Blood Total Cholesterol Levels Research Articles

Cyclocarya paliurus triterpenoids suppress hepatic gluconeogenesis via AMPK-mediated cAMP/PKA/CREB pathway

BackgroundAbnormal enhancement of hepatic gluconeogenesis is a vital mechanism of the pathogenesis of Type 2 diabetes mellitus (T2DM); thus, its suppression may present an efficient therapeutic strategy for T2DM. Cyclocarya paliurus (CP), a plant species native to China, has been reported to have anti-hyperglycemia activity. Our previous studies have revealed that Cyclocarya paliurus triterpenic acids (CPT) exert the favorable glucose-lowering activity, but the regulatory effect of CPT on hepatic gluconeogenesis is still unclarified. PurposeThis study aimed to investigate the potential role and mechanism of CPT in gluconeogenesis. Study designIn this study, the ameliorative effect and underlying mechanism of CPT on gluconeogenesis were investigated: high-fat diet and streptozotocin-induced T2DM mice and glucagon-challenged mouse primary hepatocytes. MethodsT2DM model mice with or without oral administration of CPT for 4 weeks were monitored for body weight, glucose and lipid metabolism. Hematoxylin and eosin staining was used to observe liver lipid deposition. Real-time PCR assays were performed to examine the mRNA expression of glucose-6-phosphate (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK), two key enzymes involved in liver gluconeogenesis. Western blotting was used to determine AMP-dependent protein kinase (AMPK) expression and induction of the glucagon signaling pathway. The possible mechanism of CPT on liver gluconeogenesis was further explored in glucagon-induced mouse primary hepatocytes. ResultsIn vivo and in vitro experiments revealed that CPT treatment significantly reduced fasting blood glucose, total cholesterol and triglyceride levels, and improved insulin resistance. Furthermore, CPT could obviously decreased the mRNA and protein expression of G6Pase and PEPCK, the cyclic AMP content, the phosphorylation level of protein kinase A and cyclic AMP response element-binding protein. But CPT promoted the phosphorylation of AMP-dependent protein kinase (AMPK) and activation of phosphodiesterase 4B. Mechanistically, intervention with Compound C (an AMPK inhibitor) partially blocked the suppressive effect of CPT on hepatic gluconeogenesis. ConclusionThese findings suggested that CPT may inhibit hepatic gluconeogenesis against T2DM by activating AMPK.

Oxidative and antioxidant changes in blood of young people with premature coronary artery disease and abdominal obesity

Aim. To study the oxidative and antioxidant blood profile in young people with premature coronary artery disease (CAD) and abdominal obesity (AO).Material and methods. The study included 169 people. The main group consisted of 47 patients diagnosed with premature (<45 years of age) CAD, while 22 of them with AO and 25 without AO. The control group included 122 people without CAD, comparable with the main group in sex, age and body mass index. Among them, there are 67 people with AO and 55 people without AO. In all examined patients, the blood levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, MDA-modified oxidized high-density lipoprotein, superoxide dismutase (SOD), glutathione peroxidase 1, and whole blood total antioxidant capacity (TAC) were determined. Statistical processing was carried out in the SPSS 13.0 program.Results. The blood TAC was 2,3 times lower in persons with CAD than in those without CAD, and amounted to 1,58 mmol of trolox. The blood level of SOD in patients with CAD was 1,16 times higher than in the group of people without CAD. The relative odds of premature CAD were associated with decreased TAC (B=-2,855; Exp(B)=0,058; 95% confidence interval (CI), 0,008-0,392; p=0,004) and increased level of SOD (B=0,105; Exp(B)=1,076; 95% CI, 1,031-1,196; p=0,006), regardless of sex, age, risk factors. Conclusion. Thus, an increased SOD and reduced TAC can be potential biomarkers for premature CAD in people under 45 years of age.

Circulating microRNAs as putative mediators in the association between short-term exposure to ambient air pollution and cardiovascular biomarkers

BackgroundExposure to ambient air pollution is associated with increased cardiovascular morbidity and mortality. Circulating microRNAs (miRNAs) may mediate cardiovascular effects of exposure to air pollution. This study aims to investigate whether circulating miRNAs mediate the associations between short-term human exposure to ambient air pollution and cardiovascular biomarkers. MethodsTwenty-four healthy adults residing in the Research Triangle area of North Carolina, USA were enrolled between December 2016 and July 2019. Circulating miRNAs, protein, and lipid biomarkers were assessed repeatedly for 3 sessions separated by at least 7 days. Linear mixed-effects models were used to assess the associations between air pollutant concentrations obtained from nearby air quality monitoring stations and miRNAs controlling for covariates including omega-3 index, relative humidity, and temperature. miRNAs that were significantly altered were then matched with protein or blood lipid biomarkers using either Ingenuity Pathway Analysis or a literature search. A mediation analysis was performed to test the statistical significance of miRNA’s mediating effects between exposure to air pollution and cardiovascular biomarkers. ResultsShort-term exposure to ambient fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) was associated with changes in 11, 9, and 24 circulating miRNAs, respectively. Pathway analysis showed that several miRNAs including miR-125b-5p, miR-144–5p, miR-26a-5p, and miR-34a-5p may mediate the effects of air pollutant exposure on the changes of downstream protein / lipid biomarkers including serum amyloid A (SAA), C-reactive protein (CRP), soluble vascular adhesive molecules 1 (sICAM1), total cholesterol, and high-density lipoproteins (HDL). Mediation analysis showed that only miR-26a-5p significantly mediated air pollutant (PM2.5 and NO2)-induced effects on blood CRP and total cholesterol levels. For example, 34.1% of PM2.5–associated changes in CRP were significantly mediated by miR-26a-5p at lag4 [indirect effects, 0.06 (0.02, 0.10), P = 0.005]. Similarly, the proportions of indirect effects of miR-26a-5p on the association between NO2 exposure and CRP were 46.8% at lag2 [0.06 (0.02, 0.11), P = 0.003], 61.2% at lag3 [0.05 (0.00, 0.09), P = 0.04], and 30.8% at 5-day moving average [0.06 (0.02, 0.10), P = 0.01]. In addition, omega-3 index may be a significant modifying factor of the mediated effects of miRNAs. ConclusionsThis study demonstrates that short-term exposure to ambient PM2.5, O3, and NO2 was associated with specific circulating miRNAs, and some of which may mediate their effects on the downstream inflammation and blood lipid markers.

Scutellarin Improves Type 2 Diabetic Cardiomyopathy by Regulating Cardiomyocyte Autophagy and Apoptosis.

Diabetes cardiomyopathy has metabolic disorder and abnormality of cardiomyocytes, which is closely related to autophagy or apoptosis of cardiomyocytes. Scutellarin (SCU) is an important monomer extracted from Erigeron breviscapus (vant.) Hand.-Mazz. This study was conducted to investigate the function of SCU on apoptosis and autophagy of myocardial cells. We established a model of type 2 diabetic cardiomyopathy by high-fat and high-sugar diet. The results indicated that SCU downregulated blood glucose, total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels and upregulated high-density lipoprotein (HDL) level. In addition, SCU downregulated lactic dehydrogenase 1 (LDH1) and creatine kinase (CK) levels. Meanwhile, SCU improved the myocardium morphology and reduced myocardial apoptosis. Furthermore, SCU promoted the mRNA and protein expression of autophagy-related factors (Beclin-1 and LC3-II) and inhibited the mRNA and protein expression of apoptosis-related factors (caspase-3, caspase-8, caspase-9, caspase-12, Bax, and Cyt-C). In conclusion, SCU can promote autophagy signal pathway by upregulating the autophagy-related factors and inhibit the apoptotic signal pathway by downregulating apoptosis-related factors, thereby relieving type 2 diabetic cardiomyopathy (T2DC).

Ameliorating Effect of Morin Hydrate on Chronic Restraint Stress-induced Biochemical Disruption, Neuronal, and Behavioral Dysfunctions in BALB/c Mice.

Morin hydrate (MH) is a bioflavonoid component of many fruits and vegetables. Our previous research demonstrated that MH provides neuroprotection in mouse models of acute restraint stress and sleep deprivation by attenuating hippocampal neuronal damage and enhancing memory. Based on these findings, our study investigated the role of MH in chronic stress-induced neuronal and biochemical perturbations in BALB/c mice. Male BALB/c mice were divided into 6 groups (n=6). Groups 1 and 2 received vehicle (10 mL/kg normal saline), groups 3-5 received MH (5, 10, 20 mg/kg IP), while group 6 received ginseng (25 mg/kg) daily and 30 minutes afterward were restrained in a plastic cylindrical restrainer for 14 days. Immobility time in the forced swim test increased in the MH-treated group, indicating an antidepressant-like effect. Also, a reduction in frequency and duration of open arms exploration was observed in the elevated plus-maze (EPM) test in stressed mice, and administration of MH (5, 10, 20 mg/kg, IP) reversed these effects. An increase in blood levels of glucose, triglycerides, total cholesterol, and brain malondialdehyde and nitrite levels was observed in the stressed groups, which was reversed by MH. Furthermore, MH reversed the stress-induced reduction in HDL cholesterol and glutathione (GSH) levels and attenuated stress-induced alterations in the prefrontal cortex and hippocampus. Our findings suggest that MH attenuated chronic restraint stress-behavioral and biochemical perturbations, probably due to its capability to decrease oxidative stress and brain neuronal damage. Chronic stress perturbs physiological and psychological homeostasis;Morin hydrate normalized chronic stress-induced biochemical disruptions;Morin hydrate attenuated structural changes in prefrontal cortex and hippocampus. Stress is a state of being overwhelmed by demands exceeding the personal and social means of coping. Exposure to excessive stress has resulted in disruption of neurochemical and physiological processes, which sometimes manifest as behavioural abnormalities. Therefore to cope with the stressful life style, there is need to develop a therapeutic agent of plant origin. Morin hydrate is a flavonoid with known antioxidant and neuroprotective properties; however, its effect in a stressful condition has not been studies. The study thus evaluated ameliorating effect of Morin hydrate on chronic restraint stress-induced biochemical disruption, neuronal and behavioral dysfunctions in BALB/c mice. To achieve this, mice were exposed to chronic restraint stress protocol for fourteen days. Behavioural changes were examined using various techniques. The vital parameters like antioxidant, glucose and nitrite levels were also taken. Our findings show that Morin hydrate prevented behavioral abnormalities and damage to the brain cells. It also inhibited stress-induced biochemical disturbance.

Antihyperglycemic activity of L-norvaline and L-arginine in high-fat diet and streptozotocin-treated male rats

BackgroundA decrease in nitric oxide (NO) bioavailability has been shown to cause hyperglycemia, type II diabetes mellitus (DM), and chronic cardio-metabolic complications. In turn, hyperglycemia and hypercholesterolemia are associated with increased oxidative stress that leads to reduced nitric oxide bioavailability through disruption of L-arginine transport into cells, inactivation of nitric oxide synthase, and activation of arginase. Upregulation of arginase has been demonstrated in both diabetic patients and animal models of hyperglycemia and type 2 diabetes. L-norvaline is a nonselective inhibitor of arginase that increases NO production and promotes the normal functioning of the vascular endothelium. Another means of increasing NO bioavailability in the cardiovascular system is L-arginine supplementation. Whether L-norvaline and L-arginine have antihyperglycemic effects has not been studied. HypothesisWe hypothesized that inhibition of arginase will provide an antihyperglycemic effect and, as a result of the recovery of NO bioavailability, will protect against oxidative stress and hypercholesterolemia. MethodsRats were fed a high-fat diet (HFD) for three weeks concomitant with the two-time injection of 30 mg/kg of streptozotocin (STZ) to induce stable hyperglycemia. We studied the antihyperglycemic properties of arginase inhibition (via L-norvaline) and its combination with NOS substrate supplementation (via L-arginine). ResultsTreatment of HFD/STZ mice with L-norvaline and L-arginine reduced fasting blood glucose levels by 27.1% vs. untreated HFD/STZ rats (p < 0.001). Blood levels of total cholesterol, low-density lipoprotein (LDL), and malondialdehyde (MDA), a marker for oxidative stress, were significantly decreased in both L-norvaline- and L-norvaline+L-arginine-treated HFD/STZ rats when compared with untreated rats. In addition, administration of L-norvaline and L-arginine reversed the progression of pancreatic and kidney pathology in HFD/STZ rats as assessed by histology (p < 0.001). ConclusionsBoth L-norvaline and L-arginine act as potent antihyperglycemic agents and can represent alternative therapeutic tools in individuals with hyperglycemia and pre-diabetes.

Contribution of CYP19A1, CYP1A1, and CYP1A2 polymorphisms in coronary heart disease risk among the Chinese Han population.

The previous study has pointed to that endogenous CYP metabolites play an important role in the pathogenesis of coronary heart disease (CHD). The study aimed to identify the association of CYP19A1, CYP1A1, and CYP1A2 polymorphisms with CHD susceptibility in a Chinese Han population. A total of 960 genetically unrelated participants consist of 480 CHD patients and 480 healthy controls were enrolled. Nine SNPs in CYP19A1, CYP1A1, and CYP1A2 were randomly selected and genotyped using the Agena MassARRAY platform. Logistic regression analysis was used for the relationship between selected SNPs and CHD susceptibility by calculating odds ratios (OR) with 95% confidence intervals (CI) adjusted for age and gender. The distribution of clinical characteristics in different genotypes was evaluated by one-way analysis of variance (ANOVA). CYP1A2 rs2470890 TT genotype had a higher CHD risk compared with CC genotype (OR = 3.06, p = 0.032) or CC-CT genotype (OR = 3.04, p = 0.033). Moreover, the contribution of CYP19A1 and CYP1A2 polymorphisms to CHD susceptibility was associated with age, gender, and clinical phenotypes (course of the disease and Gensini score). Besides, CYP1A2 rs762551 was related to serum levels of red blood cell, triglyceride, total cholesterol, and low-density lipoprotein cholesterol (LDL-C, p < 0.05). Our findings provided scientific evidence about CYP19A1, CYP1A1, and CYP1A2 polymorphisms on CHD incidence.

Trends & predictors of non-AIDS comorbidities among people living with HIV and receiving antiretroviral therapy in Lebanon.

Combined antiretroviral therapy (cART) increased the life expectancy of people living with Human Immunodeficiency Virus (HIV) (PLHIV) and remarkably reduced the morbidity and mortality associated with HIV infection. Consequently, PLHIV are experiencing non-acquired immunodeficiency syndrome (AIDS) associated comorbid conditions including diabetes, hyperlipidemia, hypertension, and cardiovascular disease. The aim of this study is to determine the frequency of non-AIDS associated comorbid conditions among a cohort of PLHIV on cART in Lebanon.Data were collected between November 2018 and December 2019 from 105 voluntary participants. A standardized questionnaire was used to collect demographic and behavioral data including lifestyle, smoking, physical activity, substance use and abuse in addition to co-infections and family history of non-communicable diseases. Moreover, data on occurrence and treatment of cardiovascular disease, hypertension, diabetes, lipid and metabolic disorders as well as mental health were collected. Blood samples were used to assess the levels of fasting blood sugar (FBS), glycosylated hemoglobin (HbA1C), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein, total cholesterol, and serum creatinine.Hypertension (29.5%) and hyperlipidemia (29.5%) followed by diabetes (23.7%) and cardiovascular disease (9.7%) were mainly reported among study participants. Higher rate of comorbid conditions was observed among participants >40 years of age than those ≤40 years with both hypertension and hyperlipidemia most commonly reported. Older age (odds ratio [OR] 7.6; 95% CI: 1.83-31.98; P = .005) is associated with higher odds of having hyperlipidemia. Moreover, participants on cART for ≥10 years are 5 times more likely to have hyperlipidemia (OR 5; 95% CI: 1.08-22.73; P = .039). Our results also showed that study participants did not experience anxiety, depression or somatic symptoms and that there was no association between these mental disorders and older age or comorbidities.Our results provide important information on HIV trends and associated comorbidities in Lebanon and can be used to improve the management of non-communicable diseases among PLHIV.

Effectiveness of a self-management education program on hypertension control and contributing factors in older adults: an interventional trial

Background: One of the common disorders that may negatively affect the health status in elderly is hypertension. Self-management education offers an effective method to control various disorders. This study was designed to assess the effectiveness of self-management educational program on blood pressure, and other cardiometabolic risk factors control among elderly patients from Tabriz, Iran. Material and methods: 227 eligible hypertensive elderly patients from three primary health care centers of Tabriz participated in 12 sessions of self-management education intervention conducted in 6 months from April to October 2019. Systolic (SBP) and diastolic blood pressure (DBP), serum levels of fasting blood sugar (FBS), total cholesterol (TC), and triglyceride, as well as anthropometric indices were assessed both before and at the end of the intervention. Results: The participants were 64.5 ± 5.8 years of age (mean ± SD). After 6-month attendance in educational sessions, the SBP (p = 0.04), body weight (p = 0.01), body mass index (BMI) (p = 0.02), FBS (p = 0.01), and TC (p &lt; 0.0001) were lower as referred to baseline. Conclusion: Study suggests self-management education programs in elderly may be beneficial for cardiovascular risk factors control.

Evaluation of pharmacist-led structured counselling on glycemic control and clinical outcomes of Type 2 diabetes mellitus patients at a health centre in East Jakarta, Indonesia

Background: The researchers developed structured counselling for Type 2 diabetes mellitus (T2DM) patients, comprised of an introduction to T2DM and how to manage it and its complications. Aim: This study aimed to evaluate structured counselling on its ability to improve glycemic control and the clinical outcomes of T2DM outpatients. Methods: A quasi-experimental study was conducted from August to December 2019 involving T2DM patients at health centers in East Jakarta, who met the criteria and had completed informed consent. The patients were divided into the intervention group (IG, n = 33), which received counselling and booklets, and the control group (CG, n = 32), which received booklets. Results: Counselling showed significant results in decreasing HbA1c levels and improving fasting blood glucose (FBG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c) levels in the IG compared to the CG. Moreover, counselling in the IG reduced HbA1c 7.596 times more than in the CG. Conclusion: Pharmacist-led structured counselling significantly improves glycemic control and clinical outcomes in T2DM patients.

The Traditional Chinese Medicine Hua Tuo Zai Zao Wan Alleviates Atherosclerosis by Deactivation of Inflammatory Macrophages.

Introduction Positive effects have been observed when the traditional Chinese medicine Hua Tuo Zai Zao Wan (HTZZW) has been used for the treatment of atherosclerosis (AS), although with an unclear mechanism. Methods ApoE-/- C57/BALB mice were used to determine the efficacy of HTZZW by blood lipid biochemical analysis and histopathology H&E staining. qPCR and western blot were used to determine the expression of METTL3/14 and NF-κB. Results High-fat diet-fed ApoE-/- mice that consumed HTZZW exhibited significantly smaller plaque areas and significantly decreased unstable collagen areas in the aortic arch as well as significantly lower blood levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol compared with the control group. Consumption of HTZZW significantly decreased the proportion of Mφ1 in the peripheral blood. HTZZW not only inhibited the expression of m6A methyltransferases METTL14, METTL3, and overall RNA methylation level, but it also decreased the m6A modification level on specific sites of NF-κB mRNA. Conclusion HTZZW significantly alleviated the progression of AS by regulating the expression of the m6A methyltransferases METTL14 and METTL3 in macrophages, eliminating m6A modifications of NF-κB mRNA, influencing the stability of NF-κB mRNA, and ultimately resulting in the deactivation of inflammatory macrophages.

Structural equation modeling to identify the direct and indirect risk factors of diabetes in adults: Findings from a national survey

BackgroundFew previous studies have investigated the multiple pathways that contribute to diabetes mellitus (DM) because of the complex, simultaneous interplay of attributing covariates. Structural equation modelling (SEM) is a robust multivariate approach that measures both direct and indirect effects of variables by simultaneously utilizing several regression equations. The current study applied SEM to test a hypothesized model of the covariates affecting DM among the adult population of the Sultanate of Oman. MethodsData from a large nationally representative 2017 WHO STEPwise approach to surveillance survey were analyzed. Stata 16 software was used to perform SEM and path analysis of the sociodemographic, behavioral, anthropometric, and metabolic variables affecting normoglycemia and DM. A priori factor structure was hypothesized with special emphasis on observing direct and indirect effects, and the correlations that defined them. ResultsEight paths that directly affected DM status were established based on eight sociodemographic, metabolic, and behavioral variables (age, sex, educational status, physical activity level, body mass index, waist-to-hip ratio, systolic blood pressure, and family history of DM). The remaining variables (marital status, employment status, smoking, high-density lipoprotein level, total blood cholesterol level, fruit and vegetable intake, and type of oil used for cooking) showed variable indirect effects. ConclusionsThe results of this study further reinforce the evidence that lifestyle changes are vital for the prevention and control of DM. Individuals with a family history of DM and a high waist-to-hip ratio comprise a high-risk group and should be targeted with screening and lifestyle-intervention programs.

Causal association evaluation of diabetes with Alzheimer's disease and genetic analysis of antidiabetic drugs against Alzheimer's disease

BackgroundDespite accumulating epidemiological studies support that diabetes increases the risk of Alzheimer’s disease (AD), the causal associations between diabetes and AD remain inconclusive. The present study aimed to explore: i) whether diabetes is causally related to the increased risk of AD; ii) and if so, which diabetes-related physiological parameter is associated with AD; iii) why diabetes drugs can be used as candidates for the treatment of AD. Two-sample Mendelian randomization (2SMR) was employed to perform the analysis.ResultsFirstly, the 2SMR analysis provided a suggestive association between genetically predicted type 1 diabetes (T1D) and a slightly increased AD risk (OR = 1.04, 95% CI = [1.01, 1.06]), and type 2 diabetes (T2D) showed a much stronger association with AD risk (OR = 1.34, 95% CI = [1.05, 1.70]). Secondly, further 2SMR analysis revealed that diabetes-related physiological parameters like fasting blood glucose and total cholesterol levels might have a detrimental role in the development of AD. Thirdly, we obtained 74 antidiabetic drugs and identified SNPs to proxy the targets of antidiabetic drugs. 2SMR analysis indicated the expression of three target genes, ETFDH, GANC, and MGAM, were associated with the increased risk of AD, while CPE could be a protective factor for AD. Besides, further PPI network found that GANC interacted with MGAM, and further interacted with CD33, a strong genetic locus related to AD.ConclusionsIn conclusion, the present study provides evidence of a causal association between diabetes and increased risk of AD, and also useful genetic clues for drug development.

Effect of synbiotic supplementation on asprosin level in high fat diet-induced metabolic disorder in pregnant rats

Synbiotic supplementation can improve metabolic disorders. The aim of this study was to assess the impact of synbiotic supplementation on the levels of asprosin, lipid profile, glucose, and insulin resistance in pregnant rats fed a high-fat diet (HFD). Rats were divided into three groups: control group (fed base chow), HFD group, and HFD + synbiotic group. Levels of blood glucose, total cholesterol, triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), insulin, and asprosin levels were measured. Birth weight of offspring in the HFD + synbiotic group was significantly lower than in the HFD group. Similarly, serum asprosin, insulin, insulin resistance, TG and total cholesterol levels in the HFD + symbiotic group were significantly lower than in the HFD group. Asprosin levels had a significant and positive correlation between food intake in the first ten days of the experiment and gestation period, fasting blood sugar (FBS), TG, and homeostatic model assessment (HOMA) index. Moreover, asprosin levels had a significant and negative correlation with HDL and insulin levels. Results showed, synbiotic supplementation has beneficial effects on obese animals and improves weight gain during pregnancy, pup birth weight, FBS, insulin resistance and lipid profile. These advantages of synbiotic supplementation could be mediated by reducing serum asprosin levels.

Atherogenic Index of Plasma and Its Association with Risk Factors of Coronary Artery Disease and Nutrient Intake in Korean Adult Men: The 2013-2014 KNHANES.

Coronary artery disease (CAD) has been linked to one of the highest death rates globally. The atherogenic index of plasma (AIP) may be an important predictor of atherosclerosis and cardiovascular disease, superior to the standard atherosclerotic lipid profile. This study investigated the relationship between AIP and obesity indices, blood glucose, lipid profile, and nutrient intake status in Korean adult men. The study included 1292 males aged ≥19 years old who participated in the Korea National Health and Nutrition Examination Survey, 2013–2014. Participants were divided into four groups according to AIP quartiles, calculated as log (triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C)). Body mass index, waist circumference, fasting blood glucose, hemoglobin A1c, total cholesterol, TG, and low-density lipoprotein cholesterol levels increased as AIP levels increased, whereas HDL-C level declined. As the level of AIP increased, intake of saturated fatty acid, calcium, phosphorus, riboflavin, milk, and dairy product decreased significantly, and the contribution rate of milk and dairy products to fat intake decreased. AIP was linked to obesity indices, blood glucose, and blood lipid profile in Korean men, suggesting that it could predict CAD.

The Chinese medicine Fufang Zhenzhu Tiaozhi capsule protects against renal injury and inflammation in mice with diabetic kidney disease

Ethnopharmacological relevanceFufang Zhenzhu Tiaozhi capsule (FTZ) is a patented preparation of Chinese herbal medicine that has been used to treat hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and other glucolipid metabolic diseases (GLMDs) in the clinic for almost 10 years. However, how FTZ reduces albuminuria and attenuates diabetic kidney disease (DKD) progression is unknown. Aim of the studyTo clarify the effects of FTZ on DKD mice model and to explore the underlying mechanisms. Materials and methodsWe used streptozotocin (STZ) (40 mg/kg/d, i.p. for 5 days, consecutively) combined with a high-fat diet (HFD) to induce a DKD mouse model, followed by FTZ (1, 2 g/kg/d, i.g.) treatment for 12 weeks. Losartan (30 mg/kg/d, i.g.) was used as a positive control. Measurements of 24 h proteinuria, serum creatinine (SCr), fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels and expression levels of fibronectin (FN), collagen IV, inflammatory cytokines, inflammatory cells, interleukin-17A (IL-17A) and the nuclear transcription factor-κB (NF-κB) signaling pathway in the kidney were examined. ResultsFTZ effectively decreased 24 h proteinuria, Scr, FBG, TC, TG, and LDL-C levels, inhibited mesangial cell expansion, reduced FN and collagen IV accumulation, and F4/80+ macrophage cell infiltration and Ly-6G+ neutrophil infiltration in glomerulus and tubulointerstitium. Furthermore, IL-17A production and the NF-κB signaling pathway were also downregulated after the administration of FTZ. ConclusionFTZ might attenuate DKD progression, and inhibited kidney inflammation and fibrosis by inhibiting the expression of RORγT and IL-17A in vivo, offering novel insights for the clinical application of FTZ.

Genetic association between miR-27a and miR-449b polymorphisms and susceptibility to diabetes mellitus.

Various mutations in microRNAs (miRs) are associated with the pathogenesis of several diseases including cancers and vascular diseases. The present study aimed to investigate the potential association between miR-27a A>G (rs895819) and miR-449b A>G (rs10061133) polymorphisms with the prevalence of type 2 diabetes mellitus (T2DM), and its associated risk factors in the Korean population. Genotype analysis was performed using PCR-restriction fragment length polymorphism analysis to assess the frequency of miR-27a and miR-449b gene polymorphisms in patients diagnosed with T2DM (n=238) and healthy controls (n=247). The miR-27a GG genotype, recessive model, and G allele were significantly associated with a decreased risk of T2DM [adjusted odds ratio (AOR)=0.378, 95% confidence interval (CI): 0.208-0.686, P=0.001; AOR=0.425, 95% CI: 0.246-0.734, P=0.002; AOR=0.640, 95% CI: 0.493-0.831, P=0.001, respectively). Although the miR-449b polymorphism was not associated with the prevalence of T2DM, the genotype and allele combination analyses for miR-27a and miR-449b polymorphisms showed associations with T2DM prevalence. Furthermore, stratification analysis revealed that the miR-27a polymorphism was associated with DM risk factors including body mass index (<28.12 kg/m2, P=0.031), waist circumference (<93.03 cm, P=0.036), systolic blood pressure (<132.67 mmHg, P=0.017), fasting blood glucose levels (<106.26 mg/dl, P=0.015), glycosylated hemoglobin, type A1C (≤125.5 mg/dl, P=0.001), total cholesterol (≤240 mg/dl, P=0.010) and low-density lipoprotein levels (≤130 mg/dl, P=0.028). The present study revealed an association between miR-27a A>G and miR-449b A>G polymorphisms and the risk of DM in Koreans, which suggests that these gene polymorphisms could represent potential markers for predicting T2DM risk.

Adipose Dysfunction in Adulthood Insulin Resistance of Low-Birth Weight Mice: A Proteomics Study.

PurposeTo investigate changes in the protein expression profile of white adipose tissue in low-birth weight (LBW) mice with high-fat diets using tandem mass tag (TMT) and liquid chromatography-mass spectrometry (LC-MS/MS) and parallel reaction monitoring (PRM).MethodsInstitute of Cancer Research (ICR) mice were used to establish an LBW model using malnutrition during pregnancy. Male pups were randomly selected from LBW and normal-birth weight (NBW) offspring, then all given a high-fat diet. Blood glucose, serum insulin, total cholesterol (TC) and triglyceride (TG) levels were measured. The weight ratio of liver, muscle, and adiposity index were calculated. Hematoxylin and eosin staining was used to visualize adipose tissue morphology. Oil red O staining of liver and TG content of muscle were used to determine ectopic lipid deposition. TMT combined with LC-MS/MS was used to analyze protein expression in white adipose tissue. PRM and Western blot were used to verify the expression of CD36, SCD1, PCK1 and PPARγ.ResultsCompared with NBW mice, fasting blood glucose, insulin and HOMA-IR significantly increased in LBW mice, indicating insulin resistance and impaired glucose regulation; TC, TG, adipocyte size, and adiposity index were increased in LBW mice, suggesting obesity and disorder of lipid metabolism. We observed ectopic lipid deposition in liver and muscle. There were 996 differentially expressed proteins (DEPs) in the LBW/NBW groups. Peroxisome proliferator-activated receptor (PPAR) was a relatively important signaling pathway regulating metabolic process in functional enrichment analysis of DEPs. Up-regulated expression of CD36, SCD1, and PCK1 in the adipose tissue of LBW mice was observed through PPAR pathways cluster analysis. And PRM and Western blot assay validated the proteomics findings.ConclusionWhen exposed to high-fat diets, LBW mice exhibited insulin resistance and disorder of lipid metabolism compared with NBW mice. The expression of PPARγ was elevated, as well as upstream CD36, downstream SCD1 and PCK1 of the PPARγ in the adipose tissue of LBW mice. It was suggested that the activation in CD36/PPARγ/SCD1 and CD36/PPARγ/PCK1 pathways may induce adipose dysfunction, thereby increasing susceptibility to insulin resistance.

The influence of SLC22A3 rs543159 and rs1317652 genetic variants on metformin therapeutic efficacy in newly diagnosed patients with type 2 diabetes mellitus: 25 weeks follow-up study

Background and aimsAmong anti-diabetic medications, metformin has been proven to be the preferred initial pharmacologic agent for type 2 diabetes mellitus (T2DM) treatment. Despite its safety and efficacy, the response to metformin varies between individuals. Genetic variations, especially within genes involved in pharmacokinetics and pharmacodynamics of metformin (e.g SLC22A3), have been suggested to be responsible for the observed inter-individual differences. By considering the undeniable role of organic cation transporter 3 in hepatic uptake of metformin, this study was aimed to investigate the association of rs543159 and rs1317652 variants in SLC22A3 gene with response to metformin monotherapy in newly diagnosed patients with T2DM. MethodsThe study included 200 T2DM patients who received metformin monotherapy for 25 weeks. The patients were classified into 2 groups according to their HbA1c values: the responders (reduction in HbA1c levels by at least 1% after 25 weeks treatment with metformin) and non-responders (less than 1% reduction in HbA1c levels after 25 weeks treatment with metformin). We used tetra ARMS-PCR method to determine genotypes of the target variants. ResultsFor the rs543159, CA and AA genotypes were more frequent in responders as compared to non-responders (OR = 2.48; 95% CI = 1.28–4.78, P-value = 0.0057) under the dominant model. In case of rs1317652 CC and CT genotypes were more frequent in metformin responders as compared to non-responder group (OR = 2.49; 95% CI = 1.32–4.70, P-value = 0.0043) under the dominant model. Parameters such as fasting blood sugar (FBS), HbA1c, and total cholesterol (TC) levels were significantly lower in the responder group after 25 weeks of metformin monotherapy. Moreover, according to the result of multiple linear regression rs543159 and base line HbA1c values are significantly associated with response to metformin monotherapy. ConclusionOur results suggested that rs543159 and rs1317652 in SLC22A3 gene might be associated with variability in response to metformin therapy in T2DM patients.

Phytochemical profile and antidiabetic effect of the bioactive fraction of Cirsium setidens in streptozotocin-induced type 2 diabetic mice

The current study investigated the phytochemicals profile, antioxidant activity, enzyme inhibition, and antidiabetic effects of the solvent fractions hexane fraction (HF-CS), ethyl acetate fraction (EAF-CS) and methanol fraction (MF-CS) obtained from the methanolic extract of Cirsium setidens (CS). The HPLC/MS analysis indicated that EAF-CS had significantly more content of syringin, rutin, nicotiflorin, isorhamnetin-3-O-rutinoside, isorhamnetin glucopyranoside, linarin, pectolinarigenin, and pectolinarin compared to the other two fractions. Similarly, the EAF-CS had a greater amount of total phenolic content (236.72 mg TAE/g extract) and total flavonoid content (137.15 mg QE/g extract). MF-CS had the highest DPPH scavenging activity among the fractions, with a lower inhibitory concentration (IC50) of 45.14 g/mL. However, the EAF-CS had a lower IC50 value for enzyme inhibition. EAF-CS (25 g/mL) treatment increased glucose uptake (80%) in insulin-resistant hepatocellular carcinoma cells (IR-HepG2) by reversing the insulin resistance. Biochemicalassays indicated that EAF-CS exerted its anti-diabetic effect by eliminating streptozotocin (STZ) induced diabetic status and restoring blood glucose, insulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels in STZ-induced diabetic mice. This was accomplished by recovering organs and limiting STZ-induced oxidative stress. Moreover, in-silico docking experiments indicated that the compounds in the EAF-CS synergistically inhibited α-amylase and α-glucosidase. Overall, the results of this study indicate that the EAF-CS might be used to purify a new antidiabetic agent.