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Apolipoproteins and Lipoproteins in Health and Disease 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 16163

Special Issue Editors

Special Issue Information

Dear Colleagues,

We are pleased to support and edit a new Special Issue for the International Journal of Molecular Sciences, entitled “Apolipoproteins and Lipoproteins in Health and Disease 2.0”. Although apolipoproteins were originally recognized as major determinants in lipoprotein metabolism and cardiovascular disease, the multiple apolipoprotein and lipoprotein classes and subclasses have emerged as relevant participants in multiple biological processes and pathophysiological pathways involved in diabetes, cancer, obesity, neurodegenerative disorders, and inflammatory and infectious diseases.

Leading by Dr. Joan Carles Escolà-Gil and Dr. Noemí Rotllan and assisting by our Topical Advisory Panel Member Dr. Marina Canyelles, this Special Issue aims to publish timely and informative findings on molecular aspects of apolipoproteins (including isoforms and posttranslational modifications) and their influence on health and disease risk. Manuscripts of original research and reviews will be welcome.

Dr. Joan Carles Escolà-Gil
Dr. Noemí Rotllan
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • apolipoproteins
  • Alzheimer's disease
  • atherosclerosis
  • cancer
  • cholesterol
  • diabetes
  • inflammation
  • obesity
  • lipid metabolism
  • lipoproteins

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Published Papers (8 papers)

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Research

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16 pages, 868 KiB  
Article
The Impact of the Mediterranean Diet and Lifestyle Intervention on Lipoprotein Subclass Profiles among Metabolic Syndrome Patients: Findings of a Randomized Controlled Trial
by Beatriz Candás-Estébanez, Bárbara Fernández-Cidón, Emili Corbella, Cristian Tebé, Marta Fanlo-Maresma, Virginia Esteve-Luque, Jordi Salas-Salvadó, Montserrat Fitó, Antoni Riera-Mestre, Emilio Ros and Xavier Pintó
Int. J. Mol. Sci. 2024, 25(2), 1338; https://doi.org/10.3390/ijms25021338 - 22 Jan 2024
Viewed by 1183
Abstract
Metabolic syndrome (MetS) is associated with alterations of lipoprotein structure and function that can be characterized with advanced lipoprotein testing (ADLT). The effect of the Mediterranean diet (MedDiet) and weight loss on the lipoprotein subclass profile has been scarcely studied. Within the PREDIMED-Plus [...] Read more.
Metabolic syndrome (MetS) is associated with alterations of lipoprotein structure and function that can be characterized with advanced lipoprotein testing (ADLT). The effect of the Mediterranean diet (MedDiet) and weight loss on the lipoprotein subclass profile has been scarcely studied. Within the PREDIMED-Plus randomized controlled trial, a sub-study conducted at Bellvitge Hospital recruiting center evaluated the effects of a weight loss program based on an energy-reduced MedDiet (er-MedDiet) and physical activity (PA) promotion (intervention group) compared with energy-unrestricted MedDiet recommendations (control group) on ADLT-assessed lipoprotein subclasses. 202 patients with MetS (n = 107, intervention; n = 95, control) were included. Lipid profiles were determined, and ADLT was performed at baseline, 6, and 12 months. Linear mixed models were used to assess the effects of intervention on lipoprotein profiles. Compared to the control diet, at 12 months, the er-MedDiet+PA resulted in a significant additional 4.2 kg of body weight loss, a decrease in body mass index by 1.4 kg/m2, reduction in waist circumference by 2.2 cm, decreased triglycerides, LDL-cholesterol and non-HDL-cholesterol, and increased HDL-cholesterol. In er-MedDiet+PA participants, ADLT revealed a decrease in small dense-LDL-cholesterol (sd-LDL-C), intermediate-density lipoproteins, VLDL-triglyceride, and HDL-Triglyceride, and an increase in large LDL and large VLDL particles. In conclusion, compared to an ad libitum MedDiet (control group), er-MedDiet+PA decreased plasma triglycerides and the triglyceride content in HDL and VLDL particles, decreased sd-LDL-C, and increased large LDL particles, indicating beneficial changes against cardiovascular disease. Full article
(This article belongs to the Special Issue Apolipoproteins and Lipoproteins in Health and Disease 2.0)
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18 pages, 1976 KiB  
Article
Interplay of Postprandial Triglyceride-Rich Lipoprotein Composition and Adipokines in Obese Adolescents
by Silvia García-Rodríguez, Juan M. Espinosa-Cabello, Aída García-González, Emilio González-Jiménez, María J. Aguilar-Cordero, José M. Castellano and Javier S. Perona
Int. J. Mol. Sci. 2024, 25(2), 1112; https://doi.org/10.3390/ijms25021112 - 16 Jan 2024
Viewed by 715
Abstract
In the context of the alarming rise of infant obesity and its health implications, the present research aims to uncover disruptions in postprandial lipid metabolism and the composition of triglyceride-rich lipoproteins in obese adolescents. A double-blind, controlled clinical trial in the postprandial phase [...] Read more.
In the context of the alarming rise of infant obesity and its health implications, the present research aims to uncover disruptions in postprandial lipid metabolism and the composition of triglyceride-rich lipoproteins in obese adolescents. A double-blind, controlled clinical trial in the postprandial phase on 23 adolescents aged 12 to 16 years was carried out. Twelve participants were categorized as obese (BMI > 30 kg/m2 and percentile > 95) and 11 as normal-weight (BMI = 20–25 kg/m2, percentile 5–85). Blood samples were collected after a 12-h overnight fast and postprandially after consumption of a standardized breakfast containing olive oil, tomato, bread, orange juice, and skimmed milk. Obese adolescents exhibited elevated triglyceride concentrations in both fasting and postprandial states and higher TG/apo-B48 ratios, indicating larger postprandial triglyceride-rich lipoprotein (TRL) particle size, which suggests impaired clearance. Obese subjects also exhibited higher n-6 PUFA concentrations, potentially linked to increased TRL hydrolysis and the release of pro-inflammatory adipokines. In contrast, TRL from normal-weight individuals showed higher concentrations of oleic acid and DHA (n-3 PUFA), with possible anti-inflammatory effects. The results indicate an interplay involving postprandial TRL metabolism and adipokines within the context of adolescent obesity, pointing to potential cardiovascular implications in the future. Full article
(This article belongs to the Special Issue Apolipoproteins and Lipoproteins in Health and Disease 2.0)
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19 pages, 5526 KiB  
Article
Different Dietary Sources of Selenium Alleviate Hepatic Lipid Metabolism Disorder of Heat-Stressed Broilers by Relieving Endoplasmic Reticulum Stress
by Jiayi Wang, Jinzhong Jing, Zhengyi Gong, Jiayong Tang, Longqiong Wang, Gang Jia, Guangmang Liu, Xiaoling Chen, Gang Tian, Jingyi Cai, Bo Kang, Lianqiang Che and Hua Zhao
Int. J. Mol. Sci. 2023, 24(20), 15443; https://doi.org/10.3390/ijms242015443 - 22 Oct 2023
Viewed by 1056
Abstract
As global warming continues, the phenomenon of heat stress (HS) in broilers occurs frequently. The alleviating effect of different selenium (Se) sources on HS-induced hepatic lipid metabolism disorders in broilers remains unclear. This study compared the protective effects of four Se sources (sodium [...] Read more.
As global warming continues, the phenomenon of heat stress (HS) in broilers occurs frequently. The alleviating effect of different selenium (Se) sources on HS-induced hepatic lipid metabolism disorders in broilers remains unclear. This study compared the protective effects of four Se sources (sodium selenite; selenium yeast; selenomethionine; nano-Se) on HS-induced hepatic lipid metabolism disorder and the corresponding response of selenotranscriptome in the liver of broilers. The results showed that HS-induced liver injury and hepatic lipid metabolism disorder, which were reflected in the increased activity of serum alanine aminotransferase (ALT), the increased concentration of triacylglycerol (TG) and total cholesterol (TC), the increased activity of acetyl-CoA carboxylase (ACC), diacylglycerol O-acyltransferase (DGAT) and fatty acid synthase (FAS), and the decreased activity of hepatic lipase (HL) in the liver. The hepatic lipid metabolism disorder was accompanied by the increased mRNA expression of lipid synthesis related-genes, the decreased expression of lipidolysis-related genes, and the increased expression of endoplasmic reticulum (ER) stress biomarkers (PERK, IRE1, ATF6, GRP78). The dietary supplementation of four Se sources exhibited similar protective effects. Four Se sources increased liver Se concentration and promoted the expression of selenotranscriptome and several key selenoproteins, enhanced liver antioxidant capacity and alleviated HS-induced ER stress, and thus resisted the hepatic lipid metabolism disorders of broilers exposed to HS. In conclusion, dietary supplementation of four Se sources (0.3 mg/kg) exhibited similar protective effects on HS-induced hepatic lipid metabolism disorders of broilers, and the protective effect is connected to the relieving of ER stress. Full article
(This article belongs to the Special Issue Apolipoproteins and Lipoproteins in Health and Disease 2.0)
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12 pages, 1830 KiB  
Article
Age, Origin and Functional Study of the Prevalent LDLR Mutation Causing Familial Hypercholesterolaemia in Gran Canaria
by Nicolás M. Suárez, Shifa Jebari-Benslaiman, Roberto Jiménez-Monzón, Asier Benito-Vicente, Yeray Brito-Casillas, Laida Garcés, Ana M. González-Lleo, Antonio Tugores, Mauro Boronat, César Martin, Ana M. Wägner and Rosa M. Sánchez-Hernández
Int. J. Mol. Sci. 2023, 24(14), 11319; https://doi.org/10.3390/ijms241411319 - 11 Jul 2023
Viewed by 771
Abstract
The p.(Tyr400_Phe402del) mutation in the LDL receptor (LDLR) gene is the most frequent cause of familial hypercholesterolaemia (FH) in Gran Canaria. The aim of this study was to determine the age and origin of this prevalent founder mutation and to explore [...] Read more.
The p.(Tyr400_Phe402del) mutation in the LDL receptor (LDLR) gene is the most frequent cause of familial hypercholesterolaemia (FH) in Gran Canaria. The aim of this study was to determine the age and origin of this prevalent founder mutation and to explore its functional consequences. For this purpose, we obtained the haplotypic information of 14 microsatellite loci surrounding the mutation in one homozygous individual and 11 unrelated heterozygous family trios. Eight different mutation carrier haplotypes were identified, which were estimated to originate from a common ancestral haplotype 387 (110–1572) years ago. This estimation suggests that this mutation happened after the Spanish colonisation of the Canary Islands, which took place during the fifteenth century. Comprehensive functional studies of this mutation showed that the expressed LDL receptor was retained in the endoplasmic reticulum, preventing its migration to the cell surface, thus allowing us to classify this LDLR mutation as a class 2a, defective, pathogenic variant. Full article
(This article belongs to the Special Issue Apolipoproteins and Lipoproteins in Health and Disease 2.0)
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12 pages, 1089 KiB  
Article
Eicosapentaenoic and Docosahexaenoic Acid Supplementation Increases HDL Content in n-3 Fatty Acids and Improves Endothelial Function in Hypertriglyceridemic Patients
by Paola Peña-de-la-Sancha, Adolfo Muñoz-García, Nilda Espínola-Zavaleta, Rocío Bautista-Pérez, Ana María Mejía, María Luna-Luna, Victoria López-Olmos, José-Manuel Rodríguez-Pérez, José-Manuel Fragoso, Elizabeth Carreón-Torres and Óscar Pérez-Méndez
Int. J. Mol. Sci. 2023, 24(6), 5390; https://doi.org/10.3390/ijms24065390 - 11 Mar 2023
Cited by 4 | Viewed by 1577
Abstract
High-density lipoproteins (HDLs) are known to enhance vascular function through different mechanisms, including the delivery of functional lipids to endothelial cells. Therefore, we hypothesized that omega-3 (n-3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content of HDLs would improve the beneficial vascular effects [...] Read more.
High-density lipoproteins (HDLs) are known to enhance vascular function through different mechanisms, including the delivery of functional lipids to endothelial cells. Therefore, we hypothesized that omega-3 (n-3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content of HDLs would improve the beneficial vascular effects of these lipoproteins. To explore this hypothesis, we performed a placebo-controlled crossover clinical trial in 18 hypertriglyceridemic patients without clinical symptoms of coronary heart disease who received highly purified EPA 460 mg and DHA 380 mg, twice a day for 5 weeks or placebo. After 5 weeks of treatment, patients followed a 4-week washout period before crossover. HDLs were isolated using sequential ultracentrifugation for characterization and determination of fatty acid content. Our results showed that n-3 supplementation induced a significant decrease in body mass index, waist circumference as well as triglycerides and HDL-triglyceride plasma concentrations, whilst HDL-cholesterol and HDL-phospholipids significantly increased. On the other hand, HDL, EPA, and DHA content increased by 131% and 62%, respectively, whereas 3 omega-6 fatty acids significantly decreased in HDL structures. In addition, the EPA-to-arachidonic acid (AA) ratio increased more than twice within HDLs suggesting an improvement in their anti-inflammatory properties. All HDL-fatty acid modifications did not affect the size distribution or the stability of these lipoproteins and were concomitant with a significant increase in endothelial function assessed using a flow-mediated dilatation test (FMD) after n-3 supplementation. However, endothelial function was not improved in vitro using a model of rat aortic rings co-incubated with HDLs before or after treatment with n-3. These results suggest a beneficial effect of n-3 on endothelial function through a mechanism independent of HDL composition. In conclusion, we demonstrated that EPA and DHA supplementation for 5 weeks improved vascular function in hypertriglyceridemic patients, and induced enrichment of HDLs with EPA and DHA to the detriment of some n-6 fatty acids. The significant increase in the EPA-to-AA ratio in HDLs is indicative of a more anti-inflammatory profile of these lipoproteins. Full article
(This article belongs to the Special Issue Apolipoproteins and Lipoproteins in Health and Disease 2.0)
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Review

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22 pages, 1695 KiB  
Review
Circadian Regulation of Apolipoproteins in the Brain: Implications in Lipid Metabolism and Disease
by Chaeeun Hannah Lee, Charlotte Ellzabeth Murrell, Alexander Chu and Xiaoyue Pan
Int. J. Mol. Sci. 2023, 24(24), 17415; https://doi.org/10.3390/ijms242417415 - 12 Dec 2023
Viewed by 965
Abstract
The circadian rhythm is a 24 h internal clock within the body that regulates various factors, including sleep, body temperature, and hormone secretion. Circadian rhythm disruption is an important risk factor for many diseases including neurodegenerative illnesses. The central and peripheral oscillators’ circadian [...] Read more.
The circadian rhythm is a 24 h internal clock within the body that regulates various factors, including sleep, body temperature, and hormone secretion. Circadian rhythm disruption is an important risk factor for many diseases including neurodegenerative illnesses. The central and peripheral oscillators’ circadian clock network controls the circadian rhythm in mammals. The clock genes govern the central clock in the suprachiasmatic nucleus (SCN) of the brain. One function of the circadian clock is regulating lipid metabolism. However, investigations of the circadian regulation of lipid metabolism-associated apolipoprotein genes in the brain are lacking. This review summarizes the rhythmic expression of clock genes and lipid metabolism-associated apolipoprotein genes within the SCN in Mus musculus. Nine of the twenty apolipoprotein genes identified from searching the published database (SCNseq and CircaDB) are highly expressed in the SCN. Most apolipoprotein genes (ApoE, ApoC1, apoA1, ApoH, ApoM, and Cln) show rhythmic expression in the brain in mice and thus might be regulated by the master clock. Therefore, this review summarizes studies on lipid-associated apolipoprotein genes in the SCN and other brain locations, to understand how apolipoproteins associated with perturbed cerebral lipid metabolism cause multiple brain diseases and disorders. This review describes recent advancements in research, explores current questions, and identifies directions for future research. Full article
(This article belongs to the Special Issue Apolipoproteins and Lipoproteins in Health and Disease 2.0)
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16 pages, 708 KiB  
Review
Apolipoprotein D as a Potential Biomarker in Neuropsychiatric Disorders
by Eva del Valle, Nuria Rubio-Sardón, Carlota Menéndez-Pérez, Eva Martínez-Pinilla and Ana Navarro
Int. J. Mol. Sci. 2023, 24(21), 15631; https://doi.org/10.3390/ijms242115631 - 26 Oct 2023
Viewed by 1093
Abstract
Neuropsychiatric disorders (NDs) are a diverse group of pathologies, including schizophrenia or bipolar disorders, that directly affect the mental and physical health of those who suffer from them, with an incidence that is increasing worldwide. Most NDs result from a complex interaction of [...] Read more.
Neuropsychiatric disorders (NDs) are a diverse group of pathologies, including schizophrenia or bipolar disorders, that directly affect the mental and physical health of those who suffer from them, with an incidence that is increasing worldwide. Most NDs result from a complex interaction of multiple genes and environmental factors such as stress or traumatic events, including the recent Coronavirus Disease (COVID-19) pandemic. In addition to diverse clinical presentations, these diseases are heterogeneous in their pathogenesis, brain regions affected, and clinical symptoms, making diagnosis difficult. Therefore, finding new biomarkers is essential for the detection, prognosis, response prediction, and development of new treatments for NDs. Among the most promising candidates is the apolipoprotein D (Apo D), a component of lipoproteins implicated in lipid metabolism. Evidence suggests an increase in Apo D expression in association with aging and in the presence of neuropathological processes. As a part of the cellular neuroprotective defense machinery against oxidative stress and inflammation, changes in Apo D levels have been demonstrated in neuropsychiatric conditions like schizophrenia (SZ) or bipolar disorders (BPD), not only in some brain areas but in corporal fluids, i.e., blood or serum of patients. What is not clear is whether variation in Apo D quantity could be used as an indicator to detect NDs and their progression. This review aims to provide an updated view of the clinical potential of Apo D as a possible biomarker for NDs. Full article
(This article belongs to the Special Issue Apolipoproteins and Lipoproteins in Health and Disease 2.0)
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19 pages, 1980 KiB  
Review
Advances in Treatment of Dyslipidemia
by Jill Dybiec, Wiktoria Baran, Bartłomiej Dąbek, Piotr Fularski, Ewelina Młynarska, Ewa Radzioch, Jacek Rysz and Beata Franczyk
Int. J. Mol. Sci. 2023, 24(17), 13288; https://doi.org/10.3390/ijms241713288 - 27 Aug 2023
Cited by 2 | Viewed by 7894
Abstract
Dyslipidemias have emerged as prevalent disorders among patients, posing significant risks for the development and progression of cardiovascular diseases. These conditions are characterized by elevated levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C). This review delves into the current [...] Read more.
Dyslipidemias have emerged as prevalent disorders among patients, posing significant risks for the development and progression of cardiovascular diseases. These conditions are characterized by elevated levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C). This review delves into the current treatment approach, focusing on equalizing these parameters while enhancing the overall quality of life for patients. Through an extensive analysis of clinical trials, we identify disorders that necessitate alternative treatment strategies, notably familial hypercholesterolemia. The primary objective of this review is to consolidate existing information concerning drugs with the potential to revolutionize dyslipidemia management significantly. Among these promising pharmaceuticals, we highlight alirocumab, bempedoic acid, antisense oligonucleotides, angiopoietin-like protein inhibitors, apolipoprotein C-III (APOC3) inhibitors, lomitapide, and cholesterol ester transfer protein (CETP) inhibitors. Our review demonstrates the pivotal roles played by each of these drugs in targeting specific parameters of lipid metabolism. We outline the future landscape of dyslipidemia treatment, envisaging a more tailored and effective therapeutic approach to address this widespread medical concern. Full article
(This article belongs to the Special Issue Apolipoproteins and Lipoproteins in Health and Disease 2.0)
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