Cholesterol metabolism: a new molecular switch to control inflammation DOI Creative Commons
Diana Cardoso, Esperanza Perucha

Clinical Science, Journal Year: 2021, Volume and Issue: 135(11), P. 1389 - 1408

Published: June 1, 2021

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

Language: Английский

Gut Microbiota and Cardiovascular Disease DOI Open Access
Marco Witkowski,

Taylor L. Weeks,

Stanley L. Hazen

et al.

Circulation Research, Journal Year: 2020, Volume and Issue: 127(4), P. 553 - 570

Published: July 30, 2020

Fecal microbial community changes are associated with numerous disease states, including cardiovascular (CVD). However, such data merely associative. A causal contribution for gut microbiota in CVD has been further supported by a multitude of more direct experimental evidence. Indeed, transplantation studies, specific microbiota-dependent pathways, and downstream metabolites have all shown to influence host metabolism CVD, sometimes through identified receptors. Multiple metaorganismal pathways (involving both microbe host) impact animal models show striking clinical associations human studies. For example, trimethylamine N-oxide and, recently, phenylacetylglutamine whose blood levels incident risks large-scale Importantly, link these other metabolites/pathways mechanistic model Phenylacetylglutamine, was recently promote adverse phenotypes the via interaction multiple ARs (adrenergic receptors)-a class key receptors that regulate homeostasis. In this review, we summarize recent advances microbiome research related cardiometabolic helped move field forward from associative causative results. We focus on compounds/pathways, attention paid short-chain fatty acids, secondary bile N-oxide, phenylacetylglutamine. also discuss novel therapeutic strategies directly targeting improve outcomes.

Language: Английский

Citations

717
Cholesterol metabolism in cancer: mechanisms and therapeutic opportunities DOI

Binlu Huang,

Bao‐Liang Song, Chenqi Xu

et al.

Nature Metabolism, Journal Year: 2020, Volume and Issue: 2(2), P. 132 - 141

Published: Feb. 10, 2020

Language: Английский

Citations

633
Metabolic signaling in T cells DOI Creative Commons
Justin A. Shyer, Richard A. Flavell, Will Bailis

et al.

Cell Research, Journal Year: 2020, Volume and Issue: 30(8), P. 649 - 659

Published: July 24, 2020

Abstract The maintenance of organismal homeostasis requires partitioning and transport biochemical molecules between organ systems, their composite cells, subcellular organelles. Although transcriptional programming undeniably defines the functional state cells tissues, underlying networks are intricately intertwined with transcriptional, translational, post-translational regulation. Studies metabolic regulation immunity have elegantly illustrated this phenomenon. immune system interface a diverse set environmental conditions. Circulating perfuse peripheral organs in blood lymph, patrolling for pathogen invasion. Resident remain tissues play more newly appreciated roles tissue immunity. Each these cell populations interacts unique dynamic environments, which vary greatly composition. Furthermore, effector response to activating cues cellular adaptations supply requisite landscape. In review, we examine role spatial processes function. We focus on studies lymphocyte metabolism, reference greater immunometabolism literature when appropriate illustrate concept.

Language: Английский

Citations

262
Citrobacter rodentium–host–microbiota interactions: immunity, bioenergetics and metabolism DOI
Caroline Mullineaux-Sanders, Julia Sanchez‐Garrido,

Eve G. D. Hopkins

et al.

Nature Reviews Microbiology, Journal Year: 2019, Volume and Issue: 17(11), P. 701 - 715

Published: Sept. 20, 2019

Language: Английский

Citations

148
Enterically derived high-density lipoprotein restrains liver injury through the portal vein DOI
Yong‐Hyun Han, Emily J. Onufer,

Li‐Hao Huang

et al.

Science, Journal Year: 2021, Volume and Issue: 373(6553)

Published: July 22, 2021

Intestinal HDL is hepatoprotective High-density lipoprotein (HDL) important for cholesterol metabolism and may have anti-inflammatory antimicrobial properties. Although mainly produced by the liver, intestine also a source. Han et al. show in mice that intestinal not routed to systemic circulation. Rather, form of HDL3, it directly transported liver through hepatic portal vein. There, sequesters bacterial lipopolysaccharide from gut can trigger inflammation damage. In various models injury, loss enteric exacerbated pathology. By contrast, drugs elevating improved disease outcomes. HDL3 enriched human venous blood, suggesting be targetable treatment disease. Science , abe6729, this issue p. eabe6729

Language: Английский

Citations

145
The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease DOI Open Access
Leonor Jacobo‐Albavera, Mayra Domínguez‐Pérez, Diana Jhoseline Medina-Leyte

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(4), P. 1593 - 1593

Published: Feb. 5, 2021

Cholesterol homeostasis is essential in normal physiology of all cells. One several proteins involved cholesterol the ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein widely expressed many tissues. its main functions efflux intracellular free and phospholipids across plasma membrane to combine with apolipoproteins, mainly apolipoprotein A-I (Apo A-I), forming nascent high-density lipoprotein-cholesterol (HDL-C) particles, first step reverse transport (RCT). In addition, ABCA1 regulates phospholipid content affecting lipid rafts, microparticle (MP) formation cell signaling. Thus, it not surprising that impaired function altered may affect different organs pathophysiology broad array diseases. This review describes evidence obtained from animal models, human studies genetic variation explaining how dyslipidemia, coronary heart disease (CHD), type 2 diabetes (T2D), thrombosis, neurological disorders, age-related macular degeneration (AMD), glaucoma, viral infections cancer progression.

Language: Английский

Citations

119
Influence of cholesterol on cancer progression and therapy DOI Creative Commons
Shyamananda Singh Mayengbam, Abhijeet Singh, Ajay D. Pillai

et al.

Translational Oncology, Journal Year: 2021, Volume and Issue: 14(6), P. 101043 - 101043

Published: March 21, 2021

Cholesterol is a fundamental molecule necessary for the maintenance of cell structure and vital to various normal biological functions. It key factor in lifestyle-related diseases including obesity, diabetes, cardiovascular disease, cancer. Owing its altered serum chemistry status under pathological states, it now being investigated unravel mechanism by which triggers health complications. Numerous clinical studies cancer patients indicate an alteration blood cholesterol level (either decreased or increased) comparison healthy individuals. This article elaborates on our understanding as how hijacked malignancy development, survival, stemness, progression, metastasis cancerous cells. Also, provides glimpse derived entities, alters signaling pathway towards their advantage. Moreover, deregulation metabolism has been often reported hamper treatment strategies different In this context, attempts have made bring forth relevance targeted, pre-clinical modalities. Thus, role deciphering associated molecular mechanisms progression therapy are improvement management cancers.

Language: Английский

Citations

113
SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection DOI Open Access
Θεόδωρος Ανδρουτσάκος, Narjes Nasiri‐Ansari, Athanasios‐Dimitrios Bakasis

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(6), P. 3107 - 3107

Published: March 13, 2022

Non-alcoholic fatty liver disease (NAFLD) is an 'umbrella' term, comprising a spectrum ranging from benign, steatosis to non-alcoholic steatohepatitis, fibrosis and eventually cirrhosis hepatocellular carcinoma. NAFLD has evolved as major health problem in recent years. Discovering ways prevent or delay the progression of become global focus. Lifestyle modifications remain cornerstone treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) emerging promising agents. Processes regulated by SGLT-2i, such endoplasmic reticulum (ER) oxidative stress, low-grade inflammation, autophagy apoptosis all implicated pathogenesis. In this review, we summarize current understanding pathophysiology, specifically focus on potential impact SGLT-2i development progression, providing evidence vitro, animal human studies. Given evidence, further mechanistic studies would advance our exact mechanisms underlying pathogenesis beneficial actions context treatment.

Language: Английский

Citations

98
Inhibition of ASGR1 decreases lipid levels by promoting cholesterol excretion DOI

Ju-Qiong Wang,

Liang-Liang Li, Ao Hu

et al.

Nature, Journal Year: 2022, Volume and Issue: 608(7922), P. 413 - 420

Published: Aug. 3, 2022

Language: Английский

Citations

98
Functional significance of cholesterol metabolism in cancer: from threat to treatment DOI Creative Commons

Mingming Xiao,

Jin Xu, Wei Wang

et al.

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(9), P. 1982 - 1995

Published: Sept. 1, 2023

Abstract Cholesterol is an essential structural component of membranes that contributes to membrane integrity and fluidity. homeostasis plays a critical role in the maintenance cellular activities. Recently, increasing evidence has indicated cholesterol major determinant by modulating cell signaling events governing hallmarks cancer. Numerous studies have shown functional significance metabolism tumorigenesis, cancer progression metastasis through its regulatory effects on immune response, ferroptosis, autophagy, stemness, DNA damage response. Here, we summarize recent literature describing cells, including pathways mutual mechanisms involved metabolism. We also discuss various drugs targeting suggest new strategies for treatment.

Language: Английский

Citations

75