High Density Lipoprotein Cholesteryl Ester Research Articles

Efficacy and Mechanism of a Chinese Classic Prescription of Yueju in Treating Nonalcoholic Steatohepatitis and Protecting Hepatocytes from Apoptosis.

Yueju, a famous classic Chinese prescription, has been extensively used in treating depression syndromes for hundreds of years. Recent studies have reported that Yueju showed good effects in treating metabolic diseases, such as obesity and hyperlipidemia. Nonalcoholic steatohepatitis (NASH), which leads to cirrhosis and severe cardiovascular diseases, is closely linked to obesity and abnormal lipid metabolism. In this study, Yueju could decrease the levels of alanine aminotransferase, aspartate transaminase, triglyceride, cholesterol, and low-density lipoprotein-C but increase the high-density lipoprotein-C in the serum of the NASH rat model induced by high-fat and high-cholesterol diet. Yueju could alleviate hepatosteatosis by increasing the phosphorylation of acetyl-CoA carboxylase and inhibiting the expression of fatty acid synthase and stearoyl-CoA desaturase 1. Yueju downregulated the expression of α-smooth muscle actin and collagen type 1A1, ameliorating the liver fibrilization. Yueju could also protect the hepatocytes from apoptosis by upregulating antiapoptosis protein Bcl-2 and X-linked inhibitor of apoptosis protein and downregulating apoptotic proteins Bax and cleaved poly ADP-ribose polymerase. Thus, Yueju could improve liver function, regulate lipid metabolism, alleviate hepatosteatosis and fibrosis, and protect hepatocytes from apoptosis against NASH. Yueju may be used as an alternative effective medicine for NASH treatment.

Identification of Novel Compounds Enhancing SR-BI mRNA Stability through High-Throughput Screening.

Atherosclerosis is the pathological basis of most cardiovascular diseases. Reverse cholesterol transport (RCT) is a main mechanism of cholesterol homeostasis and involves the direct transport of high-density lipoprotein (HDL) cholesteryl ester by selective cholesterol uptake. Hepatic scavenger receptor class B member 1 (SR-BI) overexpression can effectively promote RCT and reduce atherosclerosis. SR-BI may be an important target for prevention or treatment of atherosclerotic disease. In our study, we inserted human SR-BI mRNA 3' untranslated region (3'UTR) downstream of the luciferase reporter gene, to establish a high-throughput screening model based on stably transfected HepG2 cells and to screen small-molecule compounds that can significantly enhance the mRNA stability of the SR-BI gene. Through multiple screenings of 25 755 compounds, the top five active compounds that have similar structures were obtained, with a positive rate of 0.19%. The five positive compounds could enhance the SR-BI expression and uptake of DiI-HDL in the hepatocyte HepG2. E238B-63 could also effectively extend the half-life of SR-BI mRNA and enhance the SR-BI mRNA and protein level and the uptake of DiI-HDL in hepatocytes in a time-dependent and dose-dependent manner. The structure-activity relationship analysis showed that the structure N-(3-hydroxy-2-pyridyl) carboxamide is possibly the key pharmacophore of the active compound, providing reference for acquiring candidate compounds with better activity. The positive small molecular compounds obtained in this study might become new drug candidates or lead compounds for the treatment of cardiovascular diseases and contribute to the further study of the posttranscriptional regulation mechanism of the SR-BI gene.

Sea Cucumber Stichopus japonicus Hydrolysate Alleviates Late-onset-hypogonadism in Aged SD Rats

Objective: We assessed the andropause (=male climacteric syndrome)-relief effects of the sea cucumber (Stichopus japonicus) samples in an in vivo animal model using aged male SD rats (24 weeks old). Methods: During the experimental period, G1 (control group) received saline, and G2, G3, and G4 were administered 250 mg/kg of sea cucumber hot water extract, sea cucumber fermented by Cordycepe mili-taris, and hydrolysate of sea cucumber, daily by oral gavage, respectively. After 4 weeks, the effects of male menopause and aging on vascular health were assessed by measuring the total cholesterol (TC), tri-glyceride (TG), high density lipoprotein-c (HDL-c), and low density lipoprotein-c (LDL-c) in the serum. Testosterone levels, the most important indicator in male menopause, were measured in the blood. Aspartate transaminase (AST) and alanine transaminase (ALT) levels were also measured in order to evaluate liver toxicity. Results: No animal deaths were observed due to the administration of the test substance during the experimental period. There were no significant differences observed in the body weight, TC, TG, LDL-c, AST, and ALT levels in all 4 groups. In the G2 and G4 groups, the HDL-c level was significantly increased as compared to the other groups. Testosterone levels were significantly increased in the G4 group compared to the other groups. Conclusion: Therefore, the hydrolysate of sea cucumber, at a moderate dose (ca. 2400 mg/day), could be used as a health functional food material or pharmaceutical material to alleviate symptoms of male andro-pause without any adverse effects.

Protective Effects of α-Lipoic Acid on Vascular Oxidative Stress in Rats with Hyperuricemia.

The aim of the present study was to observe the protective effects of α-lipoic acid (ALA) on vascular injury in rats with hyperuricemia (HUA). The ALA treatment groups (10, 30 and 90 mg/kg, respectively) were administered with ALA via gavage for 2 weeks. Subsequently, the levels of blood urea nitrogen (BUN), creatinine (CREA), uric acid (UA), total cholesterol (TC), high density lipoprotein-C (HDL-C) and low density lipoprotein-C (LDL-C) were measured; the activities of glutathione peroxidase (GSH-Px), catalase (CAT), malonaldehyde (MDA), superoxide dismutase (SOD) and xanthine oxidase (XOD) were also determined. The thoracic aorta of rats in each experimental group was observed under a light microscope; ultrastructural analysis was performed. SOD and CAT protein contents were investigated by Western blotting. The results revealed that: i) Compared with the model group, the levels of UA were decreased in the ALA groups and the levels of BUN, CREA, TC, and LDL-C decreased in the 30 and 90 mg/kg ALA groups (P<0.05); ii) compared with the model group, the activities of GSH-Px, SOD and XOD were increased and the levels of MDA were reduced in the 90 mg/kg ALA group (P&lt;0.05); and iii) in the model and 10 mg/kg ALA groups, edema and shedding were observed in endothelial cells. Compared with the model and 10 mg/kg ALA groups, the 30 and 90 mg/kg ALA groups exhibited fewer swollen endothelial cells. In summary, the results of the present study indicated that HUA resulted in vascular oxidative stress injury and decreased the activity of antioxidative enzymes, which leads to endothelial cell damage and vascular lesions. ALA may serve as a therapeutic agent for the treatment of HUA-induced endothelial dysfunction.

Associations of oxytocin with metabolic parameters in obese women of childbearing age.

The aim of this study was to compare plasma oxytocin levels in obese women of childbearing age with non-obese women of childbearing age, and to investigate the relationship between plasma oxytocin levels and metabolic parameters (including blood glucose, insulin resistance, blood lipid, and blood pressure). A total of 151 obese women of childbearing age and 160 non-obese women of childbearing age were enrolled in this study. Plasma oxytocin levels were measured by electrochemiluminescence immunoassays. Height, body weight, body mass index (BMI), fasting blood glucose (FBG), fasting insulin (FI), homeostasis model assessment for insulin resistance (HOMA-IR), total triglycerides (TG), total cholesterol (TC), low-density lipoprotein-C (LDL-C), high-density lipoprotein-C (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured in all subjects. Quantile regression analysis was used to analyse the associations of plasma oxytocin levels with FBG, FI, HOMA-IR, TG, TC, LDL-C, HDL-C, SBP, and DBP. In obese women of childbearing age, plasma oxytocin levels were lower compared with non-obese controls. After adjusting for age, quantile regression analysis showed that the plasma oxytocin levels were inversely associated with HOMA-IR at the quantile level between 0.27 and 0.79 (i.e. the HOMA-IR level of 2.11 and 3.07, respectively), the plasma oxytocin levels were inversely associated with TC after the quantile level of 0.21 (i.e. the TC level of 3.78 ), and the plasma oxytocin levels were inversely associated with LDL-C at all quantile levels of LDL-C. In addition, the plasma oxytocin levels showed a positive association with HDL-C at all quantile levels of HDL-C. No significant associations were found between the plasma oxytocin levels and FBG, FI, TG, SBP, and DBP. Oxytocin deficiency was common in obese women of childbearing age. Oxytocin showed negative correlation with HOMA-IR, TC, and LDL-C, while it showed positive association with HDL-C. Our findings suggest that oxytocin played an important role in inhibiting metabolic disorders associated with obesity in women of childbearing age.

Isopulegol Ameliorates Dyslipidemia by Modulating Adipokine Secretion in High Fat Diet / Streptozotocin Induced Diabetic Rats

The present study investigates the effect of isopulegol on adipokine secretion and dyslipidemia in high fat diet and streptozotocin (HFD/STZ) induced diabetic rats. Animals were made diabetic by feeding HFD for 4 wks followed by single intraperitoneal injection of STZ (35mg/kg b.w; 0.1M citrate buffer; pH 4.0). Diabetic rats showed increased levels of total cholesterol, triglycerides, free fatty acids, phospholipids, low density lipoprotein-C (LDL-C), very low density lipoprotein -C (VLDL-C) and decreased high density lipoprotein-C levels (HDL-C). Similarly, the activity of HMG-CoA reductase, was increased while lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) activities were significantly decreased. Furthermore, the expression of sterol regulatory element binding protein-1C (SREBP-1C), adiponectin, peroxisome proliferator activated receptor gamma (PPARγ) were significantly down regulated, whereas leptin expression was upregulated in diabetic rats. Administration of isopulegol (100 mg/kg b.w) for 28 days significantly restored lipid levels in plasma and liver tissue by modulating adipokine secretion in diabetic treated rats. From this we conclude that isopulegol exhibited significant antihyperlipidemic effect in HFD/STZ induced diabetic rats. Keywords: Dyslipidemia, Diabetes mellitus, Adiponectin, Leptin, PPARγ, SREBP-1C

Simultaneous Determination of Biliary and Intestinal Cholesterol Secretion Reveals That CETP (Cholesteryl Ester Transfer Protein) Alters Elimination Route in Mice.

Determine the impact of CETP (cholesteryl ester transfer protein) on the route of cholesterol elimination in mice. Approach and Results: We adapted our protocol for biliary cholesterol secretion with published methods for measuring transintestinal cholesterol elimination. Bile was diverted and biliary lipid secretion maintained by infusion of bile acid. The proximal small bowel was perfused with bile acid micelles. In high-fat, high-cholesterol-fed mice, the presence of a CETP transgene increased biliary cholesterol secretion at the expense of transintestinal cholesterol elimination. The increase in biliary cholesterol secretion was not associated with increases in hepatic SR-BI (scavenger receptor BI) or ABCG5 (ATP-binding cassette G5) ABCG8. The decline in intestinal cholesterol secretion was associated with an increase in intestinal Niemann-Pick disease, type C1, gene-like 1 mRNA. Finally, we followed the delivery of HDL (high-density lipoprotein) or LDL (low-density lipoprotein) cholesteryl esters (CE) from plasma to bile and intestinal perfusates. HDL-CE favored the biliary pathway. Following high-fat feeding, the presence of CETP directed HDL-CE away from the bile and towards the intestine. The presence of CETP increased LDL-CE delivery to bile, whereas the appearance of LDL-CE in intestinal perfusate was near the lower limit of detection. Biliary and intestinal cholesterol secretion can be simultaneously measured in mice and used as a model to examine factors that alter cholesterol elimination. Plasma factors, such as CETP, alter the route of cholesterol elimination from the body. Intestinal and biliary cholesterol secretion rates are independent of transhepatic or transintestinal delivery of HDL-CE, whereas LDL-CE was eliminated almost exclusively in the hepatobiliary pathway.

Baru (Dipteryx alataVogel) almond and dairy desserts with baru regulates gastrointestinal transit in rats

The present study aimed to verify the antioxidant capacity in vitro of baru almond, evaluate the effect of baru intake on gastrointestinal transit and biochemical profile in rats and based on such results characterize the chemical composition of a baru-enriched dairy dessert and analyze its effect in vivo. It was observed that traditional dairy desserts hastened the gastric emptying and delayed intestinal transit. Ingestion of dairy dessert with baru slowed gastric emptying and avoided the delay of intestinal transit time. After baru consumption, the biochemical profile was extremely favorable with reduced triglycerides and very low-density lipoprotein, and increased high-density lipoprotein-c. The results show that baru almond is a good source of lipids, fibers, and antioxidants (1,179 mg GAE kg−1 sample by ABTS and 8,342 mg GAE kg−1 sample by ferric tripyridyltriazine). The dairy desserts with the highest content of baru normalized gastrointestinal transit compared to traditional dessert, and improved biochemical parameters in rats. Pratical applications In our work, we have developed a new dairy dessert with a Brazilian almond called Baru. The manuscript is significant because it demonstrates the presence of lipids, fibers, and antioxidants in high levels in baru almond and the health benefits associated with the intake of these compounds in dairy desserts.

Atorvastatin and Fenofibrate Increase the Content of Unsaturated Acyl Chains in HDL and Modify In Vivo Kinetics of HDL-Cholesteryl Esters in New Zealand White Rabbits.

Previous studies demonstrated modifications of high-density lipoproteins (HDL) structure and apolipoprotein (apo) A-I catabolism induced by the atorvastatin and fenofibrate combination. However, it remains unknown whether such structural and metabolic changes of HDL were related to an improvement of the HDL-cholesteryl esters (HDL-CE) metabolism. Therefore, we determined the structure of HDL and performed kinetic studies of HDL-CE radiolabeled with tritium in rabbits treated with atorvastatin, fenofibrate, and a combination of both drugs. The atorvastatin and fenofibrate combination increased the HDL size and the cholesterol and phospholipid plasma concentrations of the largest HDL subclasses. Moreover, the relative amount of unsaturated fatty acids contained in HDL increased, in detriment of saturated fatty acids as determined by gas chromatography–mass spectrometry. The transfers of cholesteryl esters (CE) from HDL to very low-density lipoproteins/low-density lipoproteins (VLDL/LDL) and vice versa were enhanced with atorvastatin, alone or in combination. Moreover, the direct elimination of CE from plasma via VLDL/LDL decreased with fenofibrate, whereas the direct elimination of CE via HDL augmented with the combination treatment. Taken together, the rise of unsaturated fatty acid content and the size increase of HDL, suggest that atorvastatin and fenofibrate induce more fluid HDL particles, which in turn favor an enhanced CE exchange between HDL and VLDL/LDL. Our results contribute to a better understanding of the relationship between the structure and function of HDL during the use of anti-dyslipidemic drugs.

Proline residues in scavenger receptor-BI's C-terminal region support efficient cholesterol transport.

High-density lipoproteins (HDLs) facilitate reverse cholesterol transport, a process in which HDL removes cholesterol from circulation and carries it to the liver for biliary excretion. Reverse cholesterol transport is also facilitated by HDL's high-affinity receptor, scavenger receptor-BI (SR-BI), by mechanisms that are not fully understood. To improve our understanding of SR-BI function, we previously solved the NMR (nuclear magnetic resonance) structure of a peptide encompassing amino acids 405–475 of SR-BI. This segment of SR-BI, that includes the functionally critical C-terminal transmembrane domain and part of the extracellular domain, also contains four conserved proline (Pro) residues. We hypothesized that these proline residues support SR-BI in a conformation that allows for efficient cholesterol transport. To test this, we generated individual Pro-to-alanine mutations in full-length SR-BI and transiently expressed the mutant receptors in COS-7 cells to measure the effects on SR-BI-mediated cholesterol transport functions. Our findings reveal that HDL cell association and uptake of HDL-cholesteryl esters are impaired by mutation of Pro-412, Pro-438, or the transmembrane proline kink residue (Pro-459). In addition, SR-BI-mediated cholesterol efflux and membrane cholesterol distribution are impaired by mutation of Pro-412 or Pro-438, indicating that these residues are essential for a fully functional SR-BI receptor. Furthermore, we demonstrate that Pro-408 is necessary for proper SR-BI expression, but mutation of Pro-408 does not cause SR-BI to become misfolded or rapidly degraded by the proteasome or the lysosome. We conclude that key proline residues play an important role in SR-BI function by allowing for the efficient transport of cholesterol between cells and HDL.

Liraglutide alters hepatic metabolism in high-fat fed obese mice: A bioinformatic prediction and functional analysis

Liraglutide, an important pharmacological agent used to improve glycemic status and weight control, has emerged as a therapeutic strategy for hepatic steatosis treatment. ObjectiveThe aim of the present study was to analyze the influence of liraglutide in hepatic steatosis and evaluate the potential target genes involved in the liraglutide action in the hepatic steatosis through a bioinformatics study. Methods & proceduresWe performed an animal study with male mice divided into three groups: standard, high-fat diet and the third group were fed a high-fat diet and treated with liraglutide at a dose of 0.6 mg/kg body weight. Blood parameters (glucose tolerance and insulin sensitivity tests, total cholesterol, high-density lipoprotein-C, triglycerides and glucose levels) were evaluated. mRNA analysis for ACC and FAS were performed. Gene databases, and bioinformatics algorithms were used to generate molecular targets for liraglutide and hepatic steatosis based on in silico investigation. Interactions networks between protein coding were accessed. ResultsThe present study showed that liraglutide decreased glucose levels, total cholesterol and triglycerides in obese animals as compared to the high-fat-fed obese mice. AKT and RPS6KB1 genes presented higher disease-related connectivity. Interaction Network exhibited a power law behavior in correlation: 0.896; R2: 0.796. Ontological analysis demonstrated different mechanisms associated such as regulation of signaling process. ConclusionThe present study reveals relevant information regarding the liraglutide effects in hepatic steatosis. The liraglutide improved hyperglycemia and attenuated hepatic steatosis in mice fed a high-fat diet.

HYDROALCOHOLIC EXTRACT OF MATRICARIA CHAMOMILLA LINN. AMELIORATES LIPIDS, LIPOPROTEINS, AND PARAOXONASE IN ISOPROTERENOL-INDUCED MYOCARDIAL INFARCTION IN WISTAR RATS

Objective: The objective of this study was to evaluate the effect of the hydroalcoholic extract of Matricaria Chamomilla Linn. (CHAE) on lipids, lipoproteins, and antioxidants activity in isoproterenol (ISO)-induced myocardial infarcted rats.&#x0D; Methods: ISO (85 mg/kg, s.c.)-induced myocardial infarction for 2 consecutive days at an interval of 24 h. Rats were pretreated with CHAE (100 and 200 mg/kg, oral) for a period of 20 days and ISO was injected on 21 and 22 days at 24 h intervals and after 24 h, blood was collected through retro-orbital plexus for the estimation of lipids, lipoproteins, and antioxidants assay.&#x0D; Results: In the present study, ISO caused a significant increase in the concentration of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), very LDL-C, and lipid peroxidation whereas a significant decrease in the concentration of high-density lipoprotein-C. ISO administration also significantly decreased the activities of paraoxonase (PON) enzyme. Oral pre-treatment of CHAE at doses of 100 and 200 mg/kg body weight (bw) for 20 days challenged with a concurrent injection of ISO (85 mg/kg bw) on 21 and 22 days significantly attenuated these alterations and restored the levels of lipids and lipoproteins. In addition, CHAE significantly elevated the serum antioxidants enzyme PON and catalase (CAT).&#x0D; Conclusion: The report revealed that pre-treatment with CHAE ameliorated lipid and lipoprotein and increased the antioxidant PON and CAT activity and decreased LPO level in ISO-treated male albino Wistar rats.

The serum level of a novel lipogenic protein Spot 14 was reduced in metabolic syndrome.

Spot 14 (S14) protein is primarily expressed in adipogenic tissues. Compared to wild type, S14 knockout mice had better resistance to diet-induced obesity and glucose tolerance. However, the association between serum S14 level and metabolic variables in humans has never been investigated. The objectives of this study were to evaluate the associations between serum S14 concentrations with components of metabolic syndrome (MetS). A total of 327 subjects were recruited in this cross-sectional study and categorized by presence of MetS. The mean serum levels of S14 were significantly lower in subjects with MetS than those without (87.1±26.3 μg/L vs. 107.3±40.2 μg/L, p<0.001). In addition, the subjects with central obesity, low high density lipoprotein-C (HDL-C) or hypertriglyceridemia also had significantly lower S14 levels in comparison to those without. Adjusted with age and sex, diagnosis of MetS (β = -0.227, p<0.001), central obesity (β = -0.176, p = 0.001), low HDL-C (β = -0.149, p = 0.005), and high triglyceride (TG) (β = -0.198, p<0.001) were negatively associated with log transformation of serum S14 levels (logS14). With 25% logS14 increased, the risk of MetS (OR 0.65, 95% CI, 0.51–0.82, p<0.001), central obesity (OR 0.72, 95% CI, 0.58–0.89, p = 0.002), low HDL-C (OR 0.76, 95% CI, 0.61–0.95, p = 0.015) or high TG (OR 0.65, 95% CI, 0.51–0.83, p = 0.001) was reduced with a dose response trend. Our analysis revealed that patients with MetS had lower serum S14 levels than those without. Negative associations existed between MetS, central obesity, high TG, low HDL-C and logS14.

EFFECT OF LIFESTYLE MODIFICATION IN TYPE II DIABETES MELLITUS INDIVIDUALS

Objectives: The objectives of this study were as follows: (1) To find the effect of conventional physiotherapy along with medications on Type II diabetes mellitus (DM) individuals and (2) to find the effect of lifestyle modification (LSM) and conventional physiotherapy with medications on Type II DM individuals.&#x0D; Methods: Ethical clearance was obtained from the institutional ethical committee. A total of 70 Type II DM individuals were assessed and 64 were included in this study based on inclusion criteria, the individuals were allocated into two groups: Group A (n=32) received conventional physiotherapy along with prescribed diabetic medications and Group B (n=32) received LSM and conventional physiotherapy with prescribed diabetic medications. Pre- and post-test were done for plasma glucose, serum insulin, glycated hemoglobin (HbA1c), total cholesterol, triglycerides, high-density lipoprotein-C, low-density lipoprotein by blood test, exercise tolerance by 6-min walk test, and quality of life (QOL) by SF-36 questionnaire, and the outcome measures were analyzed after 3 months.&#x0D; Results: Intergroup statistical analysis for HbA1c (p&lt;0.0001) and QOL (p&lt;0.0001) revealed extremely significant difference post-intervention. Analysis of HbA1c test for Group A (p=0.0652) was not significant and for Group B (p&lt;0.0001) was extremely significant. Moreover, QOL was significant for Group A (p=0.0004) as well as for Group B (p&lt;0.0001).&#x0D; Conclusion: The study results concluded that LSM was significantly effective in reducing HbA1c levels, exercise tolerance, plasma glucose, serum glycerine, and total cholesterol and improving QOL compared to conventional exercise.

Evaluation of Lipid Profile and Inflammatory Parameters in Female Diabetes Type 2 Induced Rabbits Treated with Glimepride, Bromocriptine and Fluoxtein

This study was performed to evaluate the improvement in serum lipid profile and inflammatory parameters in female diabetic rabbits after two-month treatment with glimepride, bromocriptine, and fluoxtein in order to decrease the cardiovascular disease risk related to type 2 diabetes mellitus. Twenty-five local female rabbits were divided equally into five groups; four groups were diabetes type 2 induced by alloxan 120 mg/kg and nicotinamide 50 mg/kg, and the fifth group was control negative (Cv-). The animals were allocated to different treatment regimens, dosed orally on a daily basis for two months, as follows: T1 (glimepride 0.11 mg/kg),T2 (glimepride 0.11+bromocriptine 0.04 mg/kg),T3 (glimepride 0.11+fluoxtein 0.29 mg/kg), control positive group(Cve+) diabetic without treatment, and the fifth group was a control negative group (Cve-) dosed with distall water. Lipid profile, interleukin-6, and C-reactive protein were determined after diabetes induction and at the end of the experiment. IL-6 was significantly reduced in T2, while C-Reactive Protein was not significantly reduced. All treated groups showed nearly similar total cholesterol levels, demonstrating the higher level of high density lipoprotein-C level . At the same time, all treated groups showed a non-significant decrease in low density lippoprotein-C, and T2 showed superiority in reducing very low density lipoprotein-C and triglyceride levels over all other diabetic groups. In conclusion, diabetes agonist (Bromocriptine)+glimepride demonstrated superiority over the combination therapy glimepride+flouxtein and glimepride as monotherapy in improving diabetes type 2 related cardiovascular complications.

Revisiting Reverse Cholesterol Transport in the Context of High-Density Lipoprotein Free Cholesterol Bioavailability.

Dysregulated free cholesterol (FC) metabolism has been implicated in nearly all stages of atherosclerosis, the underlying cause of most cardiovascular disease. According to a widely cited model, the burden of macrophage FC in the arterial wall is relieved by transhepatic reverse cholesterol transport (RCT), which comprises three successive steps: (1) macrophage FC efflux to high-density lipoprotein (HDL) and/or its major protein, apolipoprotein AI; (2) FC esterification by lecithin:cholesterol acyltransferase (LCAT); and (3) HDL-cholesteryl ester (CE) uptake via the hepatic HDL-receptor, scavenger receptor class B type 1 (SR-B1). Recent studies have challenged the validity of this model, most notably the role of LCAT, which appears to be of minor importance. In mice, most macrophage-derived FC is rapidly cleared from plasma (t1/2 < 5 min) without esterification by hepatic uptake; the remainder is taken up by multiple tissue and cell types, especially erythrocytes. Further, some FC is cleared by the nonhepatic transintestinal pathway. Lastly, FC movement among lipid surfaces is reversible, so that a higher-than-normal level of HDL-FC bioavailability-defined by high plasma HDL levels concurrent with a high mol% HDL-FC-leads to the transfer of excess FC to cells in vivo. SR-B1-/- mice provide an animal model to study the mechanistic consequences of high HDL-FC bioavailability that provokes atherosclerosis and other metabolic abnormalities. Future efforts should aim to reduce HDL-FC bioavailability, thereby reducing FC accretion by tissues and the attendant atherosclerosis.

Thyroid Dysfunction in Patients with Metabolic Syndrome: A Cross-Sectional, Epidemiological, Pan-India Study.

Background This study was conducted to assess the prevalence and clinical and epidemiological factors of thyroid dysfunction (TD) in Indian patients diagnosed with metabolic syndrome (MetS). Methods In this cross-sectional study, 432 adults with an established diagnosis of MetS were enrolled across ten centers in India. Anthropometric measurements and vital signs were noted. Blood samples were tested for hemogram, coagulogram, lipid profile, and thyroid function. Fasting plasma glucose (FPG) and fasting plasma insulin were used for the calculation of homeostasis model assessment-estimated insulin resistance (HOMA-IR). Overt hypothyroidism was defined as thyroid-stimulating hormone (TSH) > 4.50 μIU/mL with free thyroxine (FT4) < 0.8 ng/dL and free triiodothyronine (FT3) < 1.4 pg/mL; subclinical hypothyroidism as TSH > 4.50 μIU/mL with FT4 = 0.8-1.8 ng/dL and FT3 = 1.4-4.4 pg/mL; overt hyperthyroidism as TSH < 0.45 μIU/mL with FT4 > 1.8 ng/dL and FT3 > 4.4 pg/mL; and subclinical hyperthyroidism as TSH < 0.45 μIU/mL with FT4 = 0.8-1.8 ng/dL and FT3 = 1.4-4.4 pg/mL. Results About 121 out of 432 patients (28%) were diagnosed with TD (mean age ± SD: 47.9 ± 10.96 years), with women predominance (75% versus 25%). Most patients were in the >45 years of age group (men: 63%; women: 59%). TD was associated with high waist circumference (99.17%), reduced high-density lipoprotein-C (87.60%), raised HOMA-IR (86.78%), systolic blood pressure (77.69%), diastolic blood pressure (59.50%), fasting glucose (58.68%), and triglycerides (33.06%). Overt hypothyroidism was reported in 17.59% (N = 76) of patients. Subclinical hypothyroidism, overt hypothyroidism, and subclinical hyperthyroidism were reported in 8.10%, 1.60%, and 0.70% patients with newly occurred TD, respectively. No case of overt hyperthyroidism was present in these patients. Conclusion Hypothyroidism was the most common TD in Indian patients with MetS. A large proportion of TD cases diagnosed during the study highlight the need for vigilant thyroid screening in patients with MetS in a real-life setting.

The efficacy of double filtration plasmapheresis in the treatment of homozygous familial hypercholesterolemia: A single-center experience

IntroductionDifferent modalities of low-density lipoprotein (LDL) apheresis are used to treat patients with familial hypercholesterolemia (FH). The aim of this study was to describe the efficacy of the Double Filtration Plasmapheresis (DFPP) method for FH cases in our hands and to compare with other LDL apheresis techniques. Materials and methodsThis retrospective study was conducted between January 2016 and January 2018 in the University of Health Sciences, Diskapi Yildirim Beyazit Training and Research Hospital, Adult Hematology Clinic and Therapeutic Apheresis Unit. The study included 5 patients with a diagnosis of homozygous FH. A total of 288 DFFP procedures were performed twice a month (every 15 days) for 2 years. ResultsThe percentage reductions in Lipoprotein A, total cholesterol, Low Density Lipoprotein-C, High Density Lipoprotein-C and triglyceride levels were found to be 84%, 69.2%, 69.8%, 58.8% and 50.1% respectively (5 cases, n = 288). No cardiac event occurred after the initiation of LA with DFPP. ConclusionDFPP is an effective and safe LA method that can be used in the treatment of homozygous FH patients who do not respond to diet and statin therapy.

Incorporation of whole oat, especially bran, into a high-fat diet, improves cardio-metabolic risk factors in type 2 diabetic rats

PurposeThe purpose of this study was to determine the effects of whole oat, oat bran and refined oat incorporation in a high-fat diet (HFD) on cardio-metabolic risk biomarkers in rats with type 2 diabetes mellitus (T2DM).Design/methodology/approachT2DM was induced by feeding male rats with an HFD for 10 weeks, followed by a low dose of streptozotocin. T2DM rats were then divided into four homogeneous groups. Three groups consumed an HFD containing 45 per cent (g/100 g diet) whole oat, oat bran or refined oat. The fourth untreated group (control) received the HFD.FindingsThe results showed that whole oat and oat bran, compared with refined oat and control, effectively reduced food intake (p < 0.007), arterial blood pressure (p = 0.0001), glycemia (p < 0.001), insulinemia (p < 0.01), glycosylated haemoglobin (p < 0.001) as well as homeostasis insulin resistance (HOMA-IR) (p < 0.001). They also improved blood lipid levels and reverse cholesterol transport by reducing serum total cholesterol (p = 0.0001), triacylglycerols (p < 0.05), very-low- (p = 0.0001) and low-density lipoproteins cholesterol contents (p < 0.02) increasing lipids (p < 0.002) and cholesterol excretion (p = 0.0001), and high-density lipoprotein cholesteryl esters (HDL2-CE) concentrations (p = 0.0001) and stimulating lecithin: cholesterol acyltransferase (LCAT) activity (p = 0.0001). Moreover, they attenuated lipid peroxidation by increasing paraoxonase-1 (PON-1) atheroprotective activity (p < 0.05).Originality/valueIn T2DM rats, whole oat and particularly, its bran incorporated into an HFD improves arterial blood pressure, glycemic balance and lipid metabolic pathway by reducing hypertriglyceridemia and hypercholesterolemia and increasing atheroprotective activities of LCAT and PON-1. In contrast, refined oat accentuates the risk factors associated with diabetes.

Blood Metabolomic Measures Associate With Present and Future Glycemic Control in Type 2 Diabetes.

We studied whether blood metabolomic measures in people with type 2 diabetes (T2D) are associated with insufficient glycemic control and whether this association is influenced differentially by various diabetes drugs. We then tested whether the same metabolomic profiles were associated with the initiation of insulin therapy. A total of 162 metabolomic measures were analyzed using a nuclear magnetic resonance-based method in people with T2D from four cohort studies (n = 2641) and one replication cohort (n = 395). Linear and logistic regression analyses with adjustment for potential confounders, followed by meta-analyses, were performed to analyze associations with hemoglobin A1c levels, six glucose-lowering drug categories, and insulin initiation during a 7-year follow-up period (n = 698). After Bonferroni correction, 26 measures were associated with insufficient glycemic control (HbA1c >53 mmol/mol). The strongest association was with glutamine (OR, 0.66; 95% CI, 0.61 to 0.73; P = 7.6 × 10-19). In addition, compared with treatment-naive patients, 31 metabolomic measures were associated with glucose-lowering drug use (representing various metabolite categories; P ≤ 3.1 × 10-4 for all). In drug-stratified analyses, associations with insufficient glycemic control were only mildly affected by different glucose-lowering drugs. Five of the 26 metabolomic measures (apolipoprotein A1 and medium high-density lipoprotein subclasses) were also associated with insulin initiation during follow-up in both discovery and replication. The strongest association was observed for medium high-density lipoprotein cholesteryl ester (OR, 0.54; 95% CI, 0.42 to 0.71; P = 4.5 × 10-6). Blood metabolomic measures were associated with present and future glycemic control and might thus provide relevant cues to identify those at increased risk of treatment failure.