scholarly journals Contemporary aspects of cholesterol metabolism in cattle.

2021 ◽  
pp. 91-105
Author(s):  
O. I. Sebezhko ◽  
K. N. Narozhnykh ◽  
O. S. Korotkevich ◽  
D. A. Alexandrova ◽  
I. N. Morozov
Keyword(s):  
Cholesterol Metabolism ◽  
Phenotypic Variability ◽  
Cholesterol Biosynthesis ◽  
Molecular Genetic ◽  
Deficiency Syndrome ◽  
The Body ◽  
Cholesterol Homeostasis ◽  
High Density Lipoproteins ◽  
Nucleotide Polymorphisms ◽  
Endogenous Synthesis

The literature review presents the current understanding of cholesterol metabolism occurring under physiological conditions. The homeostasis of cholesterol in the body is determined by its endogenous synthesis, the transition to the cell from plasma as part of low-densitylipoproteins( LDL), the release of their cells as part of high-density lipoproteins (HDL). The molecular-genetic mechanisms of regulation of cholesterol homeostasis are described in detail. The genes for cholesterol biosynthesis in major multicellular animals were inherited from their last common eukaryotic ancestor and are evolutionarily conserved for cholesterol biosynthesis. Non-coding variants of singlenucleotide polymorphisms can significantly contribute to the phenotypic variability of cholesterol, and missense variants that lead to the replacement of amino acids in proteins can have a significant effect on the phenotypic variability. The modern aspects of cholesterol homeostasis in cattle are formed and sufficiently fully presented. During absence of exogenous intake, the balance of cholesterol in cattle is maintained by endogenous synthesis, occurring mainly in the liver, the intake of lipoproteins, as well as reverse transport mechanisms. This review gives an idea that the stability of homeostasis can be achieved only with the complex interaction of all systems (transport, enzyme, receptor) involved in this process. The analysis of the latest scientific works concerning the problem of the content and regulation of cholesterol in cow’s milk is presented. Significant single-nucleotide polymorphisms localized in the ACAT2, LDLR, DGAT, and AGPAT1 genes involved in the exchange of cholesterol in the liver or its transport and associated with the level of cholesterol in milk are described. Part of the review is devoted to cholesterol deficiency syndrome in Holstein cattle (HCD). Modern data on the prevalence, molecular and genetic basis, clinical and laboratory manifestations of the syndrome are presented.

scholarly journals Mathematical Models for Cholesterol Metabolism and Transport

Processes ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 155
Author(s):  
Fangyuan Zhang ◽  
Brittany Macshane ◽  
Ryan Searcy ◽  
Zuyi Huang
Keyword(s):  
Mathematical Models ◽  
Drug Targets ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
The Body ◽  
Cholesterol Homeostasis ◽  
Whole Body ◽  
Entire Body ◽  
High Cholesterol ◽  
Cholesterol Levels

Cholesterol is an essential component of eukaryotic cellular membranes. It is also an important precursor for making other molecules needed by the body. Cholesterol homeostasis plays an essential role in human health. Having high cholesterol can increase the chances of getting heart disease. As a result of the risks associated with high cholesterol, it is imperative that studies are conducted to determine the best course of action to reduce whole body cholesterol levels. Mathematical models can provide direction on this. By examining existing models, the suitable reactions or processes for drug targeting to lower whole-body cholesterol can be determined. This paper examines existing models in the literature that, in total, cover most of the processes involving cholesterol metabolism and transport, including: the absorption of cholesterol in the intestine; the cholesterol biosynthesis in the liver; the storage and transport of cholesterol between the intestine, the liver, blood vessels, and peripheral cells. The findings presented in these models will be discussed for potential combination to form a comprehensive model of cholesterol within the entire body, which is then taken as an in-silico patient for identifying drug targets, screening drugs, and designing intervention strategies to regulate cholesterol levels in the human body.

scholarly journals Abnormal brain cholesterol homeostasis in Alzheimer’s disease—a targeted metabolomic and transcriptomic study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Vijay R. Varma ◽  
H. Büşra Lüleci ◽  
Anup M. Oommen ◽  
Sudhir Varma ◽  
Chad T. Blackshear ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Tissue ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Cholesterol Homeostasis ◽  
Transcriptomic Data ◽  
Brain Cholesterol ◽  
Cholesterol Levels

AbstractThe role of brain cholesterol metabolism in Alzheimer’s disease (AD) remains unclear. Peripheral and brain cholesterol levels are largely independent due to the impermeability of the blood brain barrier (BBB), highlighting the importance of studying the role of brain cholesterol homeostasis in AD. We first tested whether metabolite markers of brain cholesterol biosynthesis and catabolism were altered in AD and associated with AD pathology using linear mixed-effects models in two brain autopsy samples from the Baltimore Longitudinal Study of Aging (BLSA) and the Religious Orders Study (ROS). We next tested whether genetic regulators of brain cholesterol biosynthesis and catabolism were altered in AD using the ANOVA test in publicly available brain tissue transcriptomic datasets. Finally, using regional brain transcriptomic data, we performed genome-scale metabolic network modeling to assess alterations in cholesterol biosynthesis and catabolism reactions in AD. We show that AD is associated with pervasive abnormalities in cholesterol biosynthesis and catabolism. Using transcriptomic data from Parkinson’s disease (PD) brain tissue samples, we found that gene expression alterations identified in AD were not observed in PD, suggesting that these changes may be specific to AD. Our results suggest that reduced de novo cholesterol biosynthesis may occur in response to impaired enzymatic cholesterol catabolism and efflux to maintain brain cholesterol levels in AD. This is accompanied by the accumulation of nonenzymatically generated cytotoxic oxysterols. Our results set the stage for experimental studies to address whether abnormalities in cholesterol metabolism are plausible therapeutic targets in AD.

scholarly journals SUN-751 RORγ Is a Master Regulator of Tumor Lipid Metabolism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Hong-Wu Chen
Keyword(s):  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Cholesterol Homeostasis ◽  
Synthesis Rate ◽  
Host Animal ◽  
Master Regulator ◽  
Genome Wide ◽  
Histone H3k27 ◽  
Lowering Drug ◽  
Potent Tumor

Abstract Lipid and cholesterol metabolism reprogramming is strongly linked to tumorigenesis and therapeutic resistance. Our recent genetic disruptions via CRISPR KO and gene silencing and pharmacological inhibition clearly demonstrated that nuclear receptor RORγ plays a crucial role in control of lipid and cholesterol biosynthesis gene programs specifically in certain types and subtypes of cancer cells and tumors. Indeed, its antagonists display potent tumor inhibitions in patient-derived xenografts (PDX) and in immune-intact tumor models. Interestingly, RORγ inhibition resulted in decreased cholesterol synthesis rate specifically in tumors without significant impact to the host animal cholesterol homeostasis. Our ChIP-seq demonstrated that in a subtype of breast cancer RORγ cistrome is largely overlapping with that of SREBP2, a well-established master regulator of lipid and cholesterol biosynthesis. Our further analyses found that RORγ functions dominantly over that of SREBP2 via its association with SREBP2 and facilitation of its genome-wide recruitment and histone H3K27 acetylation. Inhibition of RORγ completely negates the negative feedback activation of the cholesterol program induced by cholesterol-lowering drug statins and mediated by SREBP2. Treatment of animals with the antagonists in combination with statins showed a highly synergistic anti-tumor effects. Together, our study uncovers RORγ as a novel master regulator of lipid and cholesterol metabolism operating selectively in subtypes of cancer.

Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

2017 ◽  
Vol 55 (3) ◽  
Author(s):  
Tamara Gojkovic ◽  
Sandra Vladimirov ◽  
Vesna Spasojevic-Kalimanovska ◽  
Aleksandra Zeljkovic ◽  
Jelena Vekic ◽  
...  
Keyword(s):  
Cholesterol Synthesis ◽  
Cholesterol Metabolism ◽  
Relative Proportion ◽  
Therapy Response ◽  
Cholesterol Absorption ◽  
Cholesterol Homeostasis ◽  
High Density Lipoproteins ◽  
Treatment Optimization ◽  
Lipoprotein Subclasses ◽  
Atherosclerosis Progression

AbstractBackground:Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization.Methods:The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis.Results:In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05).Conclusions:The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

scholarly journals Impact of Cholesterol Metabolism in Immune Cell Function and Atherosclerosis

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2021 ◽  
Author(s):  
María Aguilar-Ballester ◽  
Andrea Herrero-Cervera ◽  
Ángela Vinué ◽  
Sergio Martínez-Hervás ◽  
Herminia González-Navarro
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
De Novo ◽  
Cholesterol Metabolism ◽  
The Body ◽  
Cholesterol Homeostasis ◽  
Hematopoietic Stem ◽  
Regulatory Pathways ◽  
Cholesterol Levels ◽  
Atherosclerosis Development

Cholesterol, the most important sterol in mammals, helps maintain plasma membrane fluidity and is a precursor of bile acids, oxysterols, and steroid hormones. Cholesterol in the body is obtained from the diet or can be de novo synthetized. Cholesterol homeostasis is mainly regulated by the liver, where cholesterol is packed in lipoproteins for transport through a tightly regulated process. Changes in circulating lipoprotein cholesterol levels lead to atherosclerosis development, which is initiated by an accumulation of modified lipoproteins in the subendothelial space; this induces significant changes in immune cell differentiation and function. Beyond lesions, cholesterol levels also play important roles in immune cells such as monocyte priming, neutrophil activation, hematopoietic stem cell mobilization, and enhanced T cell production. In addition, changes in cholesterol intracellular metabolic enzymes or transporters in immune cells affect their signaling and phenotype differentiation, which can impact on atherosclerosis development. In this review, we describe the main regulatory pathways and mechanisms of cholesterol metabolism and how these affect immune cell generation, proliferation, activation, and signaling in the context of atherosclerosis.

scholarly journals Genetic deletion of Abcc6 disturbs cholesterol homeostasis in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bettina Ibold ◽  
Janina Tiemann ◽  
Isabel Faust ◽  
Uta Ceglarek ◽  
Julia Dittrich ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Pseudoxanthoma Elasticum ◽  
Serum Levels ◽  
Cholesterol Homeostasis ◽  
Cholesterol Depletion ◽  
Transferase Activity

AbstractGenetic studies link adenosine triphosphate-binding cassette transporter C6 (ABCC6) mutations to pseudoxanthoma elasticum (PXE). ABCC6 sequence variations are correlated with altered HDL cholesterol levels and an elevated risk of coronary artery diseases. However, the role of ABCC6 in cholesterol homeostasis is not widely known. Here, we report reduced serum cholesterol and phytosterol levels in Abcc6-deficient mice, indicating an impaired sterol absorption. Ratios of cholesterol precursors to cholesterol were increased, confirmed by upregulation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr) expression, suggesting activation of cholesterol biosynthesis in Abcc6−/− mice. We found that cholesterol depletion was accompanied by a substantial decrease in HDL cholesterol mediated by lowered ApoA-I and ApoA-II protein levels and not by inhibited lecithin-cholesterol transferase activity. Additionally, higher proprotein convertase subtilisin/kexin type 9 (Pcsk9) serum levels in Abcc6−/− mice and PXE patients and elevated ApoB level in knockout mice were observed, suggesting a potentially altered very low-density lipoprotein synthesis. Our results underline the role of Abcc6 in cholesterol homeostasis and indicate impaired cholesterol metabolism as an important pathomechanism involved in PXE manifestation.

scholarly journals TDP-43 mediates SREBF2-regulated gene expression required for oligodendrocyte myelination

2021 ◽  
Vol 220 (9) ◽  
Author(s):  
Wan Yun Ho ◽  
Jer-Cherng Chang ◽  
Kenneth Lim ◽  
Amaury Cazenave-Gassiot ◽  
Aivi T. Nguyen ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Cholesterol Homeostasis ◽  
Cholesterol Levels ◽  
The Central Nervous System ◽  
Cholesterol Supplementation ◽  
Regulated Gene Expression ◽  
Lateral Sclerosis

Cholesterol metabolism operates autonomously within the central nervous system (CNS), where the majority of cholesterol resides in myelin. We demonstrate that TDP-43, the pathological signature protein for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), influences cholesterol metabolism in oligodendrocytes. TDP-43 binds directly to mRNA of SREBF2, the master transcription regulator for cholesterol metabolism, and multiple mRNAs encoding proteins responsible for cholesterol biosynthesis and uptake, including HMGCR, HMGCS1, and LDLR. TDP-43 depletion leads to reduced SREBF2 and LDLR expression, and cholesterol levels in vitro and in vivo. TDP-43–mediated changes in cholesterol levels can be restored by reintroducing SREBF2 or LDLR. Additionally, cholesterol supplementation rescues demyelination caused by TDP-43 deletion. Furthermore, oligodendrocytes harboring TDP-43 pathology from FTD patients show reduced HMGCR and HMGCS1, and coaggregation of LDLR and TDP-43. Collectively, our results indicate that TDP-43 plays a role in cholesterol homeostasis in oligodendrocytes, and cholesterol dysmetabolism may be implicated in TDP-43 proteinopathies–related diseases.

scholarly journals Cholesterol metabolism: a new molecular switch to control inflammation

2021 ◽  
Vol 135 (11) ◽  
pp. 1389-1408
Author(s):  
Diana Cardoso ◽  
Esperanza Perucha
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Cholesterol Metabolism ◽  
The Body ◽  
Cholesterol Homeostasis ◽  
Metabolic Reprogramming ◽  
Human Diseases ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Effector Response

Abstract The immune system protects the body against harm by inducing inflammation. During the immune response, cells of the immune system get activated, divided and differentiated in order to eliminate the danger signal. This process relies on the metabolic reprogramming of both catabolic and anabolic pathways not only to produce energy in the form of ATP but also to generate metabolites that exert key functions in controlling the response. Equally important to mounting an appropriate effector response is the process of immune resolution, as uncontrolled inflammation is implicated in the pathogenesis of many human diseases, including allergy, chronic inflammation and cancer. In this review, we aim to introduce the reader to the field of cholesterol immunometabolism and discuss how both metabolites arising from the pathway and cholesterol homeostasis are able to impact innate and adaptive immune cells, staging cholesterol homeostasis at the centre of an adequate immune response. We also review evidence that demonstrates the clear impact that cholesterol metabolism has in both the induction and the resolution of the inflammatory response. Finally, we propose that emerging data in this field not only increase our understanding of immunometabolism but also provide new tools for monitoring and intervening in human diseases, where controlling and/or modifying inflammation is desirable.

scholarly journals Polyphenol-Rich Black Elderberry Extract Stimulates Transintestinal Cholesterol Excretion

2021 ◽  
Vol 11 (6) ◽  
pp. 2790
Author(s):  
Sohyeon Jeon ◽  
Minji Kim ◽  
Bohkyung Kim
Keyword(s):  
Messenger Rna ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Mrna Levels ◽  
Expression Of Genes ◽  
Apical Side ◽  
Cholesterol Excretion ◽  
Stimulation Of

Hypercholesterolemia is the primary risk factor for cardiovascular disease (CVD). Recent studies reported that the stimulation of transintestinal cholesterol excretion (TICE), a nonbiliary cholesterol excretion, can be a strategy for preventing CVD. Black elderberry (Sambucus nigra) has been reported to reduce the risk of CVD via its antioxidant, anti-inflammatory, and hypocholesterolemic effects. However, little is known about the role of black elderberry in intestinal cholesterol metabolism despite its well-known effects on cholesterol homeostasis regulation. To investigate the effects of polyphenol-rich black elderberry extract (BEE) on intestinal cholesterol metabolism, we measured the expression of genes involved in cholesterol biosynthesis and flux in Caco-2 cells. BEE significantly decreased the messenger RNA (mRNA) and protein levels of genes for cholesterol absorption, such as Niemann–Pick C1 Like 1 and ATP-binding cassette transporter A1 (ABCA1). In contrast, there was marked induction of low-density lipoprotein receptor, ABCG5/G8, and ABCB1 in BEE-treated Caco-2 cells. Furthermore, BEE decreased the expression of genes for lipogenesis and altered the mRNA levels of sirtuins. All of the genes altered by BEE were in the direction of flux cholesterol from the basolateral to apical side of enterocytes, indicating stimulation of TICE. These results support the hypocholesterolemic effects of BEE for the prevention of CVD.

scholarly journals Balancing cholesterol in the brain: from synthesis to disposal

2022 ◽  
pp. 1-27
Author(s):  
Lydia Qian ◽  
Amanda B. Chai ◽  
Ingrid C. Gelissen ◽  
Andrew J. Brown
Keyword(s):  
De Novo ◽  
Cholesterol Metabolism ◽  
Peripheral Circulation ◽  
The Body ◽  
Cholesterol Homeostasis ◽  
Myelin Sheaths ◽  
The Central Nervous System ◽  
Vital Component ◽  
The Brain ◽  
Limited Exchange

The cholesterol is a vital component of cell membranes and myelin sheaths, and a precursor for essential molecules such as steroid hormones. In humans, cholesterol is partially obtained through the diet, while the majority is synthesized in the body, primarily in the liver. However, the limited exchange between the central nervous system and peripheral circulation, due to the presence of the blood-brain barrier, necessitates cholesterol in the brain to be exclusively acquired from local de novo synthesis. This cholesterol is reutilized efficiently, rendering a much slower overall turnover of the compound in the brain as compared with the periphery. Furthermore, brain cholesterol is regulated independently from peripheral cholesterol. Numerous enzymes, proteins, and other factors are involved in cholesterol synthesis and metabolism in the brain. Understanding the unique mechanisms and pathways involved in the maintenance of cholesterol homeostasis in the brain is critical, considering perturbations to these processes are implicated in numerous neurodegenerative diseases. This review focuses on the developing understanding of cholesterol metabolism in the brain, discussing the sites and processes involved in its synthesis and regulation, as well as the mechanisms involved in its distribution throughout, and elimination from, the brain.

Sign in / Sign up

Export Citation Format

Share Document