scholarly journals Hepatic expression of cholesterol regulating genes favour increased circulating low-density lipoprotein in HIV infected patients with gallstone disease: a preliminary study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Suman Mewa Kinoo ◽  
Anil A. Chuturgoon ◽  
Bugwan Singh ◽  
Savania Nagiah
Keyword(s):  
Antiretroviral Therapy ◽  
Cholesterol Efflux ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Gallstone Disease ◽  
Density Lipoprotein ◽  
Hiv Positive ◽  
Related Disorder ◽  
Hepatic Expression ◽  
Sub Saharan

Abstract Background HIV endemic populations are displaying higher incidence of metabolic disorders. HIV and the standard treatment are both associated with altered lipid and cholesterol metabolism, however gallstone disease (a cholesterol related disorder) in Sub-Saharan African populations is rarely investigated. Methods This study sought to evaluate hepatic expression of key genes in cholesterol metabolism (LDLr, HMGCR, ABCA1) and transcriptional regulators of these genes (microRNA-148a, SREBP2) in HIV positive patients on antiretroviral therapy presenting with gallstones. Liver biopsies from HIV positive patients (cases: n = 5) and HIV negative patients (controls: n = 5) were analysed for miR-148a and mRNA expression using quantitative PCR. Results Circulating total cholesterol was elevated in the HIV positive group with significantly elevated LDL-c levels(3.16 ± 0.64 mmol/L) relative to uninfected controls (2.10 ± 0.74 mmol/L; p = 0.04). A scavenging receptor for LDL-c, LDLr was significantly decreased (0.18-fold) in this group, possibly contributing to higher LDL-c levels. Transcriptional regulator of LDLr, SREBP2 was also significantly lower (0.13-fold) in HIV positive patients. Regulatory microRNA, miR-148a-3p, was reduced in HIV positive patients (0.39-fold) with a concomitant increase in target ABCA1 (1.5-fold), which regulates cholesterol efflux. Conclusions Collectively these results show that HIV patients on antiretroviral therapy display altered hepatic regulation of cholesterol metabolizing genes, reducing cholesterol scavenging, and increasing cholesterol efflux.

scholarly journals Hepatic Expression of Cholesterol Regulating Genes Favour Increased Circulating Low-Density Lipoprotein in HIV Infected Patients With Gallstone Disease: A Preliminary Study

2020 ◽  
Author(s):  
Suman Kinoo ◽  
Anil Chuturgoon ◽  
Bugwan Singh ◽  
Savania Nagiah
Keyword(s):  
Antiretroviral Therapy ◽  
Cholesterol Efflux ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Gallstone Disease ◽  
Density Lipoprotein ◽  
Hiv Positive ◽  
Related Disorder ◽  
Hepatic Expression ◽  
Sub Saharan

Abstract Background: HIV endemic populations are displaying higher incidence of metabolic disorders. HIV and the standard treatment are both associated with altered lipid and cholesterol metabolism, however gallstone disease (a cholesterol related disorder) in Sub-Saharan African populations is rarely investigated. Methods: This study sought to evaluate hepatic expression of key genes in cholesterol metabolism (LDLr, HMGCR, ABCA1) and transcriptional regulators of these genes (microRNA-148a, SREBP2) in HIV positive patients on antiretroviral therapy presenting with gallstones. Liver biopsies from HIV positive patients (cases: n=5) and HIV negative patients (controls: n=5) were analysed for miR-148a and mRNA expression using quantitative PCR.Results: Circulating total cholesterol was elevated in the HIV positive group with significantly elevated LDL-c levels(3.16±0.64mmol/L) relative to uninfected controls (2.10±0.74mmol/L; p=0.04). A scavenging receptor for LDL-c, LDLr was significantly decreased (0.18-fold) in this group, possibly contributing to higher LDL-c levels. Transcriptional regulator of LDLr, SREBP2 was also significantly lower (0.13-fold) in HIV positive patients. Regulatory microRNA, miR-148a-3p, was reduced in HIV positive patients (0.39-fold) with a concomitant increase in target ABCA1 (1.5-fold), which regulates cholesterol efflux. Conclusions: Collectively these results show that HIV patients on antiretroviral therapy display altered hepatic regulation of cholesterol metabolizing genes, reducing cholesterol scavenging and increasing cholesterol efflux.

scholarly journals High-Fructose Diet-Induced Hypertriglyceridemia Is Associated With Enhanced Hepatic Expression of ACAT2 in Rats

2019 ◽  
pp. 1021-1026 ◽  
Author(s):  
Y. Ichigo ◽  
A. Takeshita ◽  
M. Hibino ◽  
T. Nakagawa ◽  
T. Hayakawa ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Serum Levels ◽  
Diet Group ◽  
High Fructose Diet ◽  
Hepatic Expression ◽  
Protein Levels ◽  
High Fructose

High levels of fructose induce hypertriglyceridemia, characterized by excessive levels of triglyceride-rich lipoproteins such as very low-density lipoprotein (VLDL); however, the underlying mechanisms are poorly understood. The aim of this short communication was to examine hepatic changes in the expression of genes related to cholesterol metabolism in rats with hypertriglyceridemia induced by high-fructose or high-glucose diets. Rats were fed a 65 % (w/w) glucose diet or a 65 % (w/w) fructose diet for 12 days. Serum levels of triglycerides, total cholesterol, and VLDL+LDL-cholesterol, hepatic levels of triglycerides and cholesterol, and ACAT2 expression at the gene and protein levels were significantly higher in the fructose diet group compared to the glucose diet group. The hepatic levels of Abcg5/8 were lower in the fructose group than in the glucose group. Serum high-density lipoprotein (HDL)-cholesterol and hepatic expression levels of Hmgcr, Ldlr, Acat1, Mttp, Apob, and Cyp7a1 did not differ significantly between groups. These findings suggest that high-fructose diet-induced hypertriglyceridemia is associated with increased hepatic ACAT2 expression.

Polyphenols can Potentially Prevent Atherosclerosis and Cardiovascular Disease by Modulating Macrophage Cholesterol Metabolism

2020 ◽  
Vol 14 (2) ◽  
pp. 175-190 ◽  
Author(s):  
Fumiaki Ito
Keyword(s):  
Cholesterol Efflux ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Arterial Disease ◽  
Epidemiological Studies ◽  
Cholesterol Homeostasis ◽  
Cholesterol Accumulation ◽  
Cholesterol Uptake ◽  
Patients At Risk

Background: Arterial atherosclerosis is the main pathological cause of coronary artery disease and peripheral arterial disease. Atherosclerosis is a chronic condition characterized by the presence of cholesterol-rich macrophages in the arterial intima. Accumulation of cholesterol in these macrophages is due to increased oxidation of low-density lipoprotein (LDL) and its uptake via scavenger receptors on the macrophages. Cholesterol efflux from the cholesterol-laden macrophages into high-density lipoprotein (HDL) is also a key process in maintaining cholesterol homeostasis and prevention of cholesterol accumulation. Four pathways for the efflux of cholesterol to HDL exist in macrophages, including passive and active pathways. Several HDL characteristics determine cholesterol efflux capacity, namely composition, oxidative status, and HDL size. Oxidation of LDL and HDL as well as any imbalance in cholesterol uptake and efflux could lead to accumulation of cholesterol in macrophages and initiation of atherosclerogenesis. Conclusion: Epidemiological studies have demonstrated that polyphenol-rich foods reduce cardiovascular events in the general population and in patients at risk of cardiovascular diseases. Many studies have reported that polyphenols in polyphenol-rich foods have anti-atherosclerotic properties by preventing cholesterol accumulation in macrophages through the suppression of lipoproteins oxidation and regulation of cholesterol uptake and efflux.

Lipid Profile in HIV Infected Children Receiving Antiretroviral Treatment

2018 ◽  
Vol 3 (02) ◽  
Author(s):  
Dr. Kavita J. Lall ◽  
Dr. Omesh Khurana ◽  
Dr. Ranjit S Ambad
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Lipid Profile ◽  
Antiretroviral Treatment ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hiv Positive ◽  
Low Density ◽  
First Line ◽  
Immunodeficiency Virus

This study reviewed the lipid profile of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in relation to use of antiretroviral therapy (ART). Lipid profile is becoming one of the common problems in human immunodeficiency virus infected patients receiving antiretroviral therapy. Data on lipid profile derangements induced by antiretroviral treatment. The aim of this study was to assess the lipid profile abnormalities in HIV infected children receiving ART. Material and Method - Information on sex, age, specific ART type in use , ART start date, duration of treatment, duration of HIV infection, BMI, relevant signs and symptoms and medications if any were collected by trained nurses using structured questionnaires and patients medical record. Blood Sample Collection, Transport and Processing - Following a standard and safety collection procedure, about 5 ml fasting venous blood was taken from the patients and the control groups by clinical nurses and senior laboratory technologist. Fasting serum samples were analyzed for total cholesterol (TC), triglyceride (TG), High Density Lipoprotein- Cholesterol (HDL-c). Low density lipoprotein cholesterol (LDL) and Very low density lipoprotein (VLDL) was determined by Friedewald Equation (13).   Result and conclusion - There was statistically significant difference between the two groups for TC, TG, TC/HDL-c ratio and TG/HDL –c ratio. On the basis of our study we concluded that the level of TG, TC, HDL-c and VLDL-c is high in HIV positive populations receiving first line ART (group I) as compared to ART naïve (group II). Considering that these altered lipid profiles can be an independent risk factors for coronary artery diseases and myocardial infarction, treatment with first-line ART may actually have potential risks for cardiovascular health of HIV positive people receiving ART.

scholarly journals Gallstone Disease and Cholesterolosis in Monozygotic Twin Sisters

2007 ◽  
Vol 10 (1) ◽  
pp. 39-42
Author(s):  
R Ivanchenkova ◽  
N Sharashkina ◽  
I Martirosyan ◽  
S Limborska ◽  
A Ryskov
Keyword(s):  
Normal Tissue ◽  
Genetic Basis ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Gallstone Disease ◽  
Density Lipoprotein ◽  
Monozygotic Twin ◽  
Gallbladder Wall ◽  
Cholesterol Accumulation ◽  
Ldl Subfractions

Gallstone Disease and Cholesterolosis in Monozygotic Twin SistersGallstone disease and Cholesterolosis may be independent diseases or forms of the same disease, caused by impairment of cholesterol metabolism. Gallstone disease is characterized by formation of cholesterol concrements in the gallbladder cavity. Cholesterolosis is a hyperplastic cholecistosis, caused by cholesterol accumulation in the gallbladder wall with subsequent proliferation of gallbladder normal tissue elements. We describe monozygotic twin sisters, one of whom developed gallstone disease and the other developed cholesterolosis. Monozygosity was verified by a DNA fingerprinting method. Both had identical heterogeneity of plasma low density lipoprotein (LDL) subfractions, but associated with different functional conditions within the gallbladder. The different manifestations may be due to epigenetic, metabolic or environmental factors, since both had a common genetic basis.

A potent soluble epoxide hydrolase inhibitor, t-AUCB, modulates cholesterol balance and oxidized low density lipoprotein metabolism in adipocytes in vitro

2014 ◽  
Vol 395 (4) ◽  
pp. 443-451 ◽  
Author(s):  
Li Shen ◽  
Hongchun Peng ◽  
Shuiping Zhao ◽  
Danyan Xu
Keyword(s):  
Cholesterol Efflux ◽  
Epoxide Hydrolase ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Soluble Epoxide Hydrolase ◽  
Cholesterol Homeostasis ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein

Abstract The cholesterol metabolism in adipose tissue is dependent on the balance between cholesterol uptake and efflux. Adipocytes dysfunction and its cholesterol imbalance are associated with obesity. Adipocytes are the site for clearance of oxidized low density lipoprotein (oxLDL) in blood. Soluble epoxide hydrolase (sEH) is highly expressed in adipocytes. sEH converts epoxyeicosatrienoic acids (EETs) into less bioactive dihydroxyeicosatrienoic acids, which regulate cholesterol metabolism in adipocytes and block the development of atherosclerosis. In vitro, 3T3-L1 differentiated adipocytes were incubated with the sEH inhibitor t-AUCB (0, 1, 10, 50 or 100 mmol/l) for 24 h with or without the PPARγ inhibitor GW9662. To determine the effect of t-AUCB on oxLDL endocytosis, degradation and cholesterol efflux from adipocytes, we demonstrated that t-AUCB enhances the CD36-mediated recognition and degradation of oxLDL and improves cholesterol efflux via the upregulation of ABCA1 expression. Furthermore, t-AUCB blocked TNF-α secretion and increased adiponectin levels found in adipocytes culture medium. We provide evidence that these effects are PPARγ-dependent. These results suggest that an increase in EETs because of sEH inhibition could maintain cellular cholesterol homeostasis by the regulation of oxLDL clearance and cholesterol efflux via the EETs–PPARγ pathway.

scholarly journals Efficacy of Bilberry and Grape Seed Extract Supplement Interventions to Improve Glucose and Cholesterol Metabolism and Blood Pressure in Different Populations—A Systematic Review of the Literature

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1692
Author(s):  
Teresa Grohmann ◽  
Caroline Litts ◽  
Graham Horgan ◽  
Xuguang Zhang ◽  
Nigel Hoggard ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Ldl Cholesterol ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Grape Seed Extract ◽  
Grape Seed ◽  
Good Evidence ◽  
Seed Extract

Intervention with fruit extracts may lower glucose and lipid levels, as well as blood pressure. We reviewed the efficacy of bilberry and grape seed extracts to affect these outcomes across populations with varying health status, age and ethnicity, across intervention doses and durations, in 24 intervention studies with bilberry and blackcurrant (n = 4) and grape seed extract (n = 20). Bilberry and blackcurrant extract lowered average levels of glycated hemoglobin (HbA1c), at least in Chinese subjects, especially in those who were older, who were diagnosed with Type 2 Diabetes Mellitus (T2DM) and who were participating in longer-term studies. We also found good evidence that across studies and in subjects with hypercholesterolemia, T2DM or metabolic syndrome, intervention with bilberry and blackcurrant extract, and to some extent grape seed extract, significantly lowered total and low density lipoprotein (LDL) cholesterol levels after four weeks. Intervention with grape seed extract may reduce systolic and diastolic blood pressure in subjects with hypertension or metabolic syndrome. Differential responsiveness in cholesterol and blood pressure outcomes between stratified populations could not be explained by age, dose or study duration. In conclusion, bilberry and blackcurrant extract appears effective in lowering HbA1c and total and LDL cholesterol, whereas grape seed extract may lower total and LDL cholesterol, and blood pressure, in specific population groups.

scholarly journals Deleting myeloid IL-10 receptor signalling attenuates atherosclerosis in LDLR-/- mice by altering intestinal cholesterol fluxes

2016 ◽  
Vol 116 (09) ◽  
pp. 565-577 ◽  
Author(s):  
Gemma Brufau ◽  
Marion J. J. Gijbels ◽  
Ine M. J. Wolfs ◽  
Saskia van der Velden ◽  
Chantal C. H. Pöttgens ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Liver Cholesterol ◽  
Specific Cell ◽  
Low Density ◽  
Atherosclerosis Development ◽  
Deficient Mice

SummaryInflammatory responses and cholesterol homeostasis are interconnected in atherogenesis. Interleukin (IL)-10 is an important anti-inflammatory cytokine, known to suppress atherosclerosis development. However, the specific cell types responsible for the atheroprotective effects of IL-10 remain to be defined and knowledge on the actions of IL-10 in cholesterol homeostasis is scarce. Here we investigated the functional involvement of myeloid IL-10-mediated atheroprotection. To do so, bone marrow from IL-10 receptor 1 (IL-10R1) wild-type and myeloid IL-10R1-deficient mice was transplanted to lethally irradiated female LDLR-/- mice. Hereafter, mice were given a high cholesterol diet for 10 weeks after which atherosclerosis development and cholesterol metabolism were investigated. In vitro, myeloid IL-10R1 deficiency resulted in a pro-inflammatory macrophage phenotype. However, in vivo significantly reduced lesion size and severity was observed. This phenotype was associated with lower myeloid cell accumulation and more apoptosis in the lesions. Additionally, a profound reduction in plasma and liver cholesterol was observed upon myeloid IL-10R1 deficiency, which was reflected in plaque lipid content. This decreased hypercholesterolaemia was associated with lowered very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels, likely as a response to decreased intestinal cholesterol absorption. In addition, IL-10R1 deficient mice demonstrated substantially higher faecal sterol loss caused by increased non-biliary cholesterol efflux. The induction of this process was linked to impaired ACAT2-mediated esterification of liver and plasma cholesterol. Overall, myeloid cells do not contribute to IL-10-mediated atheroprotection. In addition, this study demonstrates a novel connection between IL-10-mediated inflammation and cholesterol homeostasis in atherosclerosis. These findings make us reconsider IL-10 as a beneficial influence on atherosclerosis.Supplementary Material to this article is available online at www.thrombosis-online.com.

Bile Acids: The Good, the Bad, and the Ugly

Physiology ◽  
1999 ◽  
Vol 14 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Alan F. Hofmann
Keyword(s):  
Bile Acids ◽  
Enterohepatic Circulation ◽  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Absorption ◽  
Bile Acid Metabolism ◽  
Cholesterol Levels ◽  
Density Lipoprotein Receptor

Bile acids, amphipathic end products of cholesterol metabolism, are “good” in the infant because they enhance lipid absorption and thereby promote growth. Bile acids also induce bile flow and biliary lipid secretion. The enterohepatic circulation of bile acids is “bad” in the adult because it downregulates hepatocyte low-density lipoprotein receptor activity and thereby elevates plasma cholesterol levels. Defects in bile acid metabolism such as impaired biosynthesis or transport are “ugly” because they cause morbidity and death. New approaches for treating these defects are being developed.

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