Advances in Cholesterol and Lipid Metabolism

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Lipid Metabolism".

Deadline for manuscript submissions: closed (15 May 2022) | Viewed by 32351

Special Issue Editors


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Guest Editor
Department of Medicine, NYU Long Island School of Medicine, Mineola, New York, NY 11501, USA
Interests: acute coronary syndromes; cholesterol metabolism; cardiovascular; atherosclerosis
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Special Issue Information

Dear Colleagues,

Lipid metabolism plays a key role in the development of atherosclerotic cardiovascular disease (ASCVD) and is linked to pathological processes including obesity, diabetes and a number of neurologic disorders. In ASCVD, cholesterol, an essential cell membrane component, accumulates in the arterial wall. LDL is the main carrier of circulating cholesterol within the body and, when oxidatively modified, is highly atherogenic. Atheroprotective removal of cholesterol is predominantly via HDL-mediated reverse cholesterol transport. Approximately 40–65% of persons with Alzheimer’s disease carry the ApolipoproteinE-ε4 haplotype. In the last decade, our understanding of pathological mechanisms in disordered lipid metabolism has led to new biomarkers and drug treatments such as PCSK9 inhibitors for hypercholesterolemia. Recent progress in understanding biological pathways that influence lipid metabolism has implications in improving lifespan and quality of life for persons with ASCVD and other disorders.

For this Special Issue of Metabolites, we invite original research articles and reviews focused on developments in cholesterol and lipid metabolism highlighting how our evolving knowledge impacts treatment approaches to cardiovascular and neurologic disorders. We are particularly interested in the role of microRNAs, extracellular vesicles, complex signaling pathways and immune/inflammatory mechanisms in regulating lipid homeostasis in the cardiovascular and nervous systems.

Dr. Allison B Reiss
Dr. Joshua De Leon
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cholesterol
  • lipids
  • atherosclerosis
  • neurodegeneration
  • apolipoproteins
  • myocardial infarction
  • stroke
  • Alzheimer’s disease
  • microRNA
  • dyslipidemia

Published Papers (8 papers)

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Editorial

Jump to: Research, Review, Other

4 pages, 219 KiB  
Editorial
Special Issue on “Advances in Cholesterol and Lipid Metabolism”
by Allison B. Reiss and Joshua De Leon
Metabolites 2022, 12(8), 765; https://doi.org/10.3390/metabo12080765 - 19 Aug 2022
Cited by 1 | Viewed by 1505
Abstract
Cholesterol and lipid metabolism is a broad topic that encompasses multiple aspects of cellular function in every organ [...] Full article
(This article belongs to the Special Issue Advances in Cholesterol and Lipid Metabolism)

Research

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14 pages, 2077 KiB  
Article
Ubiquitous Aberration in Cholesterol Metabolism across Pancreatic Ductal Adenocarcinoma
by Venugopal Gunda, Thiago C. Genaro-Mattos, Jyoti B. Kaushal, Ramakanth Chirravuri-Venkata, Gopalakrishnan Natarajan, Kavita Mallya, Paul M. Grandgenett, Karoly Mirnics, Surinder K. Batra, Zeljka Korade and Satyanarayana Rachagani
Metabolites 2022, 12(1), 47; https://doi.org/10.3390/metabo12010047 - 07 Jan 2022
Cited by 6 | Viewed by 1929
Abstract
Pancreatic cancer (PC) is characterized by metabolic deregulations that often manifest as deviations in metabolite levels and aberrations in their corresponding metabolic genes across the clinical specimens and preclinical PC models. Cholesterol is one of the critical metabolites supporting PC, synthesized or acquired [...] Read more.
Pancreatic cancer (PC) is characterized by metabolic deregulations that often manifest as deviations in metabolite levels and aberrations in their corresponding metabolic genes across the clinical specimens and preclinical PC models. Cholesterol is one of the critical metabolites supporting PC, synthesized or acquired by PC cells. Nevertheless, the significance of the de novo cholesterol synthesis pathway has been controversial in PC, indicating the need to reassess this pathway in PC. We utilized preclinical models and clinical specimens of PC patients and cell lines and utilized mass spectrometry-based sterol analysis. Further, we also performed in silico analysis to corroborate the significance of de novo cholesterol synthesis pathway in PC. Our results demonstrated alteration in free sterol levels, including free cholesterol, across in vitro, in vivo, and clinical specimens of PC. Especially, our sterol analyses established consistent alterations in free cholesterol across the different PC models. Overall, this study demonstrates the significance and consistency in deviation of cholesterol synthesis pathway in PC while showing the aberrations in sterol metabolite intermediates and the related genes using preclinical models, in silico platforms, and the clinical specimens. Full article
(This article belongs to the Special Issue Advances in Cholesterol and Lipid Metabolism)
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11 pages, 306 KiB  
Article
A Matched Case-Control Study of Noncholesterol Sterols and Fatty Acids in Chronic Hemodialysis Patients
by Marek Vecka, Magdalena Dušejovská, Barbora Staňková, Ivan Rychlík and Aleš Žák
Metabolites 2021, 11(11), 774; https://doi.org/10.3390/metabo11110774 - 12 Nov 2021
Cited by 2 | Viewed by 1718
Abstract
Dyslipidemia is common among patients on hemodialysis, but its etiology is not fully understood. Although changes in cholesterol homeostasis and fatty acid metabolism play an important role during dialysis, the interaction of these metabolic pathways has yet to be studied in sufficient detail. [...] Read more.
Dyslipidemia is common among patients on hemodialysis, but its etiology is not fully understood. Although changes in cholesterol homeostasis and fatty acid metabolism play an important role during dialysis, the interaction of these metabolic pathways has yet to be studied in sufficient detail. In this study, we enrolled 26 patients on maintenance hemodialysis treatment (high-volume hemodiafiltration, HV HDF) without statin therapy (17 men/9 women) and an age/gender-matched group of 26 individuals without signs of nephropathy. The HV-HDF group exhibited more frequent signs of cardiovascular disease, disturbed saccharide metabolism, and altered lipoprotein profiles, manifesting in lower HDL-C, and raised concentrations of IDL-C and apoB-48 (all p < 0.01). HV-HDF patients had higher levels of campesterol (p < 0.01) and β-sitosterol (p = 0.06), both surrogate markers of cholesterol absorption and unchanged lathosterol concentrations. Fatty acid (FA) profiles were changed mostly in cholesteryl esters, with a higher content of saturated and n-3 polyunsaturated fatty acids (PUFA) in the HV-HDF group. However, n-6 PUFA in cholesteryl esters were less abundant (p < 0.001) in the HV-HDF group. Hemodialysis during end-stage kidney disease induces changes associated with higher absorption of cholesterol and disturbed lipoprotein metabolism. Changes in fatty acid metabolism reflect the combined effect of renal insufficiency and its comorbidities, mostly insulin resistance. Full article
(This article belongs to the Special Issue Advances in Cholesterol and Lipid Metabolism)
16 pages, 1562 KiB  
Article
Human Fecal Metabolome Reflects Differences in Body Mass Index, Physical Fitness, and Blood Lipoproteins in Healthy Older Adults
by Mengni Cui, Alessia Trimigno, Josue L. Castro-Mejía, Søren Reitelseder, Jacob Bülow, Rasmus Leidesdorff Bechshøft, Dennis Sandris Nielsen, Lars Holm, Søren Balling Engelsen and Bekzod Khakimov
Metabolites 2021, 11(11), 717; https://doi.org/10.3390/metabo11110717 - 21 Oct 2021
Cited by 7 | Viewed by 2719
Abstract
This study investigated how body mass index (BMI), physical fitness, and blood plasma lipoprotein levels are related to the fecal metabolome in older adults. The fecal metabolome data were acquired using proton nuclear magnetic resonance spectroscopy and gas chromatography–mass spectrometry on 163 healthy [...] Read more.
This study investigated how body mass index (BMI), physical fitness, and blood plasma lipoprotein levels are related to the fecal metabolome in older adults. The fecal metabolome data were acquired using proton nuclear magnetic resonance spectroscopy and gas chromatography–mass spectrometry on 163 healthy older adults (65–80 years old, 80 females and 83 males). Overweight and obese subjects (BMI ≥ 27) showed higher levels of fecal amino acids (AAs) (valine, alanine, and phenylalanine) compared to normal-weight subjects (BMI ≤ 23.5). Adults classified in the high-fitness group displayed slightly lower concentrations of fecal short-chain fatty acids, propionic acid, and AAs (methionine, leucine, glutamic acid, and threonine) compared to the low-fitness group. Subjects with lower levels of cholesterol in low-density lipoprotein particles (LDLchol, ≤2.6 mmol/L) displayed higher fecal levels of valine, glutamic acid, phenylalanine, and lactic acid, while subjects with a higher level of cholesterol in high-density lipoprotein particles (HDLchol, ≥2.1 mmol/L) showed lower fecal concentration of isovaleric acid. The results from this study suggest that the human fecal metabolome, which primarily represents undigested food waste and metabolites produced by the gut microbiome, carries important information about human health and should be closely integrated to other omics data for a better understanding of the role of the gut microbiome and diet on human health and metabolism. Full article
(This article belongs to the Special Issue Advances in Cholesterol and Lipid Metabolism)
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13 pages, 1669 KiB  
Article
Combined LXR and RXR Agonist Therapy Increases ABCA1 Protein Expression and Enhances ApoAI-Mediated Cholesterol Efflux in Cultured Endothelial Cells
by Kun Huang, Hanjoong Jo, Jing Echesabal-Chen and Alexis Stamatikos
Metabolites 2021, 11(9), 640; https://doi.org/10.3390/metabo11090640 - 18 Sep 2021
Cited by 12 | Viewed by 3130
Abstract
Endothelial ABCA1 expression protects against atherosclerosis and this atheroprotective effect is partially attributed to enhancing apoAI-mediated cholesterol efflux. ABCA1 is a target gene for LXR and RXR; therefore, treating endothelial cells with LXR and/or RXR agonists may increase ABCA1 expression. We tested whether [...] Read more.
Endothelial ABCA1 expression protects against atherosclerosis and this atheroprotective effect is partially attributed to enhancing apoAI-mediated cholesterol efflux. ABCA1 is a target gene for LXR and RXR; therefore, treating endothelial cells with LXR and/or RXR agonists may increase ABCA1 expression. We tested whether treating cultured immortalized mouse aortic endothelial cells (iMAEC) with the endogenous LXR agonist 22(R)-hydroxycholesterol, synthetic LXR agonist GW3965, endogenous RXR agonist 9-cis-retinoic acid, or synthetic RXR agonist SR11237 increases ABCA1 protein expression. We observed a significant increase in ABCA1 protein expression in iMAEC treated with either GW3965 or SR11237 alone, but no significant increase in ABCA1 protein was observed in iMAEC treated with either 22(R)-hydroxycholesterol or 9-cis-retionic acid alone. However, we observed significant increases in both ABCA1 protein expression and apoAI-mediated cholesterol efflux when iMAEC were treated with a combination of either 22(R)-hydroxycholesterol and 9-cis-retinoic acid or GW3965 and SR11237. Furthermore, treating iMAEC with either 22(R)-hydroxycholesterol and 9-cis-retinoic acid or GW3965 and SR11237 did not trigger an inflammatory response, based on VCAM-1, ICAM-1, CCL2, and IL-6 mRNA expression. Based on our findings, delivering LXR and RXR agonists precisely to endothelial cells may be a promising atheroprotective approach. Full article
(This article belongs to the Special Issue Advances in Cholesterol and Lipid Metabolism)
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Review

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22 pages, 1012 KiB  
Review
The Roles of Fatty Acids and Apolipoproteins in the Kidneys
by Xiaoyue Pan
Metabolites 2022, 12(5), 462; https://doi.org/10.3390/metabo12050462 - 20 May 2022
Cited by 6 | Viewed by 3544
Abstract
The kidneys are organs that require energy from the metabolism of fatty acids and glucose; several studies have shown that the kidneys are metabolically active tissues with an estimated energy requirement similar to that of the heart. The kidneys may regulate the normal [...] Read more.
The kidneys are organs that require energy from the metabolism of fatty acids and glucose; several studies have shown that the kidneys are metabolically active tissues with an estimated energy requirement similar to that of the heart. The kidneys may regulate the normal and pathological function of circulating lipids in the body, and their glomerular filtration barrier prevents large molecules or large lipoprotein particles from being filtered into pre-urine. Given the permeable nature of the kidneys, renal lipid metabolism plays an important role in affecting the rest of the body and the kidneys. Lipid metabolism in the kidneys is important because of the exchange of free fatty acids and apolipoproteins from the peripheral circulation. Apolipoproteins have important roles in the transport and metabolism of lipids within the glomeruli and renal tubules. Indeed, evidence indicates that apolipoproteins have multiple functions in regulating lipid import, transport, synthesis, storage, oxidation and export, and they are important for normal physiological function. Apolipoproteins are also risk factors for several renal diseases; for example, apolipoprotein L polymorphisms induce kidney diseases. Furthermore, renal apolipoprotein gene expression is substantially regulated under various physiological and disease conditions. This review is aimed at describing recent clinical and basic studies on the major roles and functions of apolipoproteins in the kidneys. Full article
(This article belongs to the Special Issue Advances in Cholesterol and Lipid Metabolism)
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26 pages, 1890 KiB  
Review
Apolipoprotein B and Cardiovascular Disease: Biomarker and Potential Therapeutic Target
by Jennifer Behbodikhah, Saba Ahmed, Ailin Elyasi, Lora J. Kasselman, Joshua De Leon, Amy D. Glass and Allison B. Reiss
Metabolites 2021, 11(10), 690; https://doi.org/10.3390/metabo11100690 - 08 Oct 2021
Cited by 90 | Viewed by 11947
Abstract
Apolipoprotein (apo) B, the critical structural protein of the atherogenic lipoproteins, has two major isoforms: apoB48 and apoB100. ApoB48 is found in chylomicrons and chylomicron remnants with one apoB48 molecule per chylomicron particle. Similarly, a single apoB100 molecule is contained per particle of [...] Read more.
Apolipoprotein (apo) B, the critical structural protein of the atherogenic lipoproteins, has two major isoforms: apoB48 and apoB100. ApoB48 is found in chylomicrons and chylomicron remnants with one apoB48 molecule per chylomicron particle. Similarly, a single apoB100 molecule is contained per particle of very-low-density lipoprotein (VLDL), intermediate density lipoprotein, LDL and lipoprotein(a). This unique one apoB per particle ratio makes plasma apoB concentration a direct measure of the number of circulating atherogenic lipoproteins. ApoB levels indicate the atherogenic particle concentration independent of the particle cholesterol content, which is variable. While LDL, the major cholesterol-carrying serum lipoprotein, is the primary therapeutic target for management and prevention of atherosclerotic cardiovascular disease, there is strong evidence that apoB is a more accurate indicator of cardiovascular risk than either total cholesterol or LDL cholesterol. This review examines multiple aspects of apoB structure and function, with a focus on the controversy over use of apoB as a therapeutic target in clinical practice. Ongoing coronary artery disease residual risk, despite lipid-lowering treatment, has left patients and clinicians with unsatisfactory options for monitoring cardiovascular health. At the present time, the substitution of apoB for LDL-C in cardiovascular disease prevention guidelines has been deemed unjustified, but discussions continue. Full article
(This article belongs to the Special Issue Advances in Cholesterol and Lipid Metabolism)
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Other

8 pages, 575 KiB  
Perspective
The Role of Fructose as a Cardiovascular Risk Factor: An Update
by Stefan-Sebastian Busnatu, Teodor Salmen, Maria-Alexandra Pana, Manfredi Rizzo, Tiziana Stallone, Nikolaos Papanas, Djordje Popovic, Denisa Tanasescu, Dragos Serban and Anca Pantea Stoian
Metabolites 2022, 12(1), 67; https://doi.org/10.3390/metabo12010067 - 12 Jan 2022
Cited by 26 | Viewed by 3947
Abstract
There is increasing presence of fructose in food and drinks, and some evidence suggests that its higher consumption increases cardiovascular risk, although the mechanisms still remain not fully elucidated. Cardiovascular diseases (CVD) are still responsible for one-third of deaths worldwide, and therefore, their [...] Read more.
There is increasing presence of fructose in food and drinks, and some evidence suggests that its higher consumption increases cardiovascular risk, although the mechanisms still remain not fully elucidated. Cardiovascular diseases (CVD) are still responsible for one-third of deaths worldwide, and therefore, their prevention should be assessed and managed comprehensively and not by the evaluation of individual risk factor components. Lifestyle risk factors for CVD include low degree of physical activity, high body mass index, alcohol consumption, smoking, and nutritional factors. Indeed, nutritional risk factors for CVD include unhealthy dietary behaviors, such as high intake of refined foods, unhealthy fats, added sugars, and sodium and a low intake of fruits, vegetables, whole grains, fiber, fish, and nuts. Even though there is no definitive association between CVD incidence and high consumption of total sugar, such as sucrose and fructose, there is, however, evidence that total sugars, added sugars, and fructose are harmfully associated with CVD mortality. Since high fructose intake is associated with elevated plasma triglyceride levels, as well as insulin resistance, diabetes hyperuricemia, and non-alcoholic fatty liver disease, further longitudinal studies should be conducted to fully elucidate the potential association between certain sugars and CVD. Full article
(This article belongs to the Special Issue Advances in Cholesterol and Lipid Metabolism)
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