Effects of dietary 27-hydroxycholesterol on cholesterol metabolism and bile acid biosynthesis in the hamster

2003 ◽  
Vol 81 (9) ◽  
pp. 854-863 ◽  
Author(s):  
Maâmar Souidi ◽  
Sandrine Dubrac ◽  
Michel Parquet ◽  
Fabien Milliat ◽  
Jacqueline Férézou ◽  
...  
Keyword(s):  
Bile Acid ◽  
Coenzyme A ◽  
Cholesterol Metabolism ◽  
Scavenger Receptor ◽  
Bile Acid Metabolism ◽  
Type I ◽  
Fourfold Increase ◽  
Hepatic Expression ◽  
Class B ◽  
Coenzyme A Reductase

27-hydroxycholesterol (27OH-Chol) is an important endogenous oxysterol resulting from the action of sterol 27-hydroxylase (CYP27A1) on cholesterol in the liver and numerous extrahepatic tissues. It may act as a modulator of cholesterol and bile acid metabolism. The effects of 27OH-Chol on the main enzymes and receptors of cholesterol metabolism were investigated by feeding male hamsters a diet supplemented with 27OH-Chol (0.1% w/w) for 1 week. Intestinal scavenger class B, type I (SR-BI) protein level was decreased (–65%), but hepatic expression was increased (+34%). Liver 3β-hydroxy-3β-methyl glutaryl coenzyme A reductase (–58%), cholesterol 7α-hydroxylase (–54%), oxysterol 7α-hydroxylase (–44%), and sterol 12α-hydroxylase (–70%) activities were all decreased. Bile acid composition was changed (fourfold increase in the chenodeoxycholic/cholic acid ratio). This study demonstrates that dietary 27OH-Chol modulates major enzymes of cholesterol metabolism and alters the biliary bile acid profile, making it more hydrophobic, at least at this level of intake. Its effects on SR-BI protein levels are organ dependent. The properties of 27OH-Chol or its metabolites on cholesterol metabolism probably result from the activation of specific transcription factors. Key words: cholesterol 7α-hydroxylase (CYP7A1), sterol 12α-hydroxylase (CYP8B1), sterol 27-hydroxylase (CYP27A1), 3β-hydroxy-3β-methyl glutaryl coenzyme A reductase (HMGCoAR), scavenger receptor class B type I (SR-BI).

Cholesterol Metabolism—Impacts on SARS-CoV-2 Infection Prognosis, Entry, and Antiviral Therapies

2020 ◽  
Author(s):  
Congwen Wei ◽  
Luming Wan ◽  
Yanhong Zhang ◽  
Chen Fan ◽  
Qiulin Yan ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Scavenger Receptor ◽  
Hdl Cholesterol ◽  
Lung Cells ◽  
Type I ◽  
Antiviral Therapies ◽  
Scavenger Receptor Class ◽  
Global Pandemic ◽  
Class B ◽  
Clinically Significant

AbstractThe recently emerged pathogenic SARS-coronavirus 2 (SARS-CoV-2) has spread rapidly, leading to a global pandemic. In this study, we show that SARS-CoV-2 infection was associated with clinically significant lower level of HDL cholesterol (HDL-C), which can be used as indicators of disease severity and poor prognosis. Importantly, we found the spike protein of SARS-CoV-2 (SARS-2-S) bound to HDL. Antagonists of HDL receptor-Scavenger receptor class B type I (SR-B1), strongly inhibited SARS-CoV-2 infection. Notably, the lipids transfer function of SR-B1 was indispensable for this inhibition, offering explanations for the reduced serum HDL level observed in COVID-19 patients. Basing on findings here, we speculate that SR-B1-mediated pulmonary HDL-vitamin E uptake could participate in mediating SARS-CoV-2 infection of lung cells, and the unique expression profile of SR-B1 may also affect SARS-CoV-2 cell and tissue tropism. These findings might help to provide further insights into viral transmission, pathological characteristics and reveal therapeutic targets.Graphical Abstract

scholarly journals Coordinate Regulation of Cholesterol and Bile Acid Metabolism by the Clock Modifier Nobiletin in Metabolically Challenged Old Mice

2019 ◽  
Vol 20 (17) ◽  
pp. 4281 ◽  
Author(s):  
Kazunari Nohara ◽  
Travis Nemkov ◽  
Angelo D’Alessandro ◽  
Seung-Hee Yoo ◽  
Zheng Chen
Keyword(s):  
Bile Acid ◽  
Cholesterol Metabolism ◽  
Orphan Receptor ◽  
Regulatory Function ◽  
Bile Acid Metabolism ◽  
16S Sequencing ◽  
Hepatic Expression ◽  
Cholesterol Levels ◽  
Age Related

Cholesterol and bile acid (BA) homeostasis plays a central role in systemic metabolism. Accumulating evidence suggests a key regulatory function of the circadian clock, our biological timer, in lipid metabolism, particularly cholesterol and bile acid flux. Previously, we showed that Nobiletin (NOB), a natural compound targeting the ROR (Retinoic acid receptor-related orphan receptor) nuclear receptors in the circadian oscillator, strongly protects lipid homeostasis, including normal serum cholesterol levels in high-fat (HF) fed mice at both young and old ages. In this study, we further examined the role of NOB in cholesterol metabolism in HF-fed aged mice, and found that NOB lowered the serum LDL/VLDL cholesterol levels and consequently the LDL/HDL ratio. BA levels in the serum were markedly reduced in the HF.NOB group, and examination of additional hepatic markers further indicate a protective role of NOB in the liver. At the molecular level, whereas HF feeding downregulated hepatic expression of several ROR target genes involved in bile acid synthesis, NOB treatment (HF.NOB) was able to rescue it. In accordance, fecal BA excretion was enhanced by NOB, and microbial 16S sequencing revealed alteration of several taxa known to be involved in secondary BA production in the gut. Together, these results demonstrate concerted effects of the clock-modulating compound NOB in cholesterol and BA metabolism, suggesting pharmacological manipulation of the clock as a novel therapeutic strategy against metabolic disorders and age-related decline.

Failure of adrenal corticosterone production in POMC-deficient mice results from lack of integrated effects of POMC peptides on multiple factors

2008 ◽  
Vol 295 (2) ◽  
pp. E446-E455 ◽  
Author(s):  
Jason Karpac ◽  
Katarzyna Czyzewska ◽  
Andras Kern ◽  
Richard S. Brush ◽  
Robert E. Anderson ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Scavenger Receptor ◽  
Type I ◽  
Protein Levels ◽  
Multiple Factors ◽  
Acth Treatment ◽  
Class B ◽  
Multistep Process ◽  
Adrenal Corticosterone ◽  
Selective Cholesterol Uptake

Production of corticosteroids from the adrenal gland is a multistep process in which corticosterone is enzymatically processed from its precursor cholesterol. The main hormone regulating the production of corticosterone is the proopiomelanocortin (POMC)-derived adrenocorticotropic hormone (ACTH). Adrenals of POMC-deficient (POMC−/−) mice do not produce corticosterone either at basal levels or in response to acute stimulation with ACTH. However, pharmacological amounts of ACTH delivered continuously elicit corticosterone production over time. To define the relative effects of ACTH on individual factors involved in corticosterone production, parameters of adrenal cholesterol metabolism and steroidogenesis were examined in POMC−/− mice compared with wild-type and ACTH-treated mutant mice. POMC−/− adrenals lack cholesterol esters (CE); adrenal CE is restored with ACTH treatment. However, discontinuation of ACTH treatment stops corticosterone production despite the presence of adrenal CE. Failure of corticosterone production by POMC−/− adrenals occurs despite the constitutive presence of transcripts of genes required for cholesterol metabolism and steroidogenesis. Levels of key proteins involved in selective cholesterol uptake and steroidogenesis were attenuated; ACTH treatment increased these protein levels, most significantly those of the receptor responsible for selective uptake of CE, scavenger receptor class B, type I (SR-BI). Our studies reveal that failure of corticosterone production of POMC−/− adrenal glands and its pharmacological reconstitution by ACTH are not mediated by any one individual protein, but rather as an integrated effect on multiple factors from import of the substrate cholesterol to its conversion to corticosterone.

scholarly journals Scavenger receptor class B type I regulates cellular cholesterol metabolism and cell signaling associated with breast cancer development

2013 ◽  
Vol 15 (5) ◽  
Author(s):  
Christiane Danilo ◽  
Jorge L Gutierrez-Pajares ◽  
Maria Antonietta Mainieri ◽  
Isabelle Mercier ◽  
Michael P Lisanti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Signaling ◽  
Cholesterol Metabolism ◽  
Scavenger Receptor ◽  
Cancer Development ◽  
Type I ◽  
Cellular Cholesterol ◽  
Breast Cancer Development ◽  
Scavenger Receptor Class ◽  
Class B

scholarly journals Regulation of Alternative Splicing of Liver Scavenger Receptor Class B Gene by Estrogen and the Involved Regulatory Splicing Factors

Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5295-5304 ◽  
Author(s):  
Xiaohui Zhang ◽  
Andrea N. Moor ◽  
Kathleen A. Merkler ◽  
Qiyuan Liu ◽  
Mark P. McLean
Keyword(s):  
Alternative Splicing ◽  
Scavenger Receptor ◽  
Splicing Factor ◽  
Splicing Factors ◽  
Type I ◽  
Hepatic Expression ◽  
Hepatic Cells ◽  
Scavenger Receptor Class ◽  
Class B ◽  
Alternative Splicing Factor

The scavenger receptor class B isoforms (SR-B) type I and type II mediate the selective uptake of high-density lipoprotein cholesterol and promote reverse cholesterol transport, an important atherosclerosis protection mechanism, in the liver. Previously it was shown that the hepatic expression of SR-BI and SR-BII is regulated by estrogen. In the present study, we demonstrate that estrogen differentially regulates expression of the glycosylated and nonglycosylated forms of SR-BI and SR-BII in rat liver and hepatic cells. We report that estrogen mainly induces the down-regulation of glycosylated SR-BI and the up-regulation of nonglycosylated SR-BII. To study how estrogen regulates expression of the SR-B isoforms, we constructed a SR-B minigene containing minimal genomic sequences and were able to demonstrate that estrogen directly regulates the pre-mRNA alternative splicing of the exogenously expressed SR-B minigene in hepatic cells. Furthermore, we showed that the overexpression of splicing factors alternative splicing factor/splicing factor 2, Transformer (Tra)-2α, and Tra2β changes the splicing pattern of SR-B dramatically, whereas other splicing factors, such as heterogeneous nuclear ribonucleoprotein-G, SC-35, and arginine/serine-rich p40, had no effect. We also demonstrate that estrogen regulates Tra2β expression levels in liver cells. These studies suggest that estrogen may regulate SR-B isoform expression at both the RNA splicing and posttranslational modification levels and that, for alternative splicing regulation, estrogen may function by regulating the expression of the splicing factors alternative splicing factor/splicing factor 2, Tra2α, and especially Tra2β.

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