Two putative probiotic strains improve diet‐induced hypercholesterolemia through modulating intestinal cholesterol uptake and hepatic cholesterol efflux

2021 ◽  
Author(s):  
Hongsup Yoon ◽  
Yuri Lee ◽  
Hye‐Ji Kang ◽  
Jaehyun Ju ◽  
Yosep Ji ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Hepatic Cholesterol ◽  
Cholesterol Uptake ◽  
Probiotic Strains

scholarly journals Angptl4 Upregulates Cholesterol Synthesis in Liver via Inhibition of LPL- and HL-Dependent Hepatic Cholesterol Uptake

2007 ◽  
Vol 27 (11) ◽  
pp. 2420-2427 ◽  
Author(s):  
Laeticia Lichtenstein ◽  
Jimmy F.P. Berbée ◽  
Susan J. van Dijk ◽  
Ko Willems van Dijk ◽  
André Bensadoun ◽  
...  
Keyword(s):  
Cholesterol Synthesis ◽  
Hepatic Cholesterol ◽  
Cholesterol Uptake

Abstract 616: Interleukin 22 Downregulates ABCG1 and Impairs Cholesterol Efflux in Macrophages

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Marion Hofmann Bowman ◽  
Bijoy Chellan ◽  
Ling Yan ◽  
Timothy Sonntag ◽  
Catherine Reardon
Keyword(s):  
Protein Expression ◽  
Barrier Function ◽  
Cholesterol Efflux ◽  
Peritoneal Macrophages ◽  
Mouse Serum ◽  
Epithelial Barrier ◽  
Dependent Manner ◽  
Epithelial Barrier Function ◽  
Cholesterol Uptake ◽  
Mrna And Protein Expression

IL22 belongs to the IL10 cytokine family and is expressed by T helper cells. IL22 functions on epithelial cells and has been shown to improve epithelial barrier function in inflammatory bowel disease, asthma, and psoriasis; autoimmune diseases associated with elevated serum IL22. Patients with psoriasis have increased coronary artery disease and it was previously shown that macrophages from patients with psoriasis have impaired cholesterol efflux. The function of IL-22 on macrophage cholesterol metabolism is not known. Methods: ABCA1, ABCG1 and CD36 mRNA and protein expression, cholesterol uptake and efflux were studied in murine macrophages and human THP-1 macrophages. C57BL6/J mice with transgenic expression of hS100A12 and hS100A8/9 in myeloid cells were generated by using a bacterial artificial chromosome (hBAC/S100 mice). hBAC/S100 and WT littermate mice were breed into mice lacking the receptor for advanced glycation endproducts, RAGE. Results: Peritoneal macrophages from hBAC/S100 mice have reduced ABCG1 mRNA and protein expression, increased cholesterol uptake, and reduced cholesterol efflux compared to WT. This was abolished in hBAC/S100 mice lacking RAGE, the receptor for S100/calgranulin. Recombinant S100A12 or S100A8 protein (2.5 μg/ml) had no effect on ABCG1 expression in WT peritoneal macrophages or human THP-1 cells, suggesting other systemic intermediary products in hBAC/S100 mice. Serum IL22 and mRNA in splenic T cells were significantly increased in hBAC/S100 mice, and this was abolished in hBAC/S100 mice lacking RAGE. Moreover, r S100A12 increased IL22 mRNA by 2-fold in cultured human THP-1. Importantly, THP-1 macrophages treated with r IL22 (100 ng/ml) had reduced expression of ABCG1 and impaired cholesterol efflux to mouse serum, but not to Apoa1. Up regulation of ABCG1 and ABCA1 in response to LXR agonist TO901317 in THP-1 cells abolished the detrimental effects of IL22 on cholesterol efflux. Conclusion: S100/calgranulin induces IL22 in a RAGE dependent manner. IL22 down regulates ABCG1 and impairs cholesterol efflux in macrophages. This raises the hypothesis that IL22-mediated down regulation of cellular cholesterol efflux may be linked to improved epithelial barrier function, but may also augment atherosclerosis.

Abstract 65: Flavin Monoxygenase 3 (FMO3) is a Novel Regulator of Hepatic Cholesterol Metabolism and Transintestinal Cholesterol Efflux (TICE).

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Manya Warrier ◽  
Stepahie Marshall ◽  
Allison McDaniel ◽  
Martha Wilson ◽  
Amanda Brown ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Plasma Levels ◽  
Cholesterol Efflux ◽  
Cholesterol Metabolism ◽  
Transcriptional Profiling ◽  
Dietary Cholesterol ◽  
High Cholesterol Diet ◽  
Hepatic Cholesterol ◽  
Hepatic Expression ◽  
Cholesterol Levels

Recent studies have revealed a novel route for cholesterol disposal through intestine known as transintestinal cholesterol efflux (TICE) that significantly contributes to fecal neutral sterol loss. This pathway is an integral part of reverse cholesterol transport (RCT), yet major mechanisms regulating TICE are not well understood. Using an unbiased transcriptional profiling approach in mouse models of augmented TICE, we found that hepatic expression of the enzyme Flavin monoxygenase 3 (FMO3) was dramatically repressed. At the same time we identified this enzyme through transcriptional profiling, it was reported that plasma levels of its product trimethylamineoxide (TMAO) are highly predictive of atheroslcerosis in humans, and TMAO is proatherogenic in mice. To further understand FMO3’s role as a regulator of cholesterol metabolism we used antisense oligonucleotides (ASO) to knockdown FMO3 expression in mouse liver in C57BL/6 mice fed either low (0.02%) or high (0.2%) levels of dietary cholesterol. As expected, FMO3 knockdown (>90% knockdown in the liver) increased the TMA/TMAO ratio in plasma more than 3-fold. Interestingly, knockdown of FMO biliary cholesterol levels were reduced by 60%, whereas fecal cholesterol loss was quite normal in FMO3 ASO treated mice fed a high cholesterol diet, which phenocopies a previously described mouse model where TICE predominates (NPC1L1-liver transgenic mice). ASO-mediated knockdown of FMO3 also unexpectedly reduced hepatic cholesteryl ester (CE) storage by 70% in mice fed 0.2% cholesterol. In parallel, knockdown of FMO3 reduces plasma VLDL cholesterol levels and the secretion rate of VLDL cholesteryl ester, but not triacylglycerol in cholesterol fed mice. FMO3 knockdown also reduced the hepatic expression of several liver X receptor (LXR) target genes, while increasing expression of genes involved in cholesterol synthesis. Collectively, these studies have identified FMO3 as a novel regulator of hepatic cholesterol metabolism and TICE. Given that plasma levels of FMO3’s product (TMAO) are strongly associated with atherosclerosis development in humans, and production of TMAO promotes atherosclerosis in mice, these studies have important implications for future cardiovascular drug discovery.

Abstract 533: Salicylate Restores Macrophage Cholesterol Homeostasis via Activation of AMP-Activated Protein Kinase

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Morgan D Fullerton ◽  
Chelsea P McGregor ◽  
Nicholas D LeBlond ◽  
Shayne A Snider ◽  
Rebecca J Ford ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cholesterol Efflux ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Foam Cell ◽  
Cholesterol Homeostasis ◽  
Dependent Manner ◽  
Cholesterol Uptake ◽  
Gene And Protein Expression ◽  
Amp Activated Protein Kinase

Objectives: Atherosclerosis stems from imbalances in lipid metabolism and leads to maladaptive inflammatory responses. AMP-activated protein kinase (AMPK) is a highly conserved serine/threonine kinase that regulates many aspects of lipid and energy metabolism, although its specific role in controlling macrophage foam cell cholesterol homeostasis remains unclear. Methods: We sought to address this question by testing the effects of AMPK-specific activators in primary bone marrow-derived macrophages from AMPK β1-deficient (β1-/-) mice. Results: Macrophages from AMPK β1-/- mice had enhanced lipogenic potential and diminished cholesterol efflux, although cholesterol uptake was unaffected. Specific activation of Ampk β1 via salicylate (the unacetylated form of aspirin) or A-769662 (a small molecule activator), decreased the synthesis of both fatty acids and sterols in WT but not AMPK β1-/- macrophages. In lipid-laden macrophage foam cells, salicylate and A-769662 decreased cholesterol uptake and increased cholesterol efflux to HDL and apoA-I, effects that occurred in an AMPK β1-dependent manner. Increased cholesterol efflux was also associated with increased gene and protein expression of the ATP binding cassette transporters, ABCG1 and ABCA1. Moreover, in vivo reverse cholesterol transport was significantly suppressed in mice that received AMPK β1-/- macrophages compared to WT control. Conclusion: Our data highlight the therapeutic potential of targeting macrophage AMPK with new or existing drugs for the restoration of cholesterol homeostasis during the early stages of atherosclerosis.

scholarly journals The Effects of High Hydrostatic Pressure Extract of Mulberry Fruit on Hepatic Cholesterol Metabolism in Rats (P06-013-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jaerin Lee ◽  
Soojin Lee ◽  
Mak-Soon Lee ◽  
Yoonjin Lee ◽  
Jiyeon Kim ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Cholesterol Metabolism ◽  
High Cholesterol Diet ◽  
Atp Binding ◽  
Mrna Levels ◽  
Cholesterol Diet ◽  
Hepatic Cholesterol ◽  
High Cholesterol ◽  
Mulberry Fruit ◽  
Atp Binding Cassette

Abstract Objectives The objective of this study is to investigate the effects of high hydrostatic pressure (HHP) extract of mulberry fruit on the regulation of hepatic cholesterol metabolism in high-cholesterol diet fed rats. Methods Male Sprague-Dawley rats(6-week-old) were randomly divided into 5 groups, and fed with a normal diet (NOR), High cholesterol diet (HC), HC supplemented with 0.4% mulberry (ML) or 0.8% mulberry (MH) and HC treated with statin (ST) for 4 weeks. Results The HHP extract of mulberry fruit did not affect body weight gain and food intake and reduced the serum and liver lipids in the mulberry supplemented groups (ML, MH). In this study, we found that the HHP extract of mulberry fruit changed the level of genes involved in hepatic cholesterol metabolism. In the MH group, the mRNA levels of apolipoprotein A-1 (apoA-1), ATP-binding cassette transporter A1 (ABCA1) and lecithin-cholesterol acyltransferase (LCAT), which are involved in hepatic HDL biogenesis, were significantly increased by 1.80-, 1.77- and 2.65-fold, respectively, compared with the HC group. The MH group also significantly upregulated mRNA levels of cholesterol efflux related gene such as the liver X receptor α (LXRα), ATP-binding cassette protein G5 (ABCG5) and ATP-binding cassette protein G8 (ABCG8) compared to the HC group in the liver tissue. ABCG5 and ABCG8 expression levels of the MH group were also higher than those of the ST group. The mRNA level of cholesterol 7a-hydroxylase (CYP7A1), which is bile acid synthetic rate-limiting enzyme was higher in the MH group than that of the HC group. Furthermore, the immunohistochemical staining intensity became evident for CYP7A1 in liver of the MH group. Conclusions These results suggest at least partial involvement of HDL cholesterol synthesis, cholesterol efflux and bile acid synthesis in HHP extract of mulberry fruit mediated beneficial effects on hepatic cholesterol metabolism. Funding Sources None.

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.

Quercetin regulates hepatic cholesterol metabolism by promoting cholesterol-to-bile acid conversion and cholesterol efflux in rats

2016 ◽  
Vol 36 (3) ◽  
pp. 271-279 ◽  
Author(s):  
Min Zhang ◽  
Zongkai Xie ◽  
Weina Gao ◽  
Lingling Pu ◽  
Jingyu Wei ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholesterol Efflux ◽  
Cholesterol Metabolism ◽  
Hepatic Cholesterol

Cultured gallbladder epithelial cells synthesize apolipoproteins A-I and E

2003 ◽  
Vol 285 (3) ◽  
pp. G630-G641 ◽  
Author(s):  
Jin Lee ◽  
Aimee Tauscher ◽  
Dong Wan Seo ◽  
John F. Oram ◽  
Rahul Kuver
Keyword(s):  
Epithelial Cells ◽  
Intracellular Trafficking ◽  
Cholesterol Efflux ◽  
Hormone Receptors ◽  
Gallstone Formation ◽  
Retinoid X Receptor ◽  
Biliary Cholesterol ◽  
Cholesterol Uptake ◽  
Model Bile ◽  
Apoe Mrna

Gallbladder epithelial cells (GBEC) are exposed to high and fluctuating concentrations of biliary cholesterol on their apical (AP) surface. GBEC absorb and efflux cholesterol, but the mechanisms of cholesterol uptake, intracellular trafficking, and efflux in these cells are not known. We previously reported that ATP binding cassette (ABC)A1 mediates basolateral (BL) cholesterol efflux in cultured polarized GBEC. In addition, the nuclear hormone receptors liver X receptor (LXR)α and retinoid X receptor (RXR) mediate both AP and BL cholesterol efflux. An interesting finding from our previous study was that apolipoprotein (apo)A-I applied to the AP surfaces of cells elicited BL ABCA1-mediated cholesterol efflux. Because ABCA1-mediated cholesterol efflux requires the presence of a cholesterol acceptor, we hypothesized that GBEC synthesize and secrete endogenous apo into the BL compartment. Here, we demonstrate that cholesterol loading of cells with model bile and AP apoA-I treatment is associated with an increase in the synthesis of apoE mRNA and protein. Furthermore, apoE is secreted into the BL compartment. LXRα/RXR ligands stimulate the synthesis of endogenous apoA-I mRNA and protein, as well as apoE mRNA. BL secretion of apoA-I is elicited by LXRα/RXR ligands. Therefore, GBEC synthesize apoA-I and -E and efflux cholesterol using ABCA1- and non-ABCA1- mediated pathways. These processes may alter gallbladder biliary cholesterol concentrations and thereby influence gallstone formation.

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