scholarly journals Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model

2016 ◽  
Vol 5 ◽  
Author(s):  
Haiqiu Huang ◽  
Zhuohong Xie ◽  
Wallace Yokoyama ◽  
Liangli Yu ◽  
Thomas T. Y. Wang
Keyword(s):  
High Fat Diet ◽  
Cholesterol Metabolism ◽  
Ldl Receptor ◽  
High Fat ◽  
Hamster Model ◽  
Hmg Coa Reductase ◽  
Cholesterol Levels ◽  
Reductase Mrna ◽  
Coa Reductase ◽  
The Relationship

AbstractHypercholesterolaemia is a risk factor for CVD, which is a leading cause of death in industrialised societies. The biosynthetic pathways for cholesterol metabolism are well understood; however, the regulation of circulating cholesterol by diet is still not fully elucidated. The present study aimed to gain more comprehensive understanding of the relationship between circulating cholesterol levels and molecular effects in target tissues using the hamster model. Male golden Syrian hamsters were fed with chow or diets containing 36 % energy from fat with or without 1 % cholesteyramine (CA) as a modulator of circulating cholesterol levels for 35 d. It was revealed that the expression of lanosterol 14α-demethylase (CYP51) instead of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase mRNA expression was responsive to circulating cholesterol in hamsters fed hypercholesterolaemic diets. The high-fat diet increased circulating cholesterol and down-regulated CYP51, but not HMG-CoA reductase. The CA diet decreased cholesterol and increased CYP51 expression, but HMG-CoA reductase expression was not affected. The high-fat diet and CA diet altered the expression level of cholesterol, bile acids and lipid metabolism-associated genes (LDL receptor, cholesterol 7α-hydroxylase (CYP7A1), liver X receptor (LXR) α, and ATP-binding cassette subfamily G member 5/8 (ABCG5/8)) in the liver, which were significantly correlated with circulating cholesterol levels. Correlation analysis also showed that circulating cholesterol levels were regulated by LXR/retinoid X receptor and PPAR pathways in the liver. Using the hamster model, the present study provided additional molecular insights into the influence of circulating cholesterol on hepatic cholesterol metabolism pathways during hypercholesterolaemia.

Short-term effects of ACTH on the low-density lipoprotein receptor mRNA level in rat and hamster adrenals

1991 ◽  
Vol 6 (3) ◽  
pp. 223-230 ◽  
Author(s):  
J.-G. Lehoux ◽  
A. Lefebvre
Keyword(s):  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Cholesterol Content ◽  
Low Density ◽  
Short Term ◽  
Hmg Coa Reductase ◽  
Receptor Mrna ◽  
Coa Reductase

ABSTRACT Low-density lipoprotein (LDL) receptor mRNA was found in both rat and hamster adrenals. Within 30 min after ACTH administration a significant increase in the levels of both LDL receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) mRNAs was observed in rat adrenals; these levels remained increased for up to 240 min. The increase in the levels of LDL receptor and HMG-CoA reductase mRNAs produced by ACTH was reduced by co-administration of aminoglutethimide while, at the same time, the adrenal cholesterol content of rats treated with both aminoglutethimide and ACTH was significantly increased compared with that in groups treated with ACTH alone. Cycloheximide also induced increased levels of rat adrenal mRNAs for LDL receptor and HMG-CoA reductase, but this effect was not additive with that of ACTH. These results suggest that, in the rat, the short-term effect of ACTH on the levels of mRNAs for the LDL receptor and HMG-CoA reductase is similarly controlled and might be mediated through changes in the adrenal cholesterol content. In the hamster adrenal, however, no significant fluctuations were found in the level of LDL receptor mRNA, although a marked increase was found in the level of HMG-CoA reductase mRNA, 2 h after ACTH administration. This indicates that an important effect of ACTH on cholesterol metabolism in the hamster adrenal is at the level of HMG-CoA reductase. In the hamster, therefore, where the main source of cholesterol for the adrenal gland is de-novo synthesis, it seems that a complex mechanism is involved in the control of LDL receptor gene expression.

Tetrahydrocurcumin: Beneficial Effects on HMG-CoA Reductase enzyme and Lipoprotein Lipase Enzymes in High-fat diet-induced Hypercholesteremia Rabbits

2012 ◽  
Vol 2 (2) ◽  
pp. 50-60 ◽  
Author(s):  
Kalavarasariel Gopinathanpillai ◽  
Eluri Kalpana ◽  
Balasubramaniam Dineshkumar ◽  
Elumalai Monogaran ◽  
Govindharajalu Geetha ◽  
...  
Keyword(s):  
Lipoprotein Lipase ◽  
High Fat Diet ◽  
High Fat ◽  
Hmg Coa Reductase ◽  
Beneficial Effects ◽  
Coa Reductase

PL-006 Expression of molecular markers of hepatic cholesterol metabolism are altered by a short-term high-fat diet

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Jean-Marc Lavoie
Keyword(s):  
Lipid Accumulation ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Hepatic Cholesterol ◽  
High Fat ◽  
Short Term ◽  
Cholesterol Levels ◽  
Ldl Particles

Objective Metabolic disorders are often associated with liver steatosis and increased plasma cholesterol levels. However, the link between excessive lipid accumulation and impairments in cholesterol metabolism remains uninvestigated in the liver. Hence, a short treatment with a high-fat diet (HFD) was previously shown to promote excessive lipid accumulation in liver prior to the development of metabolic disorders. The present study intended to characterize how increases in liver fat alter the expression of several key regulators of hepatic cholesterol metabolism in response to a short-term HFD. Methods Young Wistar rats were randomly submitted either to HFD (n = 8) or a regular chow diet (RCD; n = 8) for 14 days.Liver tissue and blood were sampled . Results Increases in triglycerides were highly significant (P< 0.01) in liver but marginal in plasma of HFD rats. In contrast, the HFD resulted in higher (P< 0.01) cholesterol levels in plasma but not in liver samples. Gene expression of key markers involved in cholesterol uptake (LDL particles) including low density lipoprotein receptor-related protein-1 (LRP-1) and protein convertase subtilisin/kexin type 9 (PCSK9) along with ATP-binding cassette, superfamily G, member 5 (ABCG5) involved in cholesterol exportation viabile ducts were found to be higher (P< 0.05) in response to the HFD. In contrast, expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), involved in cholesterol synthesis was down-regulated in liver Conclusions The data support the concept that excessive accumulation of lipids promptly alters the expression of key genes regulating cholesterol metabolism in liver. On a clinical point of view, this indicates that increases in plasma cholesterol occur after a short-term high fat diet.

scholarly journals Antihyperlipidemic Activity of Aloe succotrina in Rats: Possibly Mediated by Inhibition of HMG-CoA Reductase

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Dinesh Dhingra ◽  
Deepak Lamba ◽  
Ramesh Kumar ◽  
Pashupati Nath ◽  
Satyaprakash Gauttam
Keyword(s):  
High Fat Diet ◽  
The Body ◽  
Atherogenic Index ◽  
Heart Weight ◽  
Albino Rats ◽  
High Fat ◽  
Hmg Coa Reductase ◽  
Antihyperlipidemic Activity ◽  
Per Se ◽  
Coa Reductase

The present study was designed to investigate antihyperlipidemic activity of dried pulp of Aloe succotrina leaves in Wistar albino rats. Hyperlipidemia was induced in rats by feeding them high fat diet (HFD) or D-fructose (25% w/v) for 4 successive weeks. From 15th to 28th day, dried pulp (100 and 200 mg/kg, p.o) and atorvastatin (10 mg/kg, p.o.) per se were administered 2 h prior to feeding rats with HFD or fructose. Aloe succotrina did not significantly decrease the body weight of rats. The dried pulp and atorvastatin per se significantly decreased relative liver weight but did not significantly affect relative heart weight. HFD or fructose significantly increased serum total cholesterol, triglycerides, LDL-c, and VLDL, and decreased HDL-c; significantly increased liver MDA and decreased GSH levels. The dried pulp (200 mg/kg p.o.) significantly reversed high fat diet-induced and fructose-induced hyperlipidemia and atherogenic index. Aloe succotrina significantly decreased HMG Co-A reductase activity. Antihyperlipidemic effect of the dried pulp was comparable to atorvastatin. Thus, Aloe succotrina produced significant antihyperlipidemic activity in both HFD and fructose-induced hyperlipidemic rats, possibly through normalization of serum lipid profile, HMG-CoA reductase inhibitory activity, and amelioration of oxidative stress in liver.

scholarly journals Antihyperlipidemic and Antioxidant Effects of Averrhoa Carambola Extract in High-Fat Diet-Fed Rats

Biomedicines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 72 ◽  
Author(s):  
Saleem Aladaileh ◽  
Sultan Saghir ◽  
Kisantini Murugesu ◽  
Amirin Sadikun ◽  
Ashfaq Ahmad ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
High Fat Diet ◽  
Atherogenic Index ◽  
Antioxidant Defenses ◽  
Dependent Manner ◽  
High Fat ◽  
Hmg Coa Reductase ◽  
Averrhoa Carambola ◽  
Coa Reductase

The present study explored the antihyperlipidemic potential of a standardized methanolic extract of Averrhoa carambola (A. carambola) leaf (MEACL) in high-fat diet (HFD)-fed rats. The standardized MEACL was orally administered at different doses (250, 500, and 1000 mg/kg) to HFD-induced hyperlipidemic rats for five weeks. Serum lipid profile, body weight changes, body mass index (BMI), daily food intake, relative organ weight, and histology of the liver were evaluated. In addition, the effect of MEACL on HMG-CoA reductase and pancreatic lipase activities as well as hepatic and fecal lipids was demonstrated. MEACL supplementation reduced serum lipids in HFD-fed rats in a dose-dependent manner. Histopathological scores revealed that 1000 mg/kg MEACL restored the damage to liver tissue in hyperlipidemic rats. MEACL decreased the body mass index (BMI), atherogenic index, and hepatic cholesterol and triglycerides and increased fecal cholesterol and bile acids in HFD-fed rats. Also, MEACL ameliorated lipid peroxidation and improved antioxidant defenses in the liver of HFD-fed rats. Furthermore, HMG-CoA reductase and lipase were suppressed by MEACL. In conclusion, this study shows the potential effect of MEACL to ameliorate hyperlipidemia and oxidative stress in HFD-fed rats. It prevented hepatic lipid accumulation and exerted an inhibitory effect on HMG-CoA reductase and lipase.

scholarly journals Activation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase during high fat diet feeding

2013 ◽  
Vol 1832 (10) ◽  
pp. 1560-1568 ◽  
Author(s):  
Nan Wu ◽  
Lindsei K. Sarna ◽  
Sun-Young Hwang ◽  
Qingjun Zhu ◽  
Pengqi Wang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Coenzyme A ◽  
High Fat ◽  
Hmg Coa Reductase ◽  
Coa Reductase

scholarly journals The modulating effect of ferulic acid on high fat diet induced hyperlipidemia and obesity:A dose response study in male Sprague Dawleyrats

Biomedicine ◽  
2021 ◽  
Vol 41 (2) ◽  
pp. 413-420
Author(s):  
Mumtaz Khan Mohamed ◽  
V. Ramamurthy
Keyword(s):  
Body Weight ◽  
Ferulic Acid ◽  
High Fat Diet ◽  
Blood Lipids ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Serum Adiponectin ◽  
High Fat ◽  
Hmg Coa Reductase ◽  
Coa Reductase

Introduction and Aim: Ferulic acid (FA) is a phenolic compound predominantly found in cereals have been used in traditional Chinese medicine. Here, we studied the effect of FA on high-fat diet (HFD) induced hyperlipidemia and obesity in rats.   Materials and Methods:Hyperlipidemia was induced in male Sprague Dawley rats by feeding HFD for 14 weeks. The hypolipidemic effect was evaluated by co-administering 50,100, 200 and 250 mg/kg body weight of FA. At the end of the experimental period, rats were sacrificed and serum/plasma levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), aspartate transaminase (AST), alanine transaminase (ALT), 3-hydroxy-3methyl-glutaryl-coenzyme A reductase (HMG CoA reductase) and adiponectin were determined. Moreover, Histopathological examination of liver and visceral adipose tissue (AT) was also carried out.   Results:HFD treatment significantly increased weight gain, body mass index, total fat pad mass, blood lipids, LDL cholesterol and serum transaminases.HFD +FA fed rats showed a significant decrease in blood lipids and an increase in antioxidant enzymes when compared to the HFD control rats. The activity of HMG CoA reductase and serum adiponectin levels were elevated in rats administered with FA. Among the 4 doses studied, 200 mg of FA/kg body weight exhibited optimum hypolipidemic activity. Histological observations in the liver and visceral AT added additional evidence for the lipid-lowering effect of FA.   Conclusion:These findings indicate that FA can act as a hypolipidemic agent, probably by modulating the activity of HMG CoA reductase and serum adiponectin levels.

scholarly journals Mekanisme Katekin Sebagai Obat Antidislipidemia (Uji In Silico)

2018 ◽  
Vol 46 (3) ◽  
pp. 147-154 ◽  
Author(s):  
Rosa Adelina
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Cholesterol Metabolism ◽  
Ldl Receptor ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Hmg Coa Reductase ◽  
Action Mechanisms ◽  
In Silico Study ◽  
Coa Reductase

Indonesia has a large biodiversity that can be used as a medicinal plant, one of that is Gambir. The high content of catechin in gambir has the potential to be an antidyslipidemic drug. The mechanism of catechin as antidyslipidemic drug can be traced using a molecular docking study which is one of the studies of the in silico study model used to filter compounds based on their mechanism of action against target proteins. In this study, the molecular docking of catechin was done using Molecular on Environment Software (MOE) to identify the affinity and interaction with HMG-CoA reductase and LDL enzymes that contribute to fat/cholesterol metabolism. The results of molecular docking showed that catechin interaction against HMG-CoA reductase and LDL receptor enzymes had Gibbs value of -6,5758 kcal/mol and -16,1709 kcal/mol, respectively. Potential catechin action mechanisms as antidyslipidemic use two pathways, inhibition of HMG-CoA reductase enzyme and increased LDL receptor.   Abstrak  Indonesia memiliki kekayaan hayati yang besar dan dapat dimanfaatkan sebagai tanaman obat, salah satunya gambir. Kandungan senyawa katekin yang tinggi dalam gambir berpotensi sebagai antidislipidemia. Mekanisme katekin sebagai antidislipidemia dapat ditelusuri menggunakan studi docking molekuler yang merupakan salah satu studi model studi in silico yang digunakan untuk menapis senyawa berdasarkan mekanisme kerjanya terhadap protein target. Pada penelitian ini senyawa katekin dilakukan docking secara molekuler dengan menggunakan Software Moleculer on Environtment (MOE) dengan tujuan untuk mengetahui daya afinitas dan interaksinya terhadap enzim HMG-CoA reduktase dan reseptor LDL yang berperan terhadap metabolisme kolesterol. Hasil docking molekuler menunjukkan bahwa interaksi katekin terhadap enzim HMG-CoA reduktase dan reseptor LDL memiliki nilai Gibbs  masing-masing sebesar -6,5758 kacl/mol dan -16,1709 kcal/mol. Potensi mekanisme aksi katekin sebagai antidislipidemia menggunakan dua jalur yaitu penghambatan enzim HMG-CoA reduktase dan peningkatan reseptor LDL.  

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