scholarly journals Berberine Improves High-Fat Diet Induced Atherosclerosis and Hepatic Steatosis in Apoe-/-Mice by Down-Regulating PCSK9 via ERK1/2 Pathway

2020 ◽  
Author(s):  
Chun-Yan Ma ◽  
Xiao-Yun Shi ◽  
Ya-Ru Wu ◽  
Yue Zhang ◽  
Hui-Lin Qu ◽  
...  
Keyword(s):  
Western Blotting ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Density Lipoprotein ◽  
Atp Binding ◽  
Type I ◽  
High Fat ◽  
Atp Binding Cassette Transporter ◽  
Atp Binding Cassette

Abstract Background:Berberine (BBR) is a kind of alkaloid derived from Chinese herbal medicine, which has multiple pharmacological activities including anti-atherosclerosis (AS). However, the mechanism underlying the role of BBR in modulating lipid metabolic disorders is not fully clear. The aim of the present study was to investigate the beneficial effects of BBR on AS in ApoE-/- mice and its potential mechanisms.Methods: Eight-week old ApoE-/- mice with high-fat diet (HFD) and wild type mice were administered eitherBBR (50mg/kg/d and 100mg/kg/d, respectively) or equivoluminal saline. After the 16-week treatment, the blood was collected for lipid evaluation, and aorta and liver were obtained from the mice for hematoxylin-eosin (HE) staining, oil red O staining and Western blotting. HepG2 Cells were treated by BBR (0, 5, 25, and 50 μg/ml) for 24 hours. Real-time PCR or Western blotting was used to examine the expression levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), LDL receptor (LDLR), ATP-binding cassette transporter A1(ABCA1), ATP-binding cassette transporter G1(ABCG1) and scavenger receptor class B type I(SR-BI).Results: BBR significantly decreased serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) level in ApoE-/- mice fed with HFD. Moreover, BBR markedly reduced aorta atheroscleroticplaque, ameliorated lipid deposition in the liver in vivo. BBR could also promote intracellular cholesterol efflux and regulate LDLR and PCSK9 expression via the ERK1/2 pathway in HepG2 cells.Conclusions: BBR could improve lipid metabolism, decrease aorta AS and hepatic lipid accumulation in ApoE-/- mice fed with HFD, which was associated with down-regulation of PCSK9 through ERK1/2 pathway.

scholarly journals Reduced Plasma High-Density Lipoprotein Cholesterol in Hyperthyroid Mice Coincides with Decreased Hepatic Adenosine 5′-Triphosphate-Binding Cassette Transporter 1 Expression

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3708-3712 ◽  
Author(s):  
Ivan Tancevski ◽  
Andreas Wehinger ◽  
Egon Demetz ◽  
Philipp Eller ◽  
Kristina Duwensee ◽  
...  
Keyword(s):  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Atp Binding ◽  
Type I ◽  
Hepatic Expression ◽  
Atp Binding Cassette Transporter ◽  
Scavenger Receptor Class ◽  
Class B ◽  
Plasma High Density ◽  
Atp Binding Cassette

The aim of the study was to investigate the influence of severe hyperthyroidism on plasma high-density lipoprotein cholesterol (HDL-C). Recently, it was shown in mice that increasing doses of T3 up-regulate hepatic expression of scavenger receptor class B, type I, resulting in increased clearance of plasma HDL-C. Here, we show that severe hyperthyroidism in mice did not affect hepatic expression of scavenger receptor class B, type I, but reduced hepatic expression of ATP-binding cassette transporter 1, accompanied by a 40% reduction of HDL-C. The sterol content of bile, liver, and feces was markedly increased, accompanied by up-regulation of hepatic cholesterol 7α-hydroxylase, and ATP-binding cassette transporter 5, which is known to promote biliary sterol secretion upon dimerization with ATP-binding cassette transporter 8. Both control and hyperthyroid mice exerted identical plasma clearance of iv injected [3H]HDL-C, supporting the view that severe hyperthyroidism does not affect HDL-C clearance but, rather, its formation via hepatic ATP-binding cassette transporter 1.

scholarly journals Adipose Tissue ATP Binding Cassette Transporter A1 Contributes to High-Density Lipoprotein Biogenesis In Vivo

Circulation ◽  
2011 ◽  
Vol 124 (15) ◽  
pp. 1663-1672 ◽  
Author(s):  
Soonkyu Chung ◽  
Janet K. Sawyer ◽  
Abraham K. Gebre ◽  
Nobuyo Maeda ◽  
John S. Parks
Keyword(s):  
Adipose Tissue ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Atp Binding ◽  
Atp Binding Cassette Transporter ◽  
Atp Binding Cassette

The role of 5-HT7 receptors on isoproterenol-induced myocardial infarction in rats with high-fat diet exacerbated coronary endothelial dysfunction

2020 ◽  
Vol 39 (8) ◽  
pp. 1005-1018 ◽  
Author(s):  
I Cinar ◽  
Z Halici ◽  
B Dincer ◽  
B Sirin ◽  
E Cadirci
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Dysfunction ◽  
High Fat Diet ◽  
Density Lipoprotein ◽  
Heart Tissue ◽  
High Fat ◽  
Inflammatory Status

The presence of 5-HT7r’s in both human and rat cardiovascular and immune tissues and their contribution to inflammatory conditions prompted us to hypothesize that these receptors contribute in acute myocardial infarction (MI) with underlying chronic endothelial dysfunction. We investigated the role of 5-HT7 receptors on heart tissue that damaged by isoproterenol (ISO)-induced MI in rats with high-fat diet (HFD). In vitro and in vivo effects of 5-HT7r agonist (LP44) and antagonist (SB269970) have been investigated on the H9C2 cell line and rats, respectively. For in vivo analyses, rats were fed with HFD for 8 weeks and after this period ISO-induced MI model has been applied to rat. To investigate the role of 5-HT7r’s, two different doses of LP44 and SB269970 were evaluated and compared with standard hypolipidemic agent, atorvastatin. In vitro studies showed that LP44 has protective and proliferative effects on rat cardiomyocytes. Also in in vivo studies stimulating 5-HT7r’s by LP44 improved blood lipid profile (decreased total cholesterol, low-density lipoprotein-C, and triglyceride, increased high-density lipoprotein), decreased cardiac damage markers (creatine kinase and troponin-I), and corrected inflammatory status (tumor necrosis factor-α, interleukin-6). Our results showed significant improvement in LP44 administered rats in terms of histopathologic analyses. In damaged tissues, 5-HT7 mRNA expression increased and agonist administration decreased this elevation significantly. We determined for the first time that 5-HT7r’s are overexpressed in ISO-induced MI of rats with underlying HFD-induced endothelial dysfunction. Restoration of this overexpression by LP44, a 5-HT7r agonist, ameliorated heart tissue in physiopathologic, enzymatic, and molecular level, showing the cardiac role of these receptors and suggesting them as future potential therapeutic targets.

scholarly journals Anti-Obesity Effect of Diphlorethohydroxycarmalol Isolated from Brown Alga Ishige okamurae in High-Fat Diet-Induced Obese Mice

Marine Drugs ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. 637 ◽  
Author(s):  
Yuling Ding ◽  
Lei Wang ◽  
SeungTae Im ◽  
Ouibo Hwang ◽  
Hyun-Soo Kim ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Body Weight Gain ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Epididymal Adipose Tissue ◽  
High Fat ◽  
Expression Levels ◽  
Ishige Okamurae

Diphlorethohydroxycarmalol (DPHC) is one of the most abundant bioactive compounds in Ishige okamurae. The previous study suggested that DPHC possesses strong in vitro anti-obesity activity in 3T3-L1 cells. However, the in vivo anti-obesity effect of DPHC has not been determined. The current study explored the effect of DPHC on high-fat diet (HFD)-induced obesity in C57BL/6J mice. The results indicated that oral administration of DPHC (25 and 50 mg/kg/day for six weeks) significantly and dose-dependently reduced HFD-induced adiposity and body weight gain. DPHC not only decreased the levels of triglyceride, low-density lipoprotein cholesterol, leptin, and aspartate transaminase but also increased the level of high-density lipoprotein cholesterol in the serum of HFD mice. In addition, DPHC significantly reduced hepatic lipid accumulation by reduction of expression levels of the critical enzymes for lipogenesis including SREBP-1c, FABP4, and FAS. Furthermore, DPHC remarkably reduced the adipocyte size, as well as decreased the expression levels of key adipogenic-specific proteins and lipogenic enzymes including PPARγ, C/EBPα, SREBP-1c, FABP4, and FAS, which regulate the lipid metabolism in the epididymal adipose tissue (EAT). Further studies demonstrated that DPHC significantly stimulated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in both liver and EAT. These results demonstrated that DPHC effectively prevented HFD-induced obesity and suggested that DPHC could be used as a potential therapeutic agent for attenuating obesity and obesity-related diseases.

scholarly journals ATP-Binding Cassette Transporter A1: A Cell Cholesterol Exporter That Protects Against Cardiovascular Disease

2005 ◽  
Vol 85 (4) ◽  
pp. 1343-1372 ◽  
Author(s):  
John F. Oram ◽  
Jay W. Heinecke
Keyword(s):  
Cardiovascular Disease ◽  
Density Lipoprotein ◽  
Deficiency Syndrome ◽  
Atp Binding ◽  
The Metabolic Syndrome ◽  
Atp Binding Cassette Transporter ◽  
A Cell ◽  
Cell Membrane Protein ◽  
Abca1 Protein ◽  
Atp Binding Cassette

Blood high-density lipoprotein (HDL) levels are inversely related to risk for cardiovascular disease, implying that factors associated with HDL metabolism are atheroprotective. One of these factors is ATP-binding cassette transporter A1 (ABCA1), a cell membrane protein that mediates the transport of cholesterol, phospholipids, and other metabolites from cells to lipid-depleted HDL apolipoproteins. ABCA1 transcription is highly induced by sterols, a major substrate for cellular export, and its expression and activity are regulated posttranscriptionally by diverse processes. Liver ABCA1 initiates formation of HDL particles, and macrophage ABCA1 protects arteries from developing atherosclerotic lesions. ABCA1 mutations can cause a severe HDL deficiency syndrome characterized by cholesterol deposition in tissue macrophages and prevalent atherosclerosis. Genetic manipulations of ABCA1 expression in mice also affect plasma HDL levels and atherogenesis. Metabolites elevated in individuals with the metabolic syndrome and diabetes destabilize ABCA1 protein and decrease cholesterol export from macrophages. Moreover, oxidative modifications of HDL found in patients with cardiovascular disease reduce the ability of apolipoproteins to remove cellular cholesterol by the ABCA1 pathway. These observations raise the possibility that an impaired ABCA1 pathway contributes to the enhanced atherogenesis associated with common inflammatory and metabolic disorders. The ABCA1 pathway has therefore become an important new therapeutic target for treating cardiovascular disease.

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