Special Issue "Lipid Metabolism"

Quicklinks

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: closed (30 September 2014)

Special Issue Editor

Guest Editor
Prof. Dr. Annette Graham (Website)

Life Sciences, School of Health and Life Sciences, and the Institute for Applied Health Research, Glasgow Caledonian University, Glasgow, UK
Phone: 0141 331 3722
Interests: Intracellular lipid transport in health and disease; lipid and lipoprotein metabolism; vascular contributions to diabetes and Alzheimer’s disease

Special Issue Information

Dear Colleagues,

It is becoming increasingly evident that intracellular proteins can specifically regulate the direction of lipid transport within cells, thereby influencing the storage, synthesis and export of lipids, and the activity of nuclear receptor transcription factors involved in lipid and lipoprotein metabolism. Defective intracellular lipid transport may also contribute to a number of disease states, including metabolic disorders and tumorigenesis.
For this special issue, we invite research articles on aspects of lipid transport within cells and tissues, and particularly those which contribute to our understanding of the role of intracellular lipid transporters in pathological conditions.

Prof. Annette Graham
Guest Editor

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed Open Access quarterly 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 600 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Published Papers (12 papers)

View options order results:
result details:
Displaying articles 1-12
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Effect of Different Omega-6/Omega-3 Polyunsaturated Fatty Acid Ratios on the Formation of Monohydroxylated Fatty Acids in THP-1 Derived Macrophages
Biology 2015, 4(2), 314-326; doi:10.3390/biology4020314
Received: 30 October 2014 / Revised: 28 February 2015 / Accepted: 10 March 2015 / Published: 9 April 2015
PDF Full-text (121 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Omega-6 and omega-3 polyunsaturated fatty acids (n-6 and n-3 PUFA) can modulate inflammatory processes. In western diets, the content of n-6 PUFA is much higher than that of n-3 PUFA, which has been suggested to promote a pro-inflammatory phenotype. The aim of [...] Read more.
Omega-6 and omega-3 polyunsaturated fatty acids (n-6 and n-3 PUFA) can modulate inflammatory processes. In western diets, the content of n-6 PUFA is much higher than that of n-3 PUFA, which has been suggested to promote a pro-inflammatory phenotype. The aim of this study was to analyze the effect of modulating the n-6/n-3 PUFA ratio on the formation of monohydroxylated fatty acid (HO-FAs) derived from the n-6 PUFA arachidonic acid (AA) and the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in THP-1 macrophages by means of LC-MS. Lipid metabolites were measured in THP-1 macrophage cell pellets. The concentration of AA-derived hydroxyeicosatetraenoic acids (HETEs) was not significantly changed when incubated THP-1 macrophages in a high AA/(EPA+DHA) ratio of 19/1 vs. a low ratio AA/(EPA+DHA) of 1/1 (950.6 ± 110 ng/mg vs. 648.2 ± 92.4 ng/mg, p = 0.103). Correspondingly, the concentration of EPA-derived hydroxyeicosapentaenoic acids (HEPEs) and DHA-derived hydroxydocosahexaenoic acids (HDHAs) were significantly increased (63.9 ± 7.8 ng/mg vs. 434.4 ± 84.3 ng/mg, p = 0.012 and 84.9 ± 18.3 ng/mg vs. 439.4 ± 82.7 ng/mg, p = 0.014, respectively). Most notable was the strong increase of 18-hydroxyeicosapentaenoic acid (18-HEPE) formation in THP-1 macrophages, with levels of 170.9 ± 40.2 ng/mg protein in the high n-3 PUFA treated cells. Thus our data indicate that THP-1 macrophages prominently utilize EPA and DHA for monohydroxylated metabolite formation, in particular 18-HEPE, which has been shown to be released by macrophages to prevent pressure overload-induced maladaptive cardiac remodeling. Full article
(This article belongs to the Special Issue Lipid Metabolism)
Open AccessArticle MALDI Mass Spectrometry Imaging of Lipids and Gene Expression Reveals Differences in Fatty Acid Metabolism between Follicular Compartments in Porcine Ovaries
Biology 2015, 4(1), 216-236; doi:10.3390/biology4010216
Received: 25 September 2014 / Revised: 18 February 2015 / Accepted: 27 February 2015 / Published: 6 March 2015
Cited by 2 | PDF Full-text (1654 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In mammals, oocytes develop inside the ovarian follicles; this process is strongly supported by the surrounding follicular environment consisting of cumulus, granulosa and theca cells, and follicular fluid. In the antral follicle, the final stages of oogenesis require large amounts of energy [...] Read more.
In mammals, oocytes develop inside the ovarian follicles; this process is strongly supported by the surrounding follicular environment consisting of cumulus, granulosa and theca cells, and follicular fluid. In the antral follicle, the final stages of oogenesis require large amounts of energy that is produced by follicular cells from substrates including glucose, amino acids and fatty acids (FAs). Since lipid metabolism plays an important role in acquiring oocyte developmental competence, the aim of this study was to investigate site-specificity of lipid metabolism in ovaries by comparing lipid profiles and expression of FA metabolism-related genes in different ovarian compartments. Using MALDI Mass Spectrometry Imaging, images of porcine ovary sections were reconstructed from lipid ion signals for the first time. Cluster analysis of ion spectra revealed differences in spatial distribution of lipid species among ovarian compartments, notably between the follicles and interstitial tissue. Inside the follicles analysis differentiated follicular fluid, granulosa, theca and the oocyte-cumulus complex. Moreover, by transcript quantification using real time PCR, we showed that expression of five key genes in FA metabolism significantly varied between somatic follicular cells (theca, granulosa and cumulus) and the oocyte. In conclusion, lipid metabolism differs between ovarian and follicular compartments. Full article
(This article belongs to the Special Issue Lipid Metabolism)
Figures

Open AccessArticle StAR Protein Stability in Y1 and Kin-8 Mouse Adrenocortical Cells
Biology 2015, 4(1), 200-215; doi:10.3390/biology4010200
Received: 1 December 2014 / Revised: 13 January 2015 / Accepted: 20 February 2015 / Published: 4 March 2015
PDF Full-text (573 KB) | HTML Full-text | XML Full-text
Abstract
The steroidogenic acute regulatory protein (STAR) protein expression is required for cholesterol transport into mitochondria to initiate steroidogenesis in the adrenal and gonads. STAR is synthesized as a 37 kDa precursor protein which is targeted to the mitochondria and imported and processed [...] Read more.
The steroidogenic acute regulatory protein (STAR) protein expression is required for cholesterol transport into mitochondria to initiate steroidogenesis in the adrenal and gonads. STAR is synthesized as a 37 kDa precursor protein which is targeted to the mitochondria and imported and processed to an intra-mitochondrial 30 kDa protein. Tropic hormone stimulation of the cAMP-dependent protein kinase A (PKA) signaling pathway is the major contributor to the transcriptional and post-transcriptional regulation of STAR synthesis. Many studies have focused on the mechanisms of cAMP-PKA mediated control of STAR synthesis while there are few reports on STAR degradation pathways. The objective of this study was to determine the effect of cAMP-PKA-dependent signaling on STAR protein stability. We have used the cAMP-PKA responsive Y1 mouse adrenocortical cells and the PKA-deficient Kin-8 cells to measure STAR phosphorylation and protein half-life. Western blot analysis and standard radiolabeled pulse-chase experiments were used to determine STAR phosphorylation status and protein half-life, respectively. Our data demonstrate that PKA-dependent STAR phosphorylation does not contribute to 30 kDa STAR protein stability in the mitochondria. We further show that inhibition of the 26S proteasome does not block precursor STAR phosphorylation or steroid production in Y1 cells. These data suggest STAR can maintain function and promote steroidogenesis under conditions of proteasome inhibition. Full article
(This article belongs to the Special Issue Lipid Metabolism)
Open AccessArticle The Human ABCG1 Transporter Mobilizes Plasma Membrane and Late Endosomal Non-Sphingomyelin-Associated-Cholesterol for Efflux and Esterification
Biology 2014, 3(4), 866-891; doi:10.3390/biology3040866
Received: 2 October 2014 / Revised: 22 November 2014 / Accepted: 26 November 2014 / Published: 4 December 2014
Cited by 2 | PDF Full-text (1840 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We have previously shown that GFP-tagged human ABCG1 on the plasma membrane (PM) and in late endosomes (LE) mobilizes sterol on both sides of the membrane lipid bilayer, thereby increasing cellular cholesterol efflux to lipid surfaces. In the present study, we examined [...] Read more.
We have previously shown that GFP-tagged human ABCG1 on the plasma membrane (PM) and in late endosomes (LE) mobilizes sterol on both sides of the membrane lipid bilayer, thereby increasing cellular cholesterol efflux to lipid surfaces. In the present study, we examined ABCG1-induced changes in membrane cholesterol distribution, organization, and mobility. ABCG1-GFP expression increased the amount of mobile, non-sphingomyelin(SM)-associated cholesterol at the PM and LE, but not the amount of SM-associated-cholesterol or SM. ABCG1-mobilized non-SM-associated-cholesterol rapidly cycled between the PM and LE and effluxed from the PM to extracellular acceptors, or, relocated to intracellular sites of esterification. ABCG1 increased detergent-soluble pools of PM and LE cholesterol, generated detergent-resistant, non-SM-associated PM cholesterol, and increased resistance to both amphotericin B-induced (cholesterol-mediated) and lysenin-induced (SM-mediated) cytolysis, consistent with altered organization of both PM cholesterol and SM. ABCG1 itself resided in detergent-soluble membrane domains. We propose that PM and LE ABCG1 residing at the phase boundary between ordered (Lo) and disordered (Ld) membrane lipid domains alters SM and cholesterol organization thereby increasing cholesterol flux between Lo and Ld, and hence, the amount of cholesterol available for removal by acceptors on either side of the membrane bilayer for either efflux or esterification. Full article
(This article belongs to the Special Issue Lipid Metabolism)
Figures

Open AccessArticle Cellular Localization and Trafficking of the Human ABCG1 Transporter
Biology 2014, 3(4), 781-800; doi:10.3390/biology3040781
Received: 2 October 2014 / Revised: 23 October 2014 / Accepted: 28 October 2014 / Published: 14 November 2014
PDF Full-text (1968 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We have developed a suitable heterologous cell expression system to study the localization, trafficking, and site(s) of function of the human ABCG1 transporter. Increased plasma membrane (PM) and late endosomal (LE) cholesterol generated by ABCG1 was removed by lipoproteins and liposomes, but [...] Read more.
We have developed a suitable heterologous cell expression system to study the localization, trafficking, and site(s) of function of the human ABCG1 transporter. Increased plasma membrane (PM) and late endosomal (LE) cholesterol generated by ABCG1 was removed by lipoproteins and liposomes, but not apoA-I. Delivery of ABCG1 to the PM and LE was required for ABCG1-mediated cellular cholesterol efflux. ABCG1 LEs frequently contacted the PM, providing a collisional mechanism for transfer of ABCG1-mobilized cholesterol, similar to ABCG1-mediated PM cholesterol efflux to lipoproteins. ABCG1-mobilized LE cholesterol also trafficked to the PM by a non-vesicular pathway. Transfer of ABCG1-mobilized cholesterol from the cytoplasmic face of LEs to the PM and concomitant removal of cholesterol from the outer leaflet of the PM bilayer by extracellular acceptors suggests that ABCG1 mobilizes cholesterol on both sides of the lipid bilayer for removal by acceptors. ABCG1 increased uptake of HDL into LEs, consistent with a potential ABCG1-mediated cholesterol efflux pathway involving HDL resecretion. Thus, ABCG1 at the PM mobilizes PM cholesterol and ABCG1 in LE/LYS generates mobile pools of cholesterol that can traffic by both vesicular and non-vesicular pathways to the PM where it can also be transferred to extracellular acceptors with a lipid surface. Full article
(This article belongs to the Special Issue Lipid Metabolism)
Figures

Open AccessArticle Genetic Risk Scores Associated with Baseline Lipoprotein Subfraction Concentrations Do Not Associate with Their Responses to Fenofibrate
Biology 2014, 3(3), 536-550; doi:10.3390/biology3030536
Received: 23 June 2014 / Revised: 29 July 2014 / Accepted: 5 August 2014 / Published: 25 August 2014
PDF Full-text (335 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewide association [...] Read more.
Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewide association study (GWAS) associated several single nucleotide polymorphisms (SNPs) with lipoprotein measures, and validated these associations in two independent populations. We used this information to construct genetic risk scores (GRSs) for fasting lipoprotein measures at baseline (pre-fenofibrate), and aimed to examine whether these GRSs also associated with the responses of lipoproteins to fenofibrate. Fourteen lipoprotein subclass measures were assayed in 817 men and women before and after a three week fenofibrate trial. We set significance at a Bonferroni corrected alpha <0.05 (p < 0.004). Twelve subclass measures changed with fenofibrate administration (each p = 0.003 to <0.0001). Mixed linear models which controlled for age, sex, body mass index (BMI), smoking status, pedigree and study-center, revealed that GRSs were associated with eight baseline lipoprotein measures (p < 0.004), however no GRS was associated with fenofibrate response. These results suggest that the mechanisms for changes in lipoprotein subclass concentrations with fenofibrate treatment are not mediated by the genetic risk for fasting levels. Full article
(This article belongs to the Special Issue Lipid Metabolism)

Review

Jump to: Research

Open AccessReview Stearoyl-CoA Desaturase-1: Is It the Link between Sulfur Amino Acids and Lipid Metabolism?
Biology 2015, 4(2), 383-396; doi:10.3390/biology4020383
Received: 17 October 2014 / Revised: 2 May 2015 / Accepted: 14 May 2015 / Published: 3 June 2015
Cited by 1 | PDF Full-text (134 KB) | HTML Full-text | XML Full-text
Abstract
An association between sulfur amino acids (methionine, cysteine, homocysteine and taurine) and lipid metabolism has been described in several experimental and population-based studies. Changes in the metabolism of these amino acids influence serum lipoprotein concentrations, although the underlying mechanisms are still poorly [...] Read more.
An association between sulfur amino acids (methionine, cysteine, homocysteine and taurine) and lipid metabolism has been described in several experimental and population-based studies. Changes in the metabolism of these amino acids influence serum lipoprotein concentrations, although the underlying mechanisms are still poorly understood. However, recent evidence has suggested that the enzyme stearoyl-CoA desaturase-1 (SCD-1) may be the link between these two metabolic pathways. SCD-1 is a key enzyme for the synthesis of monounsaturated fatty acids. Its main substrates C16:0 and C18:0 and products palmitoleic acid (C16:1) and oleic acid (C18:1) are the most abundant fatty acids in triglycerides, cholesterol esters and membrane phospholipids. A significant suppression of SCD-1 has been observed in several animal models with disrupted sulfur amino acid metabolism, and the activity of SCD-1 is also associated with the levels of these amino acids in humans. This enzyme also appears to be involved in the etiology of metabolic syndromes because its suppression results in decreased fat deposits (regardless of food intake), improved insulin sensitivity and higher basal energy expenditure. Interestingly, this anti-obesogenic phenotype has also been described in humans and animals with sulfur amino acid disorders, which is consistent with the hypothesis that SCD-1 activity is influenced by these amino acids, in particularly cysteine, which is a strong and independent predictor of SCD-1 activity and fat storage. In this narrative review, we discuss the evidence linking sulfur amino acids, SCD-1 and lipid metabolism. Full article
(This article belongs to the Special Issue Lipid Metabolism)
Open AccessReview Oncostatin M Modulation of Lipid Storage
Biology 2015, 4(1), 151-160; doi:10.3390/biology4010151
Received: 21 November 2014 / Revised: 29 January 2015 / Accepted: 11 February 2015 / Published: 13 February 2015
PDF Full-text (259 KB) | HTML Full-text | XML Full-text
Abstract
Oncostatin M (OSM) is a cytokine belonging to the gp130 family, whose members serve pleiotropic functions. However, several actions of OSM are unique from those of other gp130 cytokines, and these actions may have critical roles in inflammatory mechanisms influencing several metabolic [...] Read more.
Oncostatin M (OSM) is a cytokine belonging to the gp130 family, whose members serve pleiotropic functions. However, several actions of OSM are unique from those of other gp130 cytokines, and these actions may have critical roles in inflammatory mechanisms influencing several metabolic and biological functions of insulin-sensitive tissues. In this review, the actions of OSM in adipose tissue and liver are discussed, with an emphasis on lipid metabolism. Full article
(This article belongs to the Special Issue Lipid Metabolism)
Figures

Open AccessReview Lipids around the Clock: Focus on Circadian Rhythms and Lipid Metabolism
Biology 2015, 4(1), 104-132; doi:10.3390/biology4010104
Received: 10 December 2014 / Accepted: 28 January 2015 / Published: 5 February 2015
Cited by 2 | PDF Full-text (954 KB) | HTML Full-text | XML Full-text
Abstract
Disorders of lipid and lipoprotein metabolism and transport are responsible for the development of a large spectrum of pathologies, ranging from cardiovascular diseases, to metabolic syndrome, even to tumour development. Recently, a deeper knowledge of the molecular mechanisms that control our biological [...] Read more.
Disorders of lipid and lipoprotein metabolism and transport are responsible for the development of a large spectrum of pathologies, ranging from cardiovascular diseases, to metabolic syndrome, even to tumour development. Recently, a deeper knowledge of the molecular mechanisms that control our biological clock and circadian rhythms has been achieved. From these studies it has clearly emerged how the molecular clock tightly regulates every aspect of our lives, including our metabolism. This review analyses the organisation and functioning of the circadian clock and its relevance in the regulation of physiological processes. We also describe metabolism and transport of lipids and lipoproteins as an essential aspect for our health, and we will focus on how the circadian clock and lipid metabolism are greatly interconnected. Finally, we discuss how a deeper knowledge of this relationship might be useful to improve the recent spread of metabolic diseases. Full article
(This article belongs to the Special Issue Lipid Metabolism)
Open AccessReview Will Lipidation of ApoA1 through Interaction with ABCA1 at the Intestinal Level Affect the Protective Functions of HDL?
Biology 2015, 4(1), 17-38; doi:10.3390/biology4010017
Received: 9 October 2014 / Accepted: 18 December 2014 / Published: 6 January 2015
PDF Full-text (850 KB) | HTML Full-text | XML Full-text
Abstract
The relationship between levels of high-density lipoprotein cholesterol (HDL-C) and cardiovascular (CV) risk is well recognized; however, in recent years, large-scale phase III studies with HDL-C-raising or -mimicking agents have failed to demonstrate a clinical benefit on CV outcomes associated with raising [...] Read more.
The relationship between levels of high-density lipoprotein cholesterol (HDL-C) and cardiovascular (CV) risk is well recognized; however, in recent years, large-scale phase III studies with HDL-C-raising or -mimicking agents have failed to demonstrate a clinical benefit on CV outcomes associated with raising HDL-C, casting doubt on the “HDL hypothesis.” This article reviews potential reasons for the observed negative findings with these pharmaceutical compounds, focusing on the paucity of translational models and relevant biomarkers related to HDL metabolism that may have confounded understanding of in vivo mechanisms. A unique function of HDL is its ability to interact with the ATP-binding cassette transporter (ABC) A1 via apolipoprotein (Apo) A1. Only recently, studies have shown that this process may be involved in the intestinal uptake of dietary sterols and antioxidants (vitamin E, lutein and zeaxanthin) at the basolateral surface of enterocytes. This parameter should be assessed for HDL-raising drugs in addition to the more documented reverse cholesterol transport (RCT) from peripheral tissues to the liver. Indeed, a single mechanism involving the same interaction between ApoA1 and ABCA1 may encompass two HDL functions previously considered as separate: antioxidant through the intestinal uptake of antioxidants and RCT through cholesterol efflux from loaded cells such as macrophages. Full article
(This article belongs to the Special Issue Lipid Metabolism)
Open AccessReview Hepatitis C Virus Life Cycle and Lipid Metabolism
Biology 2014, 3(4), 892-921; doi:10.3390/biology3040892
Received: 7 November 2014 / Revised: 4 December 2014 / Accepted: 8 December 2014 / Published: 15 December 2014
Cited by 9 | PDF Full-text (670 KB) | HTML Full-text | XML Full-text
Abstract
Hepatitis C Virus (HCV) infects over 150 million people worldwide. In most cases HCV infection becomes chronic, causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. HCV affects the cholesterol homeostasis and at the molecular level, every step of the [...] Read more.
Hepatitis C Virus (HCV) infects over 150 million people worldwide. In most cases HCV infection becomes chronic, causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. HCV affects the cholesterol homeostasis and at the molecular level, every step of the virus life cycle is intimately connected to lipid metabolism. In this review, we present an update on the lipids and apolipoproteins that are involved in the HCV infectious cycle steps: entry, replication and assembly. Moreover, the result of the assembly process is a lipoviroparticle, which represents a peculiarity of hepatitis C virion. This review illustrates an example of an intricate virus-host interaction governed by lipid metabolism. Full article
(This article belongs to the Special Issue Lipid Metabolism)
Open AccessReview Glycerophosphate/Acylglycerophosphate Acyltransferases
Biology 2014, 3(4), 801-830; doi:10.3390/biology3040801
Received: 12 September 2014 / Revised: 2 November 2014 / Accepted: 5 November 2014 / Published: 19 November 2014
Cited by 7 | PDF Full-text (445 KB) | HTML Full-text | XML Full-text
Abstract
Acyl-CoA:glycerol-3-phosphate acyltransferase (GPAT) and acyl-CoA: 1-acyl-glycerol-3-phosphate acyltransferase (AGPAT) are involved in the de novo synthesis of triacylglycerol (TAG) and glycerophospholipids. Many enzymes belonging to the GPAT/AGPAT family have recently been identified and their physiological or pathophysiological roles have been proposed. The roles [...] Read more.
Acyl-CoA:glycerol-3-phosphate acyltransferase (GPAT) and acyl-CoA: 1-acyl-glycerol-3-phosphate acyltransferase (AGPAT) are involved in the de novo synthesis of triacylglycerol (TAG) and glycerophospholipids. Many enzymes belonging to the GPAT/AGPAT family have recently been identified and their physiological or pathophysiological roles have been proposed. The roles of GPAT/AGPAT in the synthesis of TAG and obesity-related diseases were revealed through the identification of causative genes of these diseases or analyses of genetically manipulated animals. Recent studies have suggested that some isoforms of GPAT/AGPAT family enzymes are involved in the fatty acid remodeling of phospholipids. The enzymology of GPAT/AGPAT and their physiological/ pathological roles in the metabolism of glycerolipids have been described and discussed in this review. Full article
(This article belongs to the Special Issue Lipid Metabolism)
Figures

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Type of Paper: Article
Title: Cellular Localization and Trafficking of the Human ABCG1 Transporter
Authors: Edward B. Neufeld 1,5, Katherine O’Brien 1, Avram D. Walts 1, John A. Stonik 2, Steven J. Demosky, Jr 2, Steven Sabol 2, Daniela Malide 3, Christian A. Combs 3 and Alan T. Remaley 2
Affiliations: 1. Lipid Trafficking Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD USA; E-Mail: neufelde@nhlbi.nih.gov
2. Lipoprotein Metabolism Section, Vascular Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD USA; E-Mail: aremaley1@cc.nih.gov
3. NHLBI Light Microscopy Core Facility, National Institutes of Health, Bethesda, MD USA
4. Lipoprotein and Atherosclerosis Research, Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center
Abstract: We have developed a suitable heterologous cell expression system to study the localization, trafficking, and site(s) of function of the human ABCG1 transporter. Stable expression of GFP-tagged human ABCG1 in a HeLa cell line that lacks endogenous ABCG1, ABCG4 and ABCA1 enhanced cholesterol efflux to liposomes and lipoproteins, but not to apoA-I. ABCG1-GFP expression increased the cholesterol content on the cell surface and endosomes, and this excess cholesterol was removed by HDL. ABCG1-GFP trafficked from its site of synthesis in the ER to the cell surface and then to late endocytic vesicles. BFA and U18666A reduced ABCG1-GFP expression on the cell surface and endosomes as well as ABCG1-mediated cellular cholesterol efflux to HDL, consistent with a role for plasma membrane and endosomal ABCG1 in cholesterol efflux. Monensin blocked delivery of ABCG1-GFP to the cell surface and trapped PM-derived ABCG1-GFP in late endocytic vesicles but did not alter ABCG1-mediated cellular cholesterol efflux, suggesting a role for late endosomal ABCG1 in cholesterol efflux. Hydrolysis of cellular SM markedly enhanced cycling of ABCG1 between endosomes and the cell surface and increased ABCG1-mediated cellular cholesterol efflux to HDL, consistent with a role for ABCG1 (but not SM) cycling between late endosomes and the cell surface in cellular cholesterol efflux. Taken together, these studies establish that ABCG1 at the cell surface and endosomes can generate mobile pools of cholesterol that are available to transfer to extracellular acceptors with a lipid surface.

Type of Paper: Article
Title: The Human ABCG1 Transporter Mobilizes Plasma Membrane and Endosomal Non-Sphingomyelin-Associated Cholesterol for Efflux and Esterification
Authors: Edward B. Neufeld 1,5, Katherine O’Brien 1, Avram D. Walts 1, John A. Stonik 2, Daniela Malide 3, Christian A. Combs 3 and Alan T. Remaley 2
Affiliations: 1. Lipid Trafficking Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD USA; E-Mail: neufelde@nhlbi.nih.gov
2. Lipoprotein Metabolism Section, Vascular Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD USA; E-Mail: aremaley1@cc.nih.gov
3. NHLBI Light Microscopy Core Facility, National Institutes of Health, Bethesda, MD USA
Abstract: We have previously shown that GFP-tagged human ABCG1 on the cell surface and in late endosomes enhances cellular cholesterol efflux to extracellular acceptors with a lipid surface (e.g., HDL, liposomes). In the present study, we examined ABCG1-induced changes in membrane cholesterol distribution, organization, and mobility. ABCG1-GFP expression increased the amount of mobile, non-sphingomyelin(SM)-associated cholesterol at the plasma membrane and endosomes, but did not alter the amount of SM-associated-cholesterol or SM. Non-SM-associated-cholesterol mobilized by ABCG1 rapidly cycled between the cell surface and endosomes and was available for removal from the cell surface by extracellular acceptors, or, relocated to intracellular sites of esterification. ABCG1-GFP expression increased resistance to both amphotericin B- and lysenin-induced cytolysis, and generated a pool of detergent-resistant, non-SM-associated plasma membrane cholesterol, consistent with altered organization of both plasma membrane cholesterol and SM. ABCG1 itself was found to reside in detergent-soluble membrane domains. We propose that plasma membrane and endosomal ABCG1 residing at the phase boundary between ordered (Lo) and disordered (Ld) membrane lipid domains alters SM and cholesterol organization thereby increasing cholesterol flux between Lo and Ld and hence, the amount of cholesterol available for removal by either extracellular (efflux) or intracellular cholesterol acceptors (esterification).

Type of Paper: Article
Title: Genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their responses to fenofibrate
Authors: Alexis C. Frazier-Wood 1,*, Mary K. Wojczynski 2, Ingrid B. Borecki 2, Paul N. Hopkins 3, Chao-Qiang Lai 4, Jose M. Ordovas 4,5,6, Robert J. Straka 7, Micheal Y. Tsai 8, Hemant K. Tiwari 9 and Donna K. Arnett 10
Affiliations: 1. USDA / ARS Children’s Nutrition Research Center, Baylor College of Medicine, Houston, Texas USA; E-Mail: LekkiWood@Gmail.com
2. Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
3. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA
4. Nutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA
5. The Department of Epidemiology and Population Genetics. Centro Nacional Investigación Cardiovasculares (CNIC) Madrid, Spain.
6. IMDEA Food, Madrid, Spain.
7. Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455
8. Department of Laboratory Medicine and Pathology, University of Minnesota, MN
9. Section on Statistical Genetics, University of Alabama at Birmingham, School of Public Health, AL, United States
10. Department of Epidemiology, University of Alabama at Birmingham, School of Public Health, AL, United States
Abstract: Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewide association study (GWAS) associated several single nucleotide polymorphisms (SNPs) with lipoprotein measures, and validated these associations in two independent populations. We used this information to constructed genetic risk scores (GRSs) for fasting lipoprotein measures at baseline (pre-fenofibrate), and aimed to examine whether these GRSs also associated with the responses of lipoproteins to fenofibrate.. Fourteen lipoprotein subclass measures were assayed in 817 men and women before and after a three week fenofibrate trial. We set significance at a Bonferroni corrected alpha<.05 (P<.004). Twelve subclass measures changed with fenofibrate administration (each P=.003-<.0001). Mixed linear models which controlled for age, sex, body mass index (BMI), smoking status, pedigree and study-center, revealed that GRSs were associated with eight baseline lipoprotein measures (P<.004), however no GRS was associated with fenofibrate response. These results suggest that the mechanisms for changes in lipoprotein subclass concentrations with fenofibrate treatment are not mediated by the genetic risk for fasting levels.

Journal Contact

MDPI AG
Biology Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
biology@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Biology
Back to Top