotella-to-Bacteriodes ratio (P/B ratio), and AMY1 CN influence weight change. METHODS: Sixty-two people with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in dietary fiber, whole grain, intrinsic sugars, and starch or an Average Danish (Western) Diet (ADD) for 26 weeks. All foods were provided free of charge. Before subjects were randomly assigned to receive the NND or ADD diet, blood and fecal samples were collected, from which AMY1 CN and P/B ratio, respectively, were determined. Body weight change was described by using linear mixed models, including biomarker [log10(P/B ratio) and/or AMY1 CN] diet-group interactions. RESULTS: Baseline means ± SDs of log10(P/B ratio) and AMY1 CN were -2.1 ± 1.8 and 6.6 ± 2.4, respectively. Baseline P/B ratio predicted a 0.99-kg/unit (95% CI: 0.40, 1.57; n = 54; P < 0.001) higher weight loss for those subjects on the NND compared with those on the ADD diet, whereas AMY1 CN was not found to predict weight loss differences between the NND and ADD groups [0.05 kg/CN (95% CI: -0.40, 0.51; n = 54; P = 0.83)]. However, among subjects with low AMY1 CN (<6.5 copies), baseline P/B ratio predicted a 2.12-kg/unit (95% CI: 1.37, 2.88; n = 30; P < 0.001) higher weight loss for the NND group than the ADD group. No such differences in weight loss were found among subjects in both groups with high AMY1 CN [-0.17 kg/unit (95% CI: -1.01, 0.66; n = 24; P = 0.68)]. CONCLUSIONS: The combined use of low AMY1 CN and pretreatment P/B ratio for weight loss prediction led to highly individualized weight loss results with the introduction of more fiber, whole grain, intrinsic sugars, and starch in the diet. These preliminary observations suggest that more undigested starch reaches the colon in individuals with low AMY1 CN, and that the fate of this starch depends on the gut microbiota composition. This trial was registered at clinicaltrials.gov as NCT01195610.

Body mass index is independently associated with xanthine oxidase activity in overweight/obese population.

PURPOSE: The pathophysiological mechanism of the relationship between xanthine oxidase (XO) activity and obesity has not been completely elucidated. Since inflammation and oxidative stress are regarded as key determinants of enlarged adipose tissue, we aimed to investigate the association between oxidative stress (as measured with XO activity), inflammation [as measured with high-sensitivity C-reactive protein (hsCRP)] and obesity [as measured with body mass index (BMI)]. In addition, we wanted to examine whether hsCRP itself plays an independent role in XO activity increase or it is only mediated through obesity. METHODS: A total of 118 overweight/obese volunteers (mean age 54.76 ± 15.13 years) were included in the current cross-sectional study. Anthropometric, biochemical parameters, and blood pressure were obtained. RESULTS: Significant differences between age, BMI, waist circumference, concentrations of uric acid and hsCRP, as well as xanthine dehydrogenase (XDH) activities were evident among XO tertile groups. Multiple linear regression analysis revealed that BMI (beta = 0.241, p = 0.012) and XDH (beta = - 0.489, p < 0.001) are the independent predictors of XO activity (R2-adjusted = 0.333), whereas hsCRP lost its independent role in XO activity prediction. CONCLUSION: Obesity (as determined with increased BMI) is an independent predictor of high XO activity in overweight/obese population. LEVEL OF EVIDENCE: Level V: cross-sectional descriptive study.

Efficacy and Safety of Firibastat, A First-in-Class Brain Aminopeptidase A Inhibitor, in Hypertensive Overweight Patients of Multiple Ethnic Origins.

BACKGROUND: Despite existing therapy, successful control of hypertension in the United States is estimated at less than 50%. In blacks, hypertension occurs earlier, is more severe, controlled less often and has a higher morbidity and mortality than in whites. Blacks are also less responsive to monotherapy with angiotensin-I converting enzyme inhibitors or angiotensin-II receptor type 1 blockers. Obesity, higher salt-sensitivity and low plasma renin activity are possible reasons of this poor blood pressure (BP) control, especially in blacks. The aim of the study was to assess efficacy and safety of firibastat, a first-in-class aminopeptidase A inhibitor preventing conversion of brain angiotensin-II into angiotensin-III, in BP lowering in a high-risk diverse hypertensive population. METHODS: Two hundred fifty-six overweight or obese hypertensive patients, including 54% black and Hispanic individuals, were enrolled in a multicenter, open-label, phase II study. After a 2-week wash-out period, subjects received firibastat for 8 weeks (250 mg BID orally for 2 weeks, then 500 mg BID if automated office blood pressure (AOBP) >140/90 mm Hg; hydrochlorothiazide 25 mg QD was added after 1 month if AOBP ≥160/110 mm Hg). The primary end point was change from baseline in systolic AOBP after 8 weeks of treatment, and secondary end points include diastolic AOBP, 24-hour mean ambulatory BP and safety. RESULTS: Firibastat lowered systolic AOBP by 9.5 mm Hg ( P<0.0001) and diastolic AOBP by 4.2 mm Hg ( P<0.0001). 85% of the subjects did not receive hydrochlorothiazide and were treated with firibastat alone. Significant BP reduction was found across all subgroups regardless age, sex, body mass index, or race. Systolic AOBP decreased by 10.2 mm Hg ( P<0.0001) in obese patients, by 10.5 mm Hg ( P<0.0001) in blacks, and 8.9 mm Hg ( P<0.0001) in nonblacks. Most frequent adverse events were headaches (4%) and skin reactions (3%). No angioedema was reported. No change in potassium, sodium, and creatinine blood level were observed. CONCLUSIONS: Our results demonstrate the efficacy of firibastat in lowering BP in a high-risk diverse population where monotherapy with angiotensin-I converting enzyme inhibitors or angiotensin-II receptor type 1 blockers may be less effective and support the strategy to further investigate firibastat in subjects with difficult-to-treat or potentially resistant hypertension. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique Identifier: NCT03198793.

Predictors of obesity and overweight in preschoolers: The role of parenting styles and feeding practices.

Childhood obesity/overweight (OB/OW) displayed a rapid increase and high prevalence in the last few decades in preschool-aged children, which raised health concerns across the world and motivated researchers to investigate the factors that underlie childhood obesity. The current study examined parenting styles and child-feeding practices as potential predictors for OB/OW in preschool children, controlling for child's temperament, which has been shown to be linked with OB/OW. The sample included 61 normal weight (NW) and 61 obese/overweight (OB/OW) Turkish pre-schoolers (M age = 62.2 months; SD = 7.64, range = 45-80 months). Parenting styles (authoritarian, authoritative), child-feeding practices (restriction, pressure to eat, monitoring), and child's temperament (negative affectivity) were measured with mothers' reports. Results showed that authoritarian parenting and maternal pressure to eat were the two parenting variables that significantly predicted child's weight status; the odds of being OB/OW was 4.71 times higher in children whose mothers used higher authoritarian parenting style, and was 0.44 times lower when mothers pressured their child to eat. These findings suggest that understanding the unique role of different aspects of parenting in the risk of early OB/OW status of children would be important in developing more effective interventions from early years in life.

Correlations of Complete Blood Count with Alanine and Aspartate Transaminase in Chinese Subjects and Prediction Based on Back-Propagation Artificial Neural Network (BP-ANN).

BACKGROUND The complete blood count (CBC) is the most common examination used to monitor overall health in clinical practice. Whether there is a relationship between CBC indexes and alanine transaminase (ALT) and aspartate aminotransferase (AST) has been unclear. MATERIAL AND METHODS In this study, 572 normal-weight and 346 overweight Chinese subjects were recruited. The relationship between CBC indexes with ALT and AST were analyzed by Pearson and Spearman correlations according to their sex, then we conducted colinearity diagnostics and multiple linear regression (MLR) analysis. A prediction model was developed by a back-propagation artificial neural network (BP-ANN). RESULTS ALT was related to 4 CBC indexes in the male normal-weight group and 3 CBC indexes in the female group. In the overweight group, ALT had a similar relationship with the normal group, but there was only 1 index related with AST in the normal-weight group and male overweight groups. The ALT regression models were developed in normal-weight and overweight people, which had better correlation coefficient (R>0.3). After training 1000 epochs, the BP-ANN models of ALT achieved higher correlations than MLR models in normal-weight and overweight people. CONCLUSIONS ALT is a more suitable index than AST for developing a regression model. ALT can be predicted by CBC indexes in normal-weight and overweight individuals based on a BP-ANN model, which was better than MLR analysis.

Paraoxonase-1 and myeloperoxidase correlate with vascular biomarkers in overweight patients with newly diagnosed untreated hyperlipidaemia.

BACKGROUND: In hyperlipidaemic state, increased levels of myeloperoxidase (MPO) and decreased paraoxonase-1 (PON1) activity have been reported; however, their relationships with other atherosclerotic biomarkers have not been completely clarified. PATIENTS AND METHODS: Serum concentrations of lipid and inflammatory parameters, MPO levels, and PON1 activities were investigated in 167 untreated hyperlipidaemic patients with and without vascular complications and in 32 healthy controls. Additionally, levels of CD40 ligand (sCD40L) and asymmetric dimethyl arginine (ADMA), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1, and oxidized LDL were determined. RESULTS: We found elevated C-reactive protein (CRP), ADMA, sCD40L, sICAM-1 concentrations, and higher MPO levels in patients with vascular complications compared to those without. The PON1 arylesterase activity correlated negatively with sCD40L, ADMA, and sICAM-1 levels, respectively. In contrast, MPO concentrations showed positive correlations with sCD40L, ADMA, and sICAM-1 levels, respectively. CONCLUSIONS: It can therefore be stated that PON1 activity and MPO level correlate strongly with the vascular biomarkers, highlighting the importance of the HDL-associated pro- and antioxidant enzymes in the development of endothelial dysfunction and atherogenesis.

Impact of Liraglutide on Amylase, Lipase, and Acute Pancreatitis in Participants With Overweight/Obesity and Normoglycemia, Prediabetes, or Type 2 Diabetes: Secondary Analyses of Pooled Data From the SCALE Clinical Development Program.

OBJECTIVE: To describe amylase/lipase activity levels and events of acute pancreatitis (AP) in the SCALE (Satiety and Clinical Adiposity-Liraglutide Evidence in individuals with and without diabetes) weight-management trials. RESEARCH DESIGN AND METHODS: Secondary analyses were performed on pooled data from four trials (N = 5,358 with BMI ≥30, or 27 to <30 kg/m2 with ≥1 comorbidity). Of these, 1,723 had normoglycemia, 2,789 had prediabetes, and 846 had type 2 diabetes. Participants were randomized to liraglutide 3.0 mg (n = 3,302), liraglutide 1.8 mg (n = 211, only type 2 diabetes), or placebo (n = 1,845). Relationships between baseline characteristics and amylase/lipase activity at baseline and during treatment were investigated. RESULTS: Over 56 weeks, liraglutide 3.0 mg versus placebo was associated with increases in mean levels of 7% (amylase) and 31% (lipase), respectively. Similar changes in amylase/lipase levels were observed with liraglutide 1.8 mg. More participants receiving liraglutide 3.0 mg versus placebo experienced amylase (9.4% vs. 5.9%) and lipase (43.5% vs. 15.1%) elevations greater than or equal to the upper limit of normal (ULN); few had elevations ≥3 × ULN for amylase (<0.1% with liraglutide 3.0 mg or placebo) or lipase (2.9% vs. 1.5%, respectively). After liraglutide discontinuation, enzymes returned to baseline levels. Thirteen participants developed AP: 12 on (n = 9, 0.3%) or after (n = 3, 0.1%) liraglutide 3.0 mg treatment and one (0.1%) with placebo. A total of 6/13 participants with AP (5/12 liraglutide; 1 placebo) had gallstone disease evident at AP onset. Amylase/lipase elevations either 1 × ULN or ≥3 × ULN before AP onset had very low positive predictive value for AP (<1%). CONCLUSIONS: Liraglutide resulted in dose-independent, reversible increases in amylase/lipase activity, unrelated to baseline characteristics, not predicting AP onset. Gallstones possibly contributed to 50% of AP cases. Data provide no basis for amylase/lipase level monitoring in liraglutide treatment except in suspected AP.

Opposite effects of a glucokinase activator and metformin on glucose-regulated gene expression in hepatocytes.

AIM: Small molecule activators of glucokinase (GKAs) have been explored extensively as potential anti-hyperglycaemic drugs for type 2 diabetes (T2D). Several GKAs were remarkably effective in lowering blood glucose during early therapy but then lost their glycaemic efficacy chronically during clinical trials. MATERIALS AND METHODS: We used rat hepatocytes to test the hypothesis that GKAs raise hepatocyte glucose 6-phosphate (G6P, the glucokinase product) and down-stream metabolites with consequent repression of the liver glucokinase gene ( Gck). We compared a GKA with metformin, the most widely prescribed drug for T2D. RESULTS: Treatment of hepatocytes with 25 mM glucose raised cell G6P, concomitantly with Gck repression and induction of G6pc (glucose 6-phosphatase) and Pklr (pyruvate kinase). A GKA mimicked high glucose by raising G6P and fructose-2,6-bisphosphate, a regulatory metabolite, causing a left-shift in glucose responsiveness on gene regulation. Fructose, like the GKA, repressed Gck but modestly induced G6pc. 2-Deoxyglucose, which is phosphorylated by glucokinase but not further metabolized caused Gck repression but not G6pc induction, implicating the glucokinase product in Gck repression. Metformin counteracted the effect of high glucose on the elevated G6P and fructose 2,6-bisphosphate and on Gck repression, recruitment of Mlx-ChREBP to the G6pc and Pklr promoters and induction of these genes. CONCLUSIONS: Elevation in hepatocyte G6P and downstream metabolites, with consequent liver Gck repression, is a potential contributing mechanism to the loss of GKA efficacy during chronic therapy. Cell metformin loads within the therapeutic range attenuate the effect of high glucose on G6P and on glucose-regulated gene expression.

Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults.

There is scarce information about the link between specific single-nucleotide polymorphisms (SNPs) and risk of liver disease among Latinos, despite the disproportionate burden of disease among this population. Our aim was to investigate nine SNPs in or near the following genes: PNPLA3, LYPLAL1, PPP1R3B, GCKR, NCAN, IRS1, PPARG, and ADIPOR2 and examine their association with persistently elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels in Mexican adults. Data and samples were collected from 741 participants in the Mexican Health Worker Cohort Study, in Cuernavaca, Mexico. We identified 207 cases who had persistently elevated levels of ALT or AST (≥40 U/L) and 534 controls with at least two consecutive normal ALT or AST results in a 6 month period, during 2004-2006 and 2011-2013. TaqMan assays were used to genotype the SNPs. The risk allele of PNPLA3 rs738409 was found to be associated with persistently elevated levels of ALT or AST, adjusting for age, sex, BMI, type 2 diabetes, and ancestry: (OR 2.28, 95 % CI 1.13, 4.58). A significant association was found between the LYPLAL1, PPP1R3B, and GCKR risk alleles and elevated ALT or AST levels among overweight/obese adults. These results suggest that among Mexicans, the PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) polymorphisms may be associated with a greater risk of chronic liver disease among overweight adults. This study is the first to examine these nine SNPs in a sample of adults in Mexico.

Relation between Liver Transaminases and Dyslipidaemia among 2-10 y.o. Northern Mexican Children.

BACKGROUND AND AIMS: The increase in overweight and obese children may be linked to increased rates of liver damage and dyslipidaemia. This study aimed to explore the associations of liver biomarkers with overweight/obesity and dyslipidaemia in Mexican children. METHODS: The study was a population-based cross-sectional nutritional survey carried out in the State of Nuevo León, Mexico. The study included a 414 subjects aged between 2 and 10 years old (47.8% girls) who took part in the State Survey of Nutrition and Health-Nuevo León 2011/2012. Associations between alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ALT/AST ratio, and major components of serum lipid profile were assessed. RESULTS: Children with high ALT (defined as ≥P75) showed higher prevalence of dyslipidaemia than their counterparts, with high prevalence of high TChol (P = 0.053), non-HDL-chol, TG, and low HDL-chol. Children with an AST/ALT ≥T3 ratio were 0.43-times (95% CI: 0.25-0.74) and 0.27-times (95% CI: 0.17-0.44) low likely to be overweight/obese and to have dyslipidaemia than those with an AST/ALT

Increased RhoA/Rho-Kinase Activity and Markers of Endothelial Dysfunction in Young Adult Subjects with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome, a chronic condition associated with higher risk of cardiovascular diseases, is increasingly prevalent in young adults. Dyslipidemia, proinflammatory cytokines, endothelial dysfunction signs, and RhoA/Rho-kinase (ROCK) activation are considered risk factors of cardiovascular diseases. The occurrence of these factors in young patients with metabolic syndrome but without type 2 diabetes or hypertension has not been fully studied. The objective of this study was to evaluate young subjects with enlarged waist circumference and dyslipidemia but without type 2 diabetes or hypertension,for markers associated with a higher risk of cardiovascular diseases. METHODS: Thirty-two male patients aged 31 ± 1.3 years diagnosed with metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III guide for enlarged waist circumference, elevated triglycerides, and low HDL levels, but with blood pressure and fasting glucose within normal ranges, were evaluated for RhoA/ROCK activity in leukocytes, serum fatty acid methyl esters profile, proinflammatory cytokines, and oxidative stress markers in addition to thrombin generation and biochemical analysis. Age- and gender-matched healthy subjects were equivalently evaluated. RESULTS: Patients showed higher RhoA/ROCK activity, elevated levels of interleukin-6, soluble CD40L, monocyte chemoattractant protein, and high-sensitivity C-reactive protein (P < 0.001) as well as parameters of endogenous thrombin generation potential (P < 0.05) compared with healthy subjects. Increased thiobarbituric acid reactive substances, advanced oxidation protein product, and insulin levels and low nitric oxide biodisponibility (P < 0.001) were also found in patients as compared with controls. Palmitic acid was one of the saturated fatty acids found to be significantly elevated in patients compared with control subjects (P = 0.0087). CONCLUSIONS: Increased markers of cardiovascular risk are already present in young adults with metabolic syndrome but without type 2 diabetes or hypertension.

Waist-to-height ratio is more closely associated with alanine aminotransferase levels than body mass index and waist circumference among population-based children: a cross-sectional study in Japan.

BACKGROUND: An association between anthropometric measurements, including waist circumference (WC), and alanine aminotransferase (ALT) levels has been reported among adults. However, studies conducted among population-based elementary schoolchildren to date have been limited, especially in Japan, where the measurement of WC and blood collection are not usually performed in the annual health examination at elementary schools. The present study investigated the association between anthropometric measurements and ALT levels among population-based elementary schoolchildren in Japan. METHODS: Subjects were fourth-grade schoolchildren (aged 9 or 10) from the town of Ina in Saitama Prefecture, Japan during 2004-2009. The height, weight, and WC of each subject were measured, and blood samples were drawn to measure ALT levels. Childhood overweight or obesity was defined according to the age- and sex-specific cut-off points proposed by the International Obesity Task Force. Spearman's correlation coefficients between anthropometric measurements (body mass index (BMI), WC, and waist-to-height ratio (WHtR)) and ALT levels were calculated. RESULTS: Data from 2499 subjects (1293 boys and 1206 girls) were analyzed. BMI, WC, and WHtR were significantly positively correlated with ALT levels; the correlation coefficient of ALT levels with WHtR was higher than that with BMI and WC in boys and girls. In the analysis stratified by physique (non-overweight/obesity, overweight, or obesity), all anthropometric measurements were significantly positively correlated with ALT levels among boys, while only WHtR was significantly positively correlated with ALT levels among girls. Moreover, the correlation coefficient of ALT levels with WHtR was more pronounced than that with BMI and WC in the non-overweight/obesity group, in the overweight group, and in the obesity group for each sex. CONCLUSIONS: The present study showed that WHtR was more closely associated with ALT levels than BMI and WC. Furthermore, only WHtR was significantly positively associated with ALT levels regardless of sex and physique. This study suggests that it is more useful to monitor WHtR than BMI and WC as a surrogate for ALT levels among population-based elementary schoolchildren.

Long-chain polyunsaturated fatty acid status in obesity: a systematic review and meta-analysis.

Long-chain polyunsaturated fatty acid (LCPUFA) status has recently been related to the pathogenesis of obesity. Our aims were to systematically review observational studies investigating LCPUFA status from different blood compartments in overweight or obese subjects and to assess the relationship between LCPUFA profile and obesity. The Ovid MEDLINE, Scopus and Cochrane Library CENTRAL databases were searched from inception to January 2014. The meta-analysis showed significant differences in the LCPUFA composition of total plasma lipids, plasma phospholipids and plasma cholesteryl esters between overweight or obese subjects and controls. Dihomo-γ-linolenic acid (DGLA) values were significantly higher in overweight or obese subjects compared with controls in all the investigated biomarkers. In addition, the DGLA/linoleic acid ratio (surrogate parameter for Δ6 desaturase activity) in plasma phospholipids was significantly elevated (mean difference [MD]: 0.05; 95% confidence interval [CI]: 0.02, 0.08; n = 280), while the arachidonic acid/DGLA ratio (surrogate parameter for Δ5 desaturase activity) was significantly decreased (MD: -0.55; 95% CI: -0.71, -0.39; n = 347) in overweight or obese subjects compared with controls. The results of the present meta-analysis confirm that LCPUFA profile is altered in obesity and suggest that the differences observed in desaturase activities may be responsible for the disturbed LCPUFA metabolism in obesity.

An active lifestyle induces positive antioxidant enzyme modulation in peripheral blood mononuclear cells of overweight/obese postmenopausal women.

AIMS: The aim of this study was to investigate the effects of an active lifestyle on mitochondrial functioning, viability, bioenergetics, and redox status markers in peripheral blood mononuclear cells (PBMC) of overweight/ obese postmenopausal women. MATERIALS AND METHODS: We performed a cross-sectional study with postmenopausal women aged 45­64 years and body mass index N 25 kg/m2, divided into physically active (n = 23) and sedentary (n = 12) groups. Mitochondria functioning and viability, bioenergetics and redox status parameters were assessed in PBMC with spectrophotometric and fluorometric assays. KEY FINDINGS: No differences were found in the enzyme activity of complexes I and II of the electron transport chain (ETC), mitochondrial superoxide dismutase (MnSOD) activity, methyl-tetrazolium reduction levels and reduced glutathione and oxidized glutathione levels between the groups. However, the physically active group presented higher levels of reactive oxygen species (ROS) (P= 0.04) and increased catalase (CAT) (P= 0.029), total (P= 0.011) and cytosolic SOD (CuZnSOD) (P= 0.009) activities. SIGNIFICANCE: An active lifestyle that includes aerobic exercise for at least 30 min, three times per week may improve antioxidant enzyme activities in PBMC in overweight/obese postmenopausal women, without changes in the activity of the ETC enzymes. However, this low intensity physical activity is not able to induce relevant mitochondrial adaptations.

Serum alanine aminotransferase predicts interventricular septum thickness and left ventricular mass in patients with nonalcoholic fatty liver disease.

BACKGROUND: Alanine aminotransferase (ALT) is a marker of nonalcoholic fatty liver disease (NAFLD) and predicts type 2 diabetes mellitus (DM2) as well as coronary events independently of traditional risk factors and the features of the metabolic syndrome. The extent to which interventricular septum thickness (IVS) and left ventricular mass (LVM) are associated with ALT levels in cohorts of individuals with body weights ranging from overweight to morbid obesity and NAFLD remains still unknown. MATERIALS AND METHODS: This was a cross-sectional pilot study involving 151 young White participants with liver ultrasound-proven NAFLD. Standard echocardiograms were used to define LVM, IVS, and left ventricle diastolic function [mitral inflow velocity pattern (E/A ratio) and mitral annulus velocity by tissue Doppler imaging (Em/Am ratio)]. Participants were classified according to ALT quartiles: p25, p50, p75, and p100. RESULTS: The study included 36 men and 115 women with an age of 38.4 ± 0.7 years and BMI of 43.9 ± 0.6 kg/m2. p100 participants disclosed significantly higher homeostasis model assessment (P=0.003), DM2 (P=0.002), and hypertension (P=0.01) prevalence, whereas LVM, IVS, E/A, and Em/Am ratios were significantly higher in this group when compared with their p25 peers (P<0.01). IVS's and LVM's variance were significantly predicted by the statistical models including ALT independently of BMI, hypertension, and DM2. CONCLUSION: ALT levels predict both IVS and LVM in NAFLD individuals irrespective of their BMI, DM2, hypertension, age, and sex. ALT levels behave as a surrogate marker of left ventricular hypertrophy in overweight and/or obese NAFLD patients. Hence, it seems worth obtaining cardiac ultrasounds in NAFLD patients with elevated ALT levels.

Role of SN1 lipases on plasma lipids in metabolic syndrome and obesity.

OBJECTIVE: To assess the phospholipase activity of endothelial (EL) and hepatic lipase (HL) in postheparin plasma of subjects with metabolic syndrome (MS)/obesity and their relationship with atherogenic and antiatherogenic lipoproteins. Additionally, to evaluate lipoprotein lipase (LPL) and HL activity as triglyceride (TG)-hydrolyses to complete the analyses of SN1 lipolytic enzymes in the same patient. APPROACH AND RESULTS: Plasma EL, HL, and LPL activities were evaluated in 59 patients with MS and 36 controls. A trend toward higher EL activity was observed in MS. EL activity was increased in obese compared with normal weight group (P=0.009) and was negatively associated with high-density lipoprotein-cholesterol (P=0.014 and P=0.005) and apolipoprotein A-I (P=0.045 and P=0.001) in control and MS group, respectively. HL activity, as TG-hydrolase, was increased in MS (P=0.025) as well as in obese group (P=0.017); directly correlated with low-density lipoprotein-cholesterol (P=0.005) and apolipoprotein B (P=0.003) and negatively with high-density lipoprotein-cholesterol (P=0.021) in control group. LPL was decreased in MS (P<0.001) as well as in overweight and obese compared with normal weight group (P=0.015 and P=0.004, respectively); inversely correlated %TG-very low-density lipoproteins (P=0.04) and TG/apolipoprotein B index (P=0.013) in control group. These associations were not found in MS. CONCLUSIONS: We describe for the first time EL and HL activity as phospholipases in MS/obesity, being both responsible for high-density lipoprotein catabolism. Our results elucidate part of the remaining controversies about SN1 lipases activity in MS and different grades of obesity. The impact of insulin resistance on the activity of the 3 enzymes determines the lipoprotein alterations observed in these states.

Increased levels of circulating arginase I in overweight compared to normal weight adolescents.

BACKGROUND AND AIMS: Overweight and the metabolic syndrome have become major problems, especially in children and adolescents. Obesity at a young age increases the risk for cardiovascular diseases and diabetes mellitus later in life. An early event in the development of cardiovascular disease is endothelial dysfunction which is found in obese young individuals. Increased activity of the enzyme arginase has been described as a central mechanism for endothelial dysfunction, especially in patients with diabetes mellitus. The aim of the study was to determine plasma levels of arginase in overweight adolescents. METHODS: Sixty-six male German adolescents (age: 15.2 ± 1.1 years old) were included. Thirty-one of them were overweight (>90th age-specific weight percentile). Plasma arginase I and tumor necrosis factor alpha (TNFα) were determined. In addition, clinical data were recorded and anthropometrical measurements of obesity were performed. RESULTS: Overweight adolescents had a higher systolic blood pressure, lower high-density lipoprotein and increased levels of high-sensitive C-reactive protein (CRP). Circulating arginase I was elevated in overweight adolescents (95.8 ± 68.2 ng/ml) compared to normal weight adolescents (39.3 ± 26.9 ng/ml, p < 0.001) and correlated with markers of obesity. There was no difference between the two groups regarding TNFα. CONCLUSIONS: We demonstrate that arginase I levels are increased in obese adolescents. Knowing the important role for arginase in endothelial dysfunction, elevated levels of arginase I may represent a link between obesity, endothelial dysfunction and related comorbidities.

Prevalence and predictors of alanine aminotransferase elevation among normal weight, overweight and obese youth in Mexico.

OBJECTIVE: This study aimed to determine the prevalence of and risk factors associated with elevated alanine aminotransferase (ALT) levels among a sample of normal weight, overweight and obese youth from two urban populations in Central Mexico. METHODS: Baseline data from 1262 youth aged 8-19 years who participated in the Mexican Health Worker Cohort Study from March 2004 to April 2006 were reviewed, including 680 girls and 582 boys, with a total of 83 participants with elevated ALT level (>40 U/L). Information was obtained from self-administered questionnaires, anthropometric results and clinical measurements. Associations of interest were examined using multivariate logistic regression models. RESULTS: A total of 3.8% of girls and 9.8% of boys had elevated ALT levels. Elevated ALT was observed in 28.9% of the obese and 14.2% of the overweight participants. Metabolic syndrome (MS) occurred in 6.1% of the study population and those with MS had a high percentage of elevated ALT (14.5% of girls and 40.0% of boys, respectively). Abdominal obesity and insulin resistance were also associated with a greater risk of elevated ALT. CONCLUSIONS: Obesity and certain metabolic risk factors are important predictors for elevated ALT. Screening for ALT levels in obese youth could help to identify those at risk and reduce the possibility of future liver diseases.

Which liver enzymes are better indicators of metabolic syndrome in adolescents: the Fifth Korea National Health and Nutrition Examination Survey, 2010.

BACKGROUND: This study aimed to examine the relationships of liver enzyme levels with metabolic syndrome in adolescents. METHODS: A total of 808 adolescents (430 males and 378 females, aged 10-19 years) participated in the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1) in 2010, the relationships between liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), ratio of AST to ALT (AST/ALT), and γ-glutamyltransferase (GGT)] and metabolic syndrome defined by the International Diabetes Federation criteria were assessed using logistic regression and receiver operating characteristic (ROC) curve analyses. RESULTS: After adjusting for age, higher ALT and GGT levels and a lower AST/ALT level were associated with clustering of metabolic syndrome components, whereas AST level was not associated with it in both sexes. The strength of association between the liver enzymes and clustering of metabolic syndrome components was higher in females than in males. In the non-overweight group, higher AST, ALT, and GGT levels and a lower AST/ALT level were associated with clustering of metabolic syndrome components, whereas none of the liver enzymes was associated with metabolic syndrome in the overweight group. The area under the ROC curve (AUC) of AST to determine metabolic syndrome was not significant and was significantly lower than AUCs of ALT, AST/ALT, and GGT in both sexes. The cutoff values of ALT, AST/ALT, and GGT to determine metabolic syndrome were higher in males than in females. CONCLUSIONS: ALT, AST/ALT, and GGT were found to be associated with clustering of metabolic syndrome components, and the relationships appear to be sex- and weight group-specific.

Adipocyte fatty acid storage factors enhance subcutaneous fat storage in postmenopausal women.

Increases in weight have been associated with corresponding increases in insulin resistance in postmenopausal women. Although estrogen has significant impact on body fat and body fat distribution, the cellular mechanisms that influence this process are not yet known. We measured adipose tissue fatty acid (FA) storage and FA storage factors in 12 premenopausal and 11 postmenopausal women matched for age and body composition. Postmenopausal women had lower postprandial FA oxidation (indirect calorimetry), greater meal FA, and direct free FA (FFA) storage than premenopausal women, including two-fold greater meal FA storage in the femoral depot. The fed/fasted activities of adipose tissue lipoprotein lipase were not significantly different between premenopausal and postmenopausal women. In contrast, adipocyte acyl-CoA synthetase and diacylglycerol acyltransferase activities in postmenopausal women were significantly upregulated and were positively correlated with direct FFA storage rates. These findings suggest that the propensity for subcutaneous adipose tissue FA storage is increased in postmenopausal women, more so from changes in adipocyte FA storage factors than from adipose tissue lipoprotein lipase activity. Our results suggest that female sex steroids, most likely estrogen, have important effects on adipose tissue FA storage and FA oxidation that could promote fat gain in postmenopausal women.