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Background: Accumulation of saturated fatty acids (SFAs) in the liver is known to induce hepatic steatosis and inflammation causing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Although SFAs have been shown to affect the epigenome in whole blood, pancreatic islets, and adipose tissue in humans, and genome-wide DNA methylation studies have linked epigenetic changes to NAFLD and NASH, studies focusing on the association of SFAs and DNA methylation in human liver are missing. We, therefore, investigated whether human liver SFA content associates with DNA methylation and tested if SFA-linked alterations in DNA methylation associate with NAFLD-related clinical phenotypes in obese individuals. Results: We identified DNA methylation (Infinium HumanMethylation450 BeadChip) of 3169 CpGs to be associated with liver total SFA content (q-value < 0.05) measured using proton NMR spectroscopy in participants of the Kuopio Obesity Surgery Study (n = 51; mean ± SD:49.3 ± 8.5 years old; BMI:43.7 ± 6.2 kg/m2). Of these 3169 sites, 797 overlapped with previously published NASH-associated CpGs (NASH-SFA), while 2372 CpGs were exclusively associated with SFA (Only-SFA). The corresponding annotated genes of these only-SFA CpGs were found to be enriched in pathways linked to satiety and hunger. Among the 54 genes mapping to these enriched pathways, DNA methylation of CpGs mapping to PRKCA and TSPO correlated with their own mRNA expression (HumanHT-12 Expression BeadChip). In addition, DNA methylation of another ten of these CpGs correlated with the mRNA expression of their neighboring genes (p value < 0.05). The proportion of CpGs demonstrating a correlation of DNA methylation with plasma glucose was higher in NASH-SFA and only-SFA groups, while the proportion of significant correlations with plasma insulin was higher in only-NASH and NASH-SFA groups as compared to all CpGs on the Illumina 450 K array (Illumina, San Diego, CA, USA). Conclusions: Our results suggest that one of the mechanisms how SFA could contribute to metabolic dysregulation in NAFLD is at the level of DNA methylation. We further propose that liver SFA-related DNA methylation profile may contribute more to hyperglycemia, while insulin-related methylation profile is more linked to NAFLD or NASH. Further research is needed to elucidate the molecular mechanisms behind these observations. [ABSTRACT FROM AUTHOR]

Background: Endocan is a soluble dermatan sulfate proteoglycan (50 kDa) secreted by endothelial cells and expressed by dermal, coronary, pulmonary and adipose tissue microvasculature. It plays an important role in the pathogenesis of vascular disorders, inflammatory state, endothelium dysfunction and neoangiogenesis. Aims of the study were to compare fasting serum endocan levels between children with obesity and healthy controls and to investigate the relationships between endocan, body mass index (BMI) and other indices of cardiometabolic risk. Methods: This single-center, observational, retrospective study included 19 pediatric patients with obesity aged 11.94 ± 0.52 years and 19 lean matched controls. Each patient underwent clinical and auxological examination and laboratory investigations including routine organs function tests and lipid profile. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Fasting endocan serum levels were measured using an enzyme-linked immunosorbent assay (ELISA). Results: Compared to healthy subjects, serum endocan levels were found to be significantly upraised in children with obesity. Endocan resulted significantly correlated with insulin levels (rho 0.47; p = 0.04); in addition, an association with HOMA-IR values with a trend toward the statistical significance (rho 0.43; p = 0.07) was found. No significant correlation with fasting blood glucose values and lipid serum levels was demonstrated. Although not statistically significant, a correlation between endocan and the presence and grading of liver steatosis on ultrasound (rho 0.51; p = 0.08 and rho 0.51; p = 0.08, respectively) was found. Conclusions: These findings confirm the association between endothelial damage and insulin resistance in children with obesity. Endocan could be used as a biomarker of early endothelial dysfunction in children with obesity and could be a valid predictor of future cardiovascular risk in adulthood. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress (OS) is associated with a variety of non-communicable diseases, including MetS, diabetes mellitus, metabolic syndrome, and cardiovascular disease through increased production of reactive oxygen species (ROS) and impairment of antioxidant defense mechanisms. Antioxidants can protect cells against free radical damage, so it seems important to determine the relationship between the quality of dietary antioxidants intake and chronic diseases. The Dietary Antioxidant Quality Score (DAQS) is obtained by adding the daily intake of known dietary vitamins and minerals, including selenium, zinc, vitamin A, vitamin C, and vitamin E, compared to the recommended daily intake (RDI). Therefore, this study aims to determine the relationship between DAQS, serum lipids, markers of glucose homeostasis, blood pressure and anthropometric features among obese adults. Methods: In the present cross-sectional study, 338 individuals who were obese (BMI ≥ 30 kg/m2) aged 20-50 years were recruited from Tabriz and Tehran, Iran. A validated semi-quantitative Food Frequency Questionnaire (FFQ) with 168 food items was used to quantify dietary consumption; accordingly, DAQS was computed. Blood biomarkers were measured using enzyme-linked immunosorbent assay (ELISA) kits. A standard mercury sphygmomanometer was used to assess blood pressure, and bioelectrical impedance analysis (BIA) was performed to determine body composition. The association between the DAQS tertiles and biochemical variables was investigated using multinomial logistic regression. Results: Participants in the highest tertile of DAQS have a lower diastolic blood pressure (DBP) values in all of the adjusted models [odds ratio (OR) = 0.920; confidence interval (CI)= 0.852-0.993, P-value = 0.03] in the analysis of co-variance (ANCOVA) model. Similarly, subjects at the second tertile of DAQS had lower DBP compared with the first tertile in age and sex-adjusted model [OR= 0.937; CI= 0.882-0.997]. There was no statistically significant difference for other metabolic parameters in different DAQS tertiles. Conclusion: According to our findings, higher DAQS was associated with lower DBP among obese adults with obesity in two major cities of Iran (Tehran and Tabriz). Other studies with interventional design are needed to better elucidate these associations and underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Accumulation of saturated fatty acids (SFAs) in the liver is known to induce hepatic steatosis and inflammation causing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Although SFAs have been shown to affect the epigenome in whole blood, pancreatic islets, and adipose tissue in humans, and genome-wide DNA methylation studies have linked epigenetic changes to NAFLD and NASH, studies focusing on the association of SFAs and DNA methylation in human liver are missing. We, therefore, investigated whether human liver SFA content associates with DNA methylation and tested if SFA-linked alterations in DNA methylation associate with NAFLD-related clinical phenotypes in obese individuals. Results: We identified DNA methylation (Infinium HumanMethylation450 BeadChip) of 3169 CpGs to be associated with liver total SFA content (q-value < 0.05) measured using proton NMR spectroscopy in participants of the Kuopio Obesity Surgery Study (n = 51; mean ± SD:49.3 ± 8.5 years old; BMI:43.7 ± 6.2 kg/m2). Of these 3169 sites, 797 overlapped with previously published NASH-associated CpGs (NASH-SFA), while 2372 CpGs were exclusively associated with SFA (Only-SFA). The corresponding annotated genes of these only-SFA CpGs were found to be enriched in pathways linked to satiety and hunger. Among the 54 genes mapping to these enriched pathways, DNA methylation of CpGs mapping to PRKCA and TSPO correlated with their own mRNA expression (HumanHT-12 Expression BeadChip). In addition, DNA methylation of another ten of these CpGs correlated with the mRNA expression of their neighboring genes (p value < 0.05). The proportion of CpGs demonstrating a correlation of DNA methylation with plasma glucose was higher in NASH-SFA and only-SFA groups, while the proportion of significant correlations with plasma insulin was higher in only-NASH and NASH-SFA groups as compared to all CpGs on the Illumina 450 K array (Illumina, San Diego, CA, USA). Conclusions: Our results suggest that one of the mechanisms how SFA could contribute to metabolic dysregulation in NAFLD is at the level of DNA methylation. We further propose that liver SFA-related DNA methylation profile may contribute more to hyperglycemia, while insulin-related methylation profile is more linked to NAFLD or NASH. Further research is needed to elucidate the molecular mechanisms behind these observations. [ABSTRACT FROM AUTHOR]

Background: Several previous studies revealed the role of dietary energy density (DED) in developing obesity and related disorders. However, the possible role of DED in triggering cardiometabolic risk factors of individuals with obesity has not been studied yet. This study aimed to evaluate the association between DED and anthropometric parameters, blood pressure, and components of metabolic syndrome (MetS) (such as glycemic markers, lipid profile, and blood pressure) among individuals with obesity. Methods: In this cross-sectional study, we included 335 adults with obesity (BMI ≥ 30 kg/m2) aged 20–50 years in Tabriz and Tehran, Iran. Dietary intake was assessed by a validated semi-quantitative Food Frequency Questionnaire (FFQ), including 168 food items; then, DED was calculated. MetS was defined based on the guidelines of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). Enzymatic methods were used to assess serum lipids, glucose, and insulin concentrations. Blood pressure was measured by sphygmomanometer and body composition by bioelectrical impedance analysis (BIA). Results: Participants in the higher tertiles of DED had more intake of carbohydrate, dietary fat, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and meat, fish, poultry (MFP). Increasing the DED in both methods had no association with systolic blood pressure (SBP), fasting blood sugar (FBS), low-density lipoprotein cholesterol (LDL-C), insulin, triglyceride (TG), and homeostatic model assessment of insulin resistance (HOMA-IR) even after adjustment for confounders. However, diastolic blood pressure (DBP) decreased in second tertile of DED I (β = 0.921, P = 0.004). The quantitative insulin-sensitivity check index (QUICKI) in second tertile of both DED methods had significant positive association with DED. In the second tertile of DED II, while total cholesterol (TC) significantly decreased (P crude = 0.036, P adjusted = 0.024), high-density lipoprotein cholesterol (HDL-C) increased (β = 1.096, p = 0.03). There was no significant changes in biochemical parameters in third tertile of DED I and II even after adjustment for covariates. Also, higher tertiles of DED was associated with reduced prevalence of MetS. Conclusion: High DED was associated with lower levels of blood pressure and TC but elevated levels of HDL and QUICKI independent of such confounders as age, BMI, sex, and physical activity. Further longitudinal studies are warranted to better elucidate casual associations. [ABSTRACT FROM AUTHOR]

Background: Features of metabolic syndrome such as abdominal obesity, insulin resistance, hypertension and dyslipidemia are commonly encountered in polycystic ovary syndrome (PCOS). Recent evidence has suggested an association between high serum uric acid/creatinine (UA/Cr) ratio and metabolic syndrome however, no studies have investigated this association in PCOS. The current study was conducted to investigate the relationship between UA/Cr ratio and PCOS and to identify whether UA/Cr ratio and free androgen index (FAI) have an additive interaction for detection of PCOS risk in obese women. Methods: This study enrolled 40 obese women with PCOS and 40 control women with regular menstrual cycles matched for age and body mass index (BMI). Anthropometric measurements, fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipids profile, luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), total testosterone, free androgen index (FAI), UA/Cr ratio were assessed. Results: Serum UA/Cr ratio was significantly higher in obese women with PCOS than in non-PCOS women. UA/Cr ratio was correlated with BMI, waist and neck circumferences, blood pressure, fasting insulin, HOMA-IR, lipids, LH/FSH, estradiol, DHEAS, total testosterone, FAI and SHBG. UA/Cr ratio and FAI were independent risk factors for PCOS in obese women however, the addictive interaction between UA/Cr ratio and FAI had a higher fold risk (OR: 4.3, 95% CI, 3.4–7.58) and a more significance (P = 0.002) for determination of PCOS. Conclusion: Serum UA/Cr ratio combined with FAI can exert an additive or synergistic impact on prediction of PCOS in obese women. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to evaluate the performance of Chinese visceral adiposity index (CVAI), visceral adiposity index (VAI), lipid accumulation product (LAP), triglyceride glucose (TyG) as indices in screening abnormal glucose tolerance (AGT) in Chinese women with polycystic ovary syndrome (PCOS), using the oral glucose tolerance test (OGTT) as a reference test. In addition, we essentially compared the abilities of these indices with body mass index (BMI), waist circumference (WC), fasting plasma glucose (FPG). Materials and methods: All 1113 PCOS patients evaluated in this study underwent OGTTs. The 2-h post-oral glucose load (2 h-PG) level was used to categorize subjects into two groups: those having AGT or normal glucose tolerance (NGT) levels. Results: A statistically significant positive correlation between levels of 2 h-PG and FPG, BMI, WC, LAP, VAI, CVAI, TyG, (P < 0.05), was observed. The strongest correlation was found between the levels of 2 h-PG and CVAI (r = 0.47). The CVAI provided the highest area under the receiver-operating characteristic curve (AUC) for AGT, followed by LAP, BMI, TyG, VAI, WC, and FPG. The CVAI of 32.61 (with AUC: 0.76, sensitivity: 73%, specificity: 70%, positive preductive value (PPV): 0.41, negative predictive value (NPV): 0.90) was found to be the cut-off point for AGT in Chinese women with PCOS. Conclusions: CVAI may not reliably detect AGT in Chinese women with PCOS. However, it is suitable as a first screening indicator to guide physicians to ordering OGTT. [ABSTRACT FROM AUTHOR]

Using proteomic techniques the impact of the sodium-glucose transport protein 2 inhibitor empagliflozin on cardiac protein expression in a mouse model was assessed under normal and high-fat diet (HFD) conditions. We examined the effect of obesity on serological markers and heart function in obese mice treated with or without empagliflozin and used proteomic techniques to investigate alterations in cardiac protein expression. Using bioinformatic techniques, data were screened for differentially expressed proteins (DEPs) implicated in the putative mechanism of empagliflozin's cardioprotective effects. In C57BL/6 mice, HFD increased body weight, blood lipid, and glucose levels and was associated with structural damage to the heart. Empagliflozin reduces body weight, improves glucose and lipid metabolism, alleviates obesity-induced cardiac ventricular wall thickening, and lowers cardiac tissue collagen. The expression of several proteins was altered in the heart, mainly related to lipid metabolism. Following empagliflozin treatment, the expression of several lipid metabolism-related proteins was considerably reduced. Further examination of DEPs revealed that following empagliflozin treatment, the expressions of Apoe, Apoc1, Saa2, Apoa2, and Pon1 altered dramatically, suggesting that these proteins may be the main proteins that empagliflozin uses to treat obesity-induced aberrant lipid metabolism. Empagliflozin may protect the heart by altering the expression of genes including Apoe, Apoc1, Saa2, Apoa2, and Pon1, which are all involved in lipid metabolism disturbance in obesity. [ABSTRACT FROM AUTHOR]

Background: While short-term effects of weight loss on quality of life and metabolic aspects appear to be different in metabolically healthy (MHO) and metabolically unhealthy obese (MUO), respective long-term data is still missing. Given the high relevance of long-term changes, we aimed to address these in this post-hoc analysis of the MAINTAIN trial. Methods: We analyzed 143 overweight/obese subjects (BMI ≥ 27 kg/m2, age ≥ 18 years) before and after a 3-month weight loss program (≥ 8% weight loss), after a 12-month period of a randomized weight maintenance intervention (n = 121), and after another 6 months without intervention (n = 112). Subjects were retrospectively grouped into MHO and MUO by the presence of metabolic syndrome and secondarily by estimates of insulin sensitivity (HOMA-IR and ISIClamp). Quality of life (QoL), blood pressure, lipids, HOMA-IR, and ISIClamp were assessed and evaluated using mixed model analyses. Results: Despite similar short- and long-term weight loss, weight loss-induced improvement of HOMA-IR was more pronounced in MUO than MHO after 3 months (MHO: 2.4[95%-CI: 1.9–2.9] vs. 1.6[1.1–2.1], p = 0.004; MUO: 3.6[3.2–4.0] vs. 2.0[1.6–2.4], p < 0.001; p = 0.03 for inter-group comparison). After 21 months, the beneficial effect was no longer seen in MHO (2.0[1.5–2.6], p = 1.0), while it remained partially preserved in MUO (2.9[2.4–3.3], p = 0.002). QueryShort-term improvements of lipid parameters were similar in both groups. However, long-term improvements of HDL-cholesterol and triglycerides were only seen in MUO (44.4[41.5–47.4] vs. 49.3[46.2, 52.3] mg/dl, p < 0.001; 176.8[158.9–194.8] vs. 138.8[119.4–158.3] mg/dl, p < 0.001, respectively) but not in MHO. Weight loss-induced improvements in the QoL and particularly the physical health status were maintained in MUO until the end of the trial, while benefits disappeared over time in MHO. Group allocation by HOMA-IR and ISIClamp revealed higher benefits for MUO mainly in parameters of the glucose metabolism and QoL. Conclusions: Our data demonstrates stronger and longer-lasting improvements of metabolism and QoL in MUO after weight loss. Trial registration (ClinicalTrials.gov): NCT00850629. Registered 25 February 2009, https://clinicaltrials.gov/ct2/show/NCT00850629. [ABSTRACT FROM AUTHOR]

Background: The combined roles of lifestyle factors in the risk of type 2 diabetes (T2D) are not fully investigated. In the present study, we aimed to assess the relationship between a healthy lifestyle score (HLS) and the risk of T2D in Tehranian adults. Methods: A total of 3859 individuals without T2D were recruited from participants of the Tehran Lipid and Glucose Study (2009–2011) who were followed up for a mean period of 6 years. A food frequency questionnaire was used to collect individuals' dietary intakes at baseline. HLS scores was calculated based on three pre-defined methods with focusing on 4 lifestyle factors including, no current smoking, no obesity, high physical activity, and greater adherence to the healthy diet[determined using the alternate healthy eating index-2010(AHEI-2010), modified French Programme National Nutrition Santé-Guideline Score(mPNNS-GS), and healthy diet pattern score(HDP)]. Results: Mean ± SD age of participants(44.4% men) was 41.1 ± 12.3 years. After 6-year follow-up of study, 295(7.6%) new cases of T2D were reported. Based on the age and sex-adjusted model, an inverse association was observed between the higher score of HLS-AHEI-2010 (OR = 0.24;95%CI:0.10–0.60), HLS-mPNNS-GS (OR = 0.28;95%CI:0.15–0.50), and HLS-HDP (OR = 0.39;95%CI:0.24–0.64) and the risk of T2D (P for trend < 0.05). Also, the fully-adjusted model showed that after controlling the effects of various confounders, this invers association between the higher score of HLS-AHEI-2010 (OR = 0.25;95%CI:0.10–0.61, P for trend:0.001), HLS-mPNNS-GS (OR = 0.29;95%CI:0.15–0.55,P for trend:0.001), and HLS-HDP (OR = 0.36;95%CI:0.22–0.61,P for trend < 0.001) and risk of T2D was remained significant. Conclusion: The results of this study suggested that higher score of HLS, characterized by no smoking, normal body weight, vigorous physical activity, and healthy diet, is related to decreased risk of T2D incidence. [ABSTRACT FROM AUTHOR]

Background: Postprandial glucose, insulin, and triglyceride metabolism is impaired by prolonged sitting, but enhanced by exercise. The aim of this study was to assess the effects of a continuous exercise bout with and without intermittent active interruptions to prolonged sitting on postprandial glucose, insulin, and triglycerides. Methods: Sedentary adults who were overweight to obese (n = 67; mean age 67 yr SD ± 7; BMI 31.2 kg∙m− 2 SD ± 4.1), completed three conditions: SIT: uninterrupted sitting (8-h, control); EX+SIT: sitting (1-h), moderate-intensity walking (30-min), uninterrupted sitting (6.5-h); EX+BR: sitting (1-h), moderate-intensity walking (30- min), sitting interrupted every 30-min with 3-min of light-intensity walking (6.5 h). Participants consumed standardized breakfast and lunch meals and blood was sampled at 13 time-points. Results: When compared to SIT, EX+SIT increased total area under the curve (tAUC) for glucose by 2% [0.1–4.1%] and EX+BR by 3% [0.6–4.7%] (all p < 0.05). Compared to SIT, EX+SIT reduced insulin and insulin:glucose ratio tAUC by 18% [11–22%] and 21% [8–33%], respectively; and EX+BR reduced values by 25% [19–31%] and 28% [15–38%], respectively (all p < 0.001 vs SIT, all p < 0.05 EX+SIT-vs-EX+BR). Compared to SIT, EX+BR reduced triglyceride tAUC by 6% [1–10%] (p = 0.01 vs SIT), and compared to EX+SIT, EX+BR reduced this value by 5% [0.1–8.8%] (p = 0.047 vs EX+SIT). The magnitude of reduction in insulin tAUC from SIT-to-EX+BR was greater in those with increased basal insulin resistance. No reduction in triglyceride tAUC from SIT-to-EX+BR was apparent in those with high fasting triglycerides. Conclusions: Additional reductions in postprandial insulin-glucose dynamics and triglycerides may be achieved by combining exercise with breaks in sitting. Relative to uninterrupted sitting, this strategy may reduce postprandial insulin more in those with high basal insulin resistance, but those with high fasting triglycerides may be resistant to such intervention-induced reductions in triglycerides. Trial registration: Australia New Zealand Clinical Trials Registry (ACTRN12614000737639). [ABSTRACT FROM AUTHOR]

Background: Dietary fatty acids are important dietary determinants of metabolic disorders in human. However, it is important to develop an index that considers not only the amount of dietary fatty acids but also the structure, fluidity and melting point of them. In the current study we investigated the association between a novel dietary lipophilic index (LI) with metabolic profile and dyslipidemia in a community based study in Tabriz-Iran. Methods: Dietary data were collected using a validated, 79-food item, semi-quantitative food frequency questionnaire, and dietary LI was calculated. Anthropometric variables were measured and metabolic profile including blood sugar, serum lipids and liver enzymes were assessed. Metabolic syndrome was defined according to the adult treatment panel (ATP) III criteria. Results: The mean age of the participants was 42.53 ± 12.03 years and most of the participants were women. Mean of dietary LI was 34.99 ± 6.91. Higher dietary LI was associated with higher body mass index (BMI) (β = 0.17, P < 0.04), waist circumference (β = 0.18, P < 0.01) and systolic blood pressure (β = 0.27, P < 0.01). Also LI was increased with increasing waist circumference (0.001), low density lipoprotein cholesterol (LDL-C) (0.001), and negatively associated with high density lipoprotein cholesterol (HDL-C) (0.001). Conclusion: The novel dietary LI was considered as a useful tool in prediction of cardio-metabolic risk factors including general and central obesity, dyslipidemia and metabolic syndrome in a population-based study in Iran. Further researches in other disease and populations could highlight the application of this index in clinical settings. [ABSTRACT FROM AUTHOR]

Background: The escalating prevalence of adrenal incidentaloma (AI) has been associated with the improvement of radiologic techniques and widespread imaging in aging population. It is currently unclear whether patients with obesity more likely develop AI and the current rise in the prevalence of AI could be at least partly associated with the respective rise in obesity. We compared the prevalence and characteristics of non-functional (NF) and autonomous cortisol secreting (ACS) adrenal incidentalomas (AIs) after the study population was stratified by different body mass indexes (BMI) and age groups. Methods: Retrospective cross-sectional study comprising of 432 patients (40.6% male, 59.4% female) with NFAI (N = 290) and ACS (N = 142), of median age 63.4 (54.0–71.6) years and median BMI 28.6 (25.5–31.7) kg/m2. The data collection contained 11.132 points including demographic, anthropometric, radiologic, hormonal and metabolic parameters. Results: We observed 68–87% higher prevalence of AI across different age groups in NFAI and ACS in obese/overweight compared to normal weight subjects. Patients with ACS were older (P = 0.008), with higher basal cortisol (P < 0.001), lower basal DHEAS (P = 0.001), lower suppression DHEAS (P = 0.027) and higher aldosterone (P = 0.039). AIs with ACS were larger than NFAI (P < 0.001). Interestingly, ACS group had lower body mass (P = 0.023) and did not differ in BMI, blood pressure, heart rate, lipid profile, fasting glucose and presence of diabetes mellitus type 2 when compared to NFAI., By contrast to the similarity of metabolic profiles in ACS and NFAI, some components of adverse metabolic traits were rather associated with higher BMI and older age, in particular in NFAI. Conclusion: The prevalence of NFAI and ACS were significantly higher in overweight/obese subgroup across the age distribution. Stratification by age and BMI displayed significant differences in some metabolic traits, in particular in NFAI. [ABSTRACT FROM AUTHOR]

Background: To determine if overweight/obese pregnant women have altered microRNA expression patterns in fetal umbilical cord blood that may affect the development of offspring. Methods: Umbilical cord blood samples were obtained from the fetuses of 34 overweight/obese and 32 normal-weight women after delivery. Next generation sequencing (NGS) analyzed their miRNA expression patterns. miRanda and TargetScan databases were used to predict the miRNAs' target genes followed by analyses of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to perform function grouping and pathway analyses. qRT-PCR verified the identity of differentially expressed miRNAs that were revealed in the NGS results. Results: There was a positive correlation between newborn body weight and pregestational BMI of pregnant individuals (r = 0.48, P < 0.001). One hundred and eight miRNAs were differentially expressed between the normal and overweight/obese groups, which target genes were enriched in the metabolic pathway. Five C19MC miRNAs (miR-516a-5p, miR-516b-5p, miR-520a-3p, miR-1323, miR-523-5p) were upregulated in the overweight/obese group. Target enrichment analysis suggests their involvement in post-embryonic development, lipid and glucose homeostasis, T cell differentiation and nervous system development. Conclusions: C19MC miRNA expression upregulation in the fetal circulation during the gestation of overweight/obese pregnant women may contribute to altered multisystem metabolic pathway development in their offspring. [ABSTRACT FROM AUTHOR]

Background: Diet and exercise play important roles in ameliorating metabolic syndrome. Yunkang 10 (Camellia sinensis var. assamica) is a most cultivated tea variety for making tea in the Southwestern China. Currently, there is no report of healthy effects of Yunkang 10 green tea (YKGT) and treadmill exercise (Ex) on high fat diet induced metabolic syndrome (MetS). We aimed to investigate the beneficial effects and molecular mechanism of YKGT and Ex using high fat diet induced MetS of C57BL/6 mice. Methods: Catechins and caffeine in water extract of YKGT were measured via high performance liquid chromatography (HPLC). 10-week old mice were fed with high fat diet (HFD) for 10 weeks to induce obese mice. Then the obese mice were fed with continuous high fat diet (HFD), HFD with YKGT, HFD with Ex, and HFD with both YKGT and Ex for 8 weeks, respectively. The another group of 10-week old mice fed with low fat diet (LFD) were used as control. Results: HPLC data revealed that YKGT has abundantly high concentration of epigallocatechin gallate (EGCG) and caffeine compared to Longjing 43 (Camellia sinensis var. sinensis) green tea. YKGT and Ex significantly decreased the level of blood glucose, serum total cholesterol (TC), triglyceride (TG), insulin, and alanine aminotransferase activity (ALT) when compared to HFD group. The fatty liver and hepatic pro-inflammatory gene expression in the YKGT, Ex and YKGT+Ex groups was mitigated significantly compared with HFD group, respectively. The phosphorylation of inhibitor of nuclear factor kappa-B kinase α/β (IKKα/β) and inhibitor of nuclear factor kappa-B α (IkBα) protein in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway was also decreased in YKGT or YKGT+Ex groups. The combination of YKGT and Ex prevented gene expression for lipid synthesis in the liver tissue, and significantly upregulated mRNA level of glucose transport genes in the skeletal muscles, when compared to the HFD group. Conclusions: This study demonstrated that YKGT supplement or exercise appeared to reverse preexisting metabolic syndrome, and effectively relieved the fatty liver and hepatic inflammatory response induced by high fat diet. YKGT supplement and treadmill exercise together had better beneficial effects than only one intervention. [ABSTRACT FROM AUTHOR]

Background: Hypovitaminosis D is associated with many features of the metabolic syndrome, including non-alcoholic fatty liver disease. Vitamin D-enriched mushrooms extracts exert a synergistic anti-inflammatory effect. The aim of the present study is to determine the immunomodulatory effect of oral administration of vitamin D-enriched mushrooms extracts on high-fat diet (HFD) animal model of non-alcoholic steatohepatitis (NASH).Methods: C57BL/6 mice on HFD were orally administered with vitamin D supplement, Lentinula edodes (LE) mushrooms extract, or vitamin D-enriched mushrooms extract for 25 weeks. Mice were studied for the effect of the treatment on the immune system, liver functions and histology, insulin resistance and lipid profile.Results: Treatment with vitamin D-enriched LE extracts was associated with significant attenuation of the rate of total body fat accumulation, along with a decrease in hepatic fat content as measured by an EchoMRI. Significant alleviation of liver damage manifested by a marked decrease in ALT, and AST serum levels (from 900 and 1021 U/L in the control group to 313 and 340; 294 and 292; and 366 and 321 U/L for ALT and AST, in Vit D, LE and LE + Vit D treated groups, respectively). A corresponding effect on hepatocyte ballooning were also noted. A significant decrease in serum triglycerides (from 103 to 75, 69 and 72 mg/dL), total cholesterol (from 267 to 160, 157 and 184 mg/dL), and LDL cholesterol (from 193 mg/dL to 133, 115 and 124 mg/dL) along with an increase in the HDL/LDL ratio, and improved glucose levels were documented. These beneficial effects were associated with a systemic immunomodulatory effect associated with an increased CD4/CD8 lymphocyte ratio (from 1.38 in the control group to 1.69, 1.71 and 1.63), and a pro- to an anti-inflammatory cytokine shift.Conclusions: Oral administration of vitamin-D enriched mushrooms extracts exerts an immune modulatory hepato-protective effect in NASH model. [ABSTRACT FROM AUTHOR]

Background: Black pepper or Piper nigrum is a well-known spice, rich in a variety of bioactive compounds, and widely used in many cuisines across the world. In the Indian traditional systems of medicine, it is used to treat gastric and respiratory ailments. The purpose of this investigation is to study the antihyperlipidemic and antiobesity effects of piperonal in high-fat diet (HFD)-induced obese rats. Methods: Piperonal, an active constituent of Piper nigrum seeds, was isolated and confirmed by HPLC, 1H and 13C NMR spectroscopy. Male SD rats were fed on HFD for 22 weeks; Piperonal was supplemented from the 16th week as mentioned in the experimental design. Changes in body weight and body composition were measured by TOBEC, bone mineral composition and density were measured by DXA, and adipose tissue distribution was measured by 7 T--MRI. Plasma levels of glucose, insulin, insulin resistance and lipid profiles of plasma, liver and kidney, adipocyte hormones and liver antioxidants were evaluated using standard kit methods. Expression levels of adipogenic and lipogenic genes, such as PPAR-γ, FAS, Fab-4, UCP-2, SREBP-1c, ACC, HMG-COA and TNF-α were measured by RT-PCR. Histopathological examination of adipose and liver tissues was also carried out in experimental rats. Results: HFD substantially induced body weight, fat%, adipocyte size, circulatory and tissue lipid profiles. It elevated the plasma levels of insulin, insulin resistance and leptin but decreased the levels of adiponectin, BMC and BMD. Increased expression of PPAR-γ, FAS, Fab-4, UCP-2, SREBP-1c, ACC, and TNF-α was noticed in HFD-fed rats. However, supplementation of piperonal (20, 30 and 40 mg/kg b.wt) for 42 days considerably and dose-dependently attenuated the HFD-induced alterations, with the maximum therapeutic activity being noticed at 40 mg/kg b.wt. Conclusions: Piperonal significantly attenuated HFD-induced body weight and biochemical changes through modulation of key lipid metabolizing and obesogenic genes. Our findings demonstrate the efficacy of piperonal as a potent antiobesity agent, provide scientific evidence for its traditional use and suggest the possible mechanism of action. [ABSTRACT FROM AUTHOR]

Background: The relationship between dietary components and nonalcoholic fatty liver disease (NAFLD) needs to be further investigated. The potential health benefits of cardamom have been found in some studies. Cardamom showed beneficial effect on hepatomegaly, dyslipidemia, and fasting hyperglycemia in animals. However, some adverse effects of cardamom have been reported in animals. No previous human study had been conducted on the effects of cardamom in NAFLD. This study aims to determine the effects of green cardamom (Elettaria cardamomum) supplementation on blood glucose indices, lipids, inflammatory profiles, and liver function, especially by examining irisin, paraxonase-1 (PON1) and sirtuin-1 (Sirt1) in obese patients with NAFLD.Methods: This trial is to be conducted at the polyclinic of the National Iranian Oil Company (NIOC) Central Hospital, Tehran. Eighty obese patients with NAFLD will be selected according to the eligibility criteria. The NAFLD diagnosis method is ultrasonography. Patients will be randomly divided into two groups by a random-number table (cardamom and placebo groups, two 500-mg capsules, three times/day, taken with meals for 3 months, follow-up monthly). General characteristics, dietary intakes (at the beginning, middle, and end), and physical activity (at the beginning and end) will be assessed using a general, 24-h food recall, and short-form International Physical Activity Questionnaires (IPAQ), respectively. Lifestyle advice will be presented to both groups identically. At the beginning and the end, anthropometrics (weight, height, and waist circumference), blood pressure, extent of fatty liver, and blood biomarkers, including serum glucose indices (fasting blood sugar (FBS)) and insulin (FBI), homeostasis model assessment-insulin resistance (HOMA-IR), Quantitative Insulin Sensitivity Check Index (QUICKI)), lipids (triglyceride (TG), low-density lipoprotein-cholesterol (LDL-c), high-density lipoprotein-cholesterol (HDL-c), total cholesterol (TC)), inflammatory markers (highly sensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)), liver enzymes (alanine transaminase (ALT), aspartate transaminase (AST)), irisin, PON1, and Sirt1, will be determined.Discussion: This trial would be the first to assess the effects of green cardamom on several blood factors, including glucose indices, lipids, inflammatory markers, liver enzymes, irisin, PON1, and Sirt1, and blood pressure and anthropometry in obese patients with NAFLD. Further study of cardamom's potential in improving NAFLD is suggested.Trial Registration: Iranian Registry of Clinical Trials (IRCT), ID number: IRCT2015121317254N4 . Registered on 27 December 2015. [ABSTRACT FROM AUTHOR]

Background: Obesity is currently regarded as a pro-inflammatory condition during which leptin (Ob gene product) might act as a risk factor for Cardiovascular Diseases (CVD) including Acute Myocardial Infarction (AMI). There is a marked increase in circulating leptin concentrations and inflammatory markers such as Tumor Necrosis Factor-α (TNF-α) in AMI patients but still the association of leptin with inflammation during AMI is not known. The present study suggest that elevated levels of leptin might elicit the risk for CVD by signaling for the secretion of inflammatory cytokines especially, TNF-α. Methods: Blood samples were collected from 100 CVD subjects diagnosed for AMI immediately after their admission to the hospital and serum leptin, insulin, glucose, lipids and inflammatory marker such as TNF-α were measured. 5 ml random (non-fasting) blood was collected from 100 non-CVD (control) subjects and the results obtained in case of AMI subjects were compared with that of the control subjects. The subjects under study included both men and women belonging to the age group of 35 - 75 and they were classified based on their BMI as normal weight, overweight and obese. Results: Circulating levels of leptin are found to be elevated in obese control subjects and in patients with AMI irrespective of their Body Mass Index (BMI). In addition, leptin is also found to be positively correlated to serum triglycerides, insulin and TNF-α in AMI subjects. MANOVA analysis suggests that leptin might influence the synthesis of insulin and TNF-α. This is the first report relating leptin to TNF-α in Chennai based population, India. Conclusions: Hyperleptinemia might act as a risk marker for AMI. The present study suggests that at elevated levels, leptin may favor atherosclerosis by promoting the synthesis of TNF-α and insulin. However, our report warrants further investigation both in vitro and in vivo to determine the exact mechanism behind the pro-atherogenic role of leptin. The observed positive correlation between leptin and BMI in both AMI and control subjects suggests that obese subjects manifest leptin resistance and hence, they possess a greater risk for the incidence of CVD. [ABSTRACT FROM AUTHOR]

Background: Glucagon-like Peptide-1 (GLP-1) is an incretin hormone secreted from the gastrointestinal tract that facilitates the glucose-dependent insulin response. Additionally, GLP-1 is thought to be involved in energy homeostasis. Currently little is known about GLP-1's responsiveness to an energy surplus, a fundamental cause of obesity and diabetes. Our objective was to examine the response of serum GLP-1 to short-term (7 day) overfeeding in young men. Methods: Seventy-two young men from the Canadian province of Newfoundland were recruited for the study. For 7-days, the subjects consumed 70% more calories than required at baseline. Various measurements including: anthropometrics, body composition, markers of glucose/lipid metabolism and serum total GLP-1, were taken at a fasted state before (day 1) and after (day 8) the challenge. Paired t-test analyses were used to assess the change in variables after the overfeeding period. Additionally, the relationship between serum GLP-1 and the measured variables at baseline and change due to overfeeding were analyzed. Results: Serum GLP-1 was significantly increased in all groups in response to the 7-day energy surplus, indicating the increase was independent of adiposity status. There was no significant difference in fasting GLP-1 at baseline between the normal weight and overweight/obese groups. At baseline, GLP-1 concentration negatively correlated with HDL-cholesterol and positively correlated with triacylglycerols and markers of insulin resistance in the overweight/obese group. Also GLP-1 was negatively correlated with change in percent gynoid fat in the overweight/obese subjects. Percent change in GLP-1 was negatively associated with percent change in gynoid fat in the normal weight group and positively associated with percent change in cholesterol in the overweight/obese group. Percentage change of circulating triacylglycerols was positively associated with percent change in GLP-1 in both adiposity groups. Conclusion: Our findings showed that GLP-1 serum concentration is not a significant factor in determining obesity status. The increase of GLP-1 in all subjects regardless of obesity status, suggest GLP-1 serves as a protective role, counteracting energy surplus. [ABSTRACT FROM AUTHOR]

Background: The prevalence of obesity among Mexican women is high and it could be related to micronutrient status. We evaluated in a cross-sectional study the associations of zinc and vitamins A, C and E concentrations with BMI, central adiposity, body fat and leptin concentration. Methods: Women aged 37 ± 7.5 years (n = 580) from 6 rural communities in Mexico were evaluated. Anthropometric measurements included weight, height, waist and hip circumference. A fasting blood sample was taken for the analysis of glucose, lipid profile, leptin, zinc, and vitamins A, C and E. Body composition was determined by DEXA (Hologic Mod Explorer). Results: The prevalence of overweight and obesity was 36% (BMI>25 Kg/m2) and 44% (BMI>30 Kg/m2), respectively. Prevalence of zinc and vitamins C and E deficiencies were similar in obese, overweight and normal weight women. No vitamin A deficiency was found. Vitamin C was negatively associated with BMI, waist-to-height ratio, and leptin concentrations (p<0.05). Vitamin A was positively associated with leptin (p<0.05). When stratifying by BMI, % body fat and waist circumference, high leptin concentrations were associated with lower zinc and lower vitamin C concentrations in women with obesity (p<0.05) and higher vitamin A concentrations in women without obesity (p<0.01). Vitamin E status was not associated with any markers of obesity. Conclusion: Zinc and vitamins A and C are associated with obesity, adiposity and leptin concentration in women from rural Mexico, and may play an important role in fat deposition. The causality of these associations needs to be confirmed. [ABSTRACT FROM AUTHOR]

Background: Individuals with normal weight obesity (NWO) are predisposed to having cardiometabolic disorders. This study aims to investigate the circulating levels of vaspin, leptin and their association with glycemic and lipid profiles in women with NWO. Methods: Forty women with body mass index (BMI) = 18.5–24.9 kg/m2 and fat mass (FM) ≥ 30% were assigned in the NWO group. Thirty age-matched women with identical BMI range, and FM < 30% (normal weight non-obese; NWNO) were considered as a control group. In addition to anthropometric measurements, glycemic and lipid profiles and circulating levels of leptin and vaspin were measured. Results: The mean ± standard deviation (SD) age of participants was 28.76 ± 4.76 years in the NWO group and 29.23 ± 4.50 years in the control group. The NWO group had the higher mean serum levels of insulin (9.02 ± 4.75 vs. 6.24 ± 2.51, P = 0.009), leptin (17.31 ± 8.10 vs. 9.94 ± 4.30, P < 0.001) and homeostatic model assessment of insulin resistance (HOMA-IR) (33.77 ± 20.71 vs. 23.48 ± 10.03, P = 0.009) compared to the NWNO group. The serum level of vaspin was higher in the NWO group compared to the control group (34.82 pg/ml vs. 27.72 pg/ml, respectively, P = 0.12). In NWO group, the serum levels of leptin had positive correlation with FBS (r = 0.45, P = 0.02), insulin (r = 0.51, P = 0.008), and HOMA-IR (r = 0.46, P = 0.02) and vaspin concentration was associated with insulin (r = 0.36, P = 0.02) and HOMA-IR (r = 0.30, P = 0.06), positively. Conclusion: It is concluded that the concentration of insulin and HOMA-IR index were significantly higher in women with NWO compared to NWNO. Higher concentrations of leptin and vaspin in the NWO group were associated with glycemic profile. [ABSTRACT FROM AUTHOR]

Background: Some polyphenols are known to improve the symptoms of diabetes. In the present study, we investigated the effects of a polyphenol-rich extract of maple syrup (MSx) on a diabetic mouse model. Methods: KK-Ay mice were fed a normal or 0.05% MSx-supplemented diet for 42 days. Body weight, food intake, serum biochemical parameters, and fecal total bile acid were measured. Gene expression of liver and epididymal white adipose tissue (WAT) and cecal microbiota were analyzed. Data were analyzed with an unpaired two-tailed Student's t test or Welch's t test according to the results of the F test. Results: Serum low-density lipoprotein cholesterol levels were significantly reduced in mice that consumed MSx. Hepatic genes related to fatty acid degradation and cholesterol catabolism were upregulated in mice that consumed MSx. In contrast, the expression of genes related to lipid metabolism in WAT was unaffected by the intake of MSx. There were no significant differences between the two groups in terms of total bile acid level in the feces and the relative abundance of bacteria in the cecum. Conclusion: Our results primarily indicate that MSx can help alleviate one of the symptoms of dyslipidemia. [ABSTRACT FROM AUTHOR]

Background: To investigate the prevalence of cardiovascular disease (CVD) risk factors and assess the 10-year risk of CVD in non-menopausal and postmenopausal women with type 2 diabetes mellitus (T2DM). Methods: A total of 569 patients with T2DM at a Chinese tertiary hospital were investigated using the Framingham Risk Score (FRS). We evaluated the 10-year risk of CVD, clinical and menopause characteristics in all subjects. Results: Among the 569 diabetic patients, the incidence of smoking, dyslipidemia, hypertension, overweight or obesity, and nonalcoholic fatty liver disease (NAFLD) was 0.7, 36.2, 38.1 56.6 and 58.2%, respectively. The usage rate of hypoglycemic agents, antihypertensive agents, lipid modulators and antithrombotic drugs was 88.6, 78.3, 50.0 and 27.1%, respectively. However, only 1.2% of inpatients achieved the three target goals for the control of blood glucose (HbA1c < 7%), blood pressure (systolic blood pressure < 130 mmHg, diastolic blood pressure < 80 mmHg), and blood lipids (total cholesterol < 174 mg/dL). The 10-year risk of CVD was (1.6 ± 1.5%) and tended to increase along with age (F = 27.726, P < 0.001). For all subjects (n = 569), multiple linear regression analysis showed that menopause (β = 0.275, P < 0.001), low-density lipoprotein cholesterol (LDL-C) (β = 0.212, P < 0.001), fasting plasma glucose (FPG) (β = 0.093, P = 0.018) and waist-to-hip-ratio (β = − 0.078, P = 0.047) were risk factors of 10-year risk of CVD, which may explain the variance of 14.3%. In the postmenopausal group (n = 397), LDL-C (β = 0.227, P < 0.001), FPG (β = 0.139, P = 0.003) and time since menopause (β = 0.230, P < 0.001) were found to be associated with CVD, which may explain the variance of 14.6%. Conclusion: The incidence of dyslipidmia, hypertension, overweight or obesity and NAFLD is high. The level of control of blood glucose, blood pressure, and blood lipids was found to be extremely low and the treatment status was not ideal. Besides menopause, LDL-C, FPG and time since menopause were found to be independent risk factors for the 10-year risk of CVD. Therefore, it is necessary to focus on comprehensive control of multiple risk factors, such as plasma glucose, blood pressure and serum lipid. [ABSTRACT FROM AUTHOR]

Objectives: The present study was conducted on healthy obese persons to determine: (i) the association between total cholesterol, triglycerides, HDL cholesterol, total cholesterol/HDL ratio and fasting blood glucose (FBG) with (a) BMI, (b) waist circumference (WC) and (c) body fat and (ii) the presence of undiagnosed type 2 diabetes (based on fasting blood glucose) in the participants. There were 1140 participants of both sexes (female:male 697:443; group mean age 44.0 ± 10.8 years; BMI ≥ 25 kg/m2) from four regions of India. The participants were assessed for (i) BMI and WC, (ii) body fat, (iii) fasting serum lipid profile and (iv) FBG. Statistical significance (α) was set at 0.05. Results: Based on a linear regression analysis triglycerides acted as a significant predictor for body fat. Triglycerides showed a significant negative correlation with BMI and body fat. HDL cholesterol was significantly negatively correlated with waist circumference and positively correlated with body fat. Total cholesterol/HDL ratio was positively correlated with waist circumference and negatively correlated with body fat. A significant positive correlation of FBG and waist circumference was also observed. Among the healthy participants 34.2% had pre-diabetes and 13.6% had diabetes. [ABSTRACT FROM AUTHOR]

The article discusses a cross sectional study which examines the prevalence and risk factors of metabolic syndrome among the adult population in Saudi Arabia. The study used anthropometric measurements, statistics and laboratory data to evaluate subjects with metabolic syndrome. Results show that Saudi adult population has obtained a high prevalence of metabolic problem and needs an urgent execution of health care strategies to control borth mortality and morbidity.