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The Lipid Metabolism in Health and Diseases
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The Lipid Metabolism in Health and Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 58419

Special Issue Editors

Dr. Anca Sima

E-Mail Website
Guest Editor
Lipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu”, 8, B.P. Hasdeu Street, 050568 Bucharest, Romania
Interests: lipid metabolism in health and diseases; cellular biology and biochemistry of blood vessels; novel biomarkers for cardiovascular disease; genetic and epigenetic mechanisms of atherosclerosis and/or diabetes; pharmacologic attempts to arrest or reverse cardiovascular diseases
Dr. Loredan Stefan Niculescu

E-Mail Website
Co-Guest Editor
Head of Molecular Biology of Lipoproteins Laboratory, Lipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Bucharest, Romania
Interests: Non-coding RNAs; microRNAs; RNA-related epigenetic alterations in dyslipidemia; atherosclerosis and diabetes; disease biomarkers; bioinformatics; in vivo modulation of microRNAs
Special Issues, Collections and Topics in MDPI journals
Dr. Camelia Sorina Stancu

E-Mail Website
Co-Guest Editor
Head of Lipoproteins and Atherosclerosis Laboratory, Lipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Bucharest, Romania
Interests: Lipoproteins composition and their biosynthesis in the liver and small intestine; modified lipoproteins and their effects on the cells of the arterial wall; animal models and cell culture; anti-atherosclerotic therapies
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Maria I. Dorobantu

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Co-Guest Editor
1. Corresponding member of the Romanian Academiy, 125, Calea Victoriei, Sector 1, RO - 010071 Bucharest, Romania
2. Department 4-Cardiothoracic Pathology, University of Medicine and Pharmacy Carol Davila, 8, Eroii Sanitari Bvd., 050474 Bucharest, Romania
Interests: ischemic heart disease; atherosclerosis; molecular mechanisms of acute coronary syndromes; arterial hypertension; hypertensive target organ damage
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lipids play essential roles in the organization and function of cells, contribute to the structural integrity of cellular membranes, mediate signal transduction, and regulate energy metabolism. Lipid metabolism comprises very complex processes of the synthesis and degradation of lipids under the control of gene regulated proteins, but their connections are still incompletely known. The dysregulation of lipid metabolism plays a major role in the etiology and evolution of inflammatory disorders, cardiometabolic and neurological diseases, and several forms of cancer. Technical advances, including functional genomics, metabolomics, lipidomics, and lipid–protein interaction maps, have uncovered new ways to control molecular mechanisms mediating lipid function. The discovery of genetic and epigenetic factors in health and disease, either linked to DNA modifications or non-coding RNAs, has opened new research opportunities to decipher the mechanisms to control lipid metabolism and to forward the management of various diseases. The identification of new therapeutic targets and the development of new approaches in the therapy of the above-mentioned pathologies have led to revolutionary therapies to prolong the life expectancy of patients with cardiovascular diseases, diabetes, metabolic syndrome, or cancer, but residual risks of life-threatening events still remain.

The purpose of this Special Issue is to promote papers focused on the newly deciphered mechanisms of lipid metabolism and their alterations in various diseases. Moreover, this Special Issue aims to highlight novel molecular targets for future innovative therapies designed to amend lipid metabolism disorders with remarkable results in treating the aforementioned pathologies. Therefore, we invite investigators to contribute with high-quality, original research and review articles addressing the purpose of this Special Issue.

Dr. Anca Sima
Dr. Loredan Stefan Niculescu
Dr. Camelia Sorina Stancu
Prof. Dr. Maria I. Dorobantu 
Guest Editors

Manuscript Submission Information

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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. Biomedicines 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 2600 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

  • lipids
  • lipoproteins
  • cell signaling
  • epigenetic factors
  • atherosclerosis
  • diabetes
  • obesity
  • fatty liver disease
  • cancer
  • non-coding RNAs
  • disease biomarkers
  • therapies

Published Papers (21 papers)

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21 pages, 4299 KiB  
Article
Sex-Specific Patterns of Diaphragm Phospholipid Content and Remodeling during Aging and in a Model of SELENON-Related Myopathy
by Rezlène Bargui, Audrey Solgadi, Florent Dumont, Bastien Prost, Nathalie Vadrot, Anne Filipe, Andrew T. V. Ho, Ana Ferreiro and Maryline Moulin
Biomedicines 2023, 11(2), 234; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11020234 - 17 Jan 2023
Viewed by 1492
Abstract
Growing evidence shows that the lipid bilayer is a key site for membrane interactions and signal transduction. Surprisingly, phospholipids have not been widely studied in skeletal muscles, although mutations in genes involved in their biosynthesis have been associated with muscular diseases. Using mass [...] Read more.
Growing evidence shows that the lipid bilayer is a key site for membrane interactions and signal transduction. Surprisingly, phospholipids have not been widely studied in skeletal muscles, although mutations in genes involved in their biosynthesis have been associated with muscular diseases. Using mass spectrometry, we performed a phospholipidomic profiling in the diaphragm of male and female, young and aged, wild type and SelenoN knock-out mice, the murine model of an early-onset inherited myopathy with severe diaphragmatic dysfunction. We identified 191 phospholipid (PL) species and revealed an important sexual dimorphism in PLs in the diaphragm, with almost 60% of them being significantly different between male and female animals. In addition, 40% of phospholipids presented significant age-related differences. Interestingly, SELENON protein absence was responsible for remodeling of 10% PL content, completely different in males and in females. Expression of genes encoding enzymes involved in PL remodeling was higher in males compared to females. These results establish the diaphragm PL map and highlight an important PL remodeling pattern depending on sex, aging and partly on genotype. These differences in PL profile may contribute to the identification of biomarkers associated with muscular diseases and muscle aging. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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18 pages, 4611 KiB  
Article
HCV Infection and Liver Cirrhosis Are Associated with a Less-Favorable Serum Cholesteryl Ester Profile Which Improves through the Successful Treatment of HCV
by Kilian Weigand, Georg Peschel, Jonathan Grimm, Martina Müller, Marcus Höring, Sabrina Krautbauer, Gerhard Liebisch and Christa Buechler
Biomedicines 2022, 10(12), 3152; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10123152 - 06 Dec 2022
Cited by 1 | Viewed by 1149
Abstract
Background: Infection with hepatitis C virus (HCV) lowers serum cholesterol levels, which rapidly recover during therapy with direct-acting antivirals (DAAs). Serum cholesterol is also reduced in patients with liver cirrhosis. Studies investigating serum cholesterol in patients with chronic liver diseases are generally [...] Read more.
Background: Infection with hepatitis C virus (HCV) lowers serum cholesterol levels, which rapidly recover during therapy with direct-acting antivirals (DAAs). Serum cholesterol is also reduced in patients with liver cirrhosis. Studies investigating serum cholesterol in patients with chronic liver diseases are generally based on enzymatic assays providing total cholesterol levels. Hence, these studies do not account for the individual cholesteryl ester (CE) species, which have different properties according to acyl chain length and desaturation. Methods: Free cholesterol (FC) and 15 CE species were quantified by flow injection analysis high-resolution Fourier Transform mass spectrometry (FIA-FTMS) in the serum of 178 patients with chronic HCV before therapy and during treatment with DAAs. Results: Serum CEs were low in HCV patients with liver cirrhosis and, compared to patients without cirrhosis, proportions of CE 16:0 and 16:1 were higher whereas % CE 20:4 and 20:5 were reduced. FC levels were unchanged, and the CE/FC ratio was consequently low in cirrhosis. FC and CEs did not correlate with viral load. Four CE species were reduced in genotype 3 compared to genotype 1-infected patients. During DAA therapy, 9 of the 15 measured CE species, and the CE/FC ratio, increased. Relative to total CE levels, % CE 16:0 declined and % CE 18:3 was higher at therapy end. At this time, % CE 14:0, 16:0 and 16:1 were higher and % CE 20:4 and 22:6 were lower in the cirrhosis than the non-cirrhosis patients. Viral genotype associated changes of CEs disappeared at therapy end. Conclusions: The serum CE composition differs between patients with and without liver cirrhosis, and changes through the efficient elimination of HCV. Overall, HCV infection and cirrhosis are associated with a higher proportion of CE species with a lower number of carbon atoms and double bonds, reflecting a less-favorable CE profile. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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13 pages, 1501 KiB  
Article
Effect of N-3 Polyunsaturated Fatty Acids on Lipid Composition in Familial Hypercholesterolemia: A Randomized Crossover Trial
by Liv Nesse Hande, Christian Kjellmo, Kristin Pettersen, Stefan Ljunggren, Helen Karlsson, Karin Cederbrant, Maritha Marcusson-Ståhl, Anders Hovland and Knut Tore Lappegård
Biomedicines 2022, 10(8), 1809; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10081809 - 27 Jul 2022
Cited by 3 | Viewed by 2850
Abstract
Individuals with familial hypercholesterolemia (FH) have an increased risk of cardiovascular disease. Treatment is mainly low-density lipoprotein cholesterol (LDL-C) reduction. How omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplements affect lipoproteins in FH subjects is unknown. We hypothesized that a high-dose n-3 PUFA supplement [...] Read more.
Individuals with familial hypercholesterolemia (FH) have an increased risk of cardiovascular disease. Treatment is mainly low-density lipoprotein cholesterol (LDL-C) reduction. How omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplements affect lipoproteins in FH subjects is unknown. We hypothesized that a high-dose n-3 PUFA supplement would reduce atherogenic lipoproteins and influence the high-density lipoprotein cholesterol (HDL-C) function. We performed a randomized, double-blinded crossover study with 34 genetically verified FH individuals (18–75 years, clinically stable, statin treatment > 12 months). Treatment was 4 g n-3 PUFAs (1840 mg eicosapentaenoic acid and 1520 mg docosahexaenoic acid daily) or four capsules of olive oil for three months in a crossover design with a washout period of three months. The defined outcomes were changes in triglycerides, lipoproteins, lipoprotein subfractions, apolipoproteins, and HDL-C function. After treatment with n-3 PUFAs, total cholesterol, LDL-C, and triglycerides were reduced compared to placebo (p ≤ 0.01 for all). Total HDL-C levels were unchanged, but the subfraction of large HDL-C was higher (p ≤ 0.0001) after n-3 PUFAs than after placebo, and intermediate HDL-C and small HDL-C were reduced after n-3 PUFAs compared to placebo (p = 0.02 and p ≤ 0.001, respectively). No changes were found in apolipoproteins and HDL-C function. N-3 PUFAs supplements reduced atherogenic lipoproteins in FH subjects, leaving HDL-C function unaffected. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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19 pages, 4954 KiB  
Article
N-3 PUFA Ameliorates the Gut Microbiota, Bile Acid Profiles, and Neuropsychiatric Behaviours in a Rat Model of Geriatric Depression
by Te-Hsuan Tung, Yang-Ching Chen, Ya-Tin Lin and Shih-Yi Huang
Biomedicines 2022, 10(7), 1594; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10071594 - 04 Jul 2022
Cited by 8 | Viewed by 2434
Abstract
The brain−gut−microbiome (BGM) axis affects host bioinformation. N-3 polyunsaturated fatty acids (PUFAs) alleviate cognitive impairment and depression in older adults. This study investigated altered microbiota−bile acid signalling as a potential mechanism linking fish oil-induced gut changes in microbiota to alleviate psychological symptoms. Sprague [...] Read more.
The brain−gut−microbiome (BGM) axis affects host bioinformation. N-3 polyunsaturated fatty acids (PUFAs) alleviate cognitive impairment and depression in older adults. This study investigated altered microbiota−bile acid signalling as a potential mechanism linking fish oil-induced gut changes in microbiota to alleviate psychological symptoms. Sprague Dawley rats were fed a fish oil diet and administered D-galactose combined with chronic unpredictable mild stress (CUMS) to simulate geriatric depression. The cognitive function, psychological symptoms, microbiota compositions, and faecal bile acid profiles of the rats were assessed thereafter. A correlation analysis was conducted to determine whether the fish oil-induced alteration of the rats’ microbiota and bile acid profiles affected the rats’ behaviour. D-galactose and CUMS resulted in lower concentrations of Firmicutes, significantly altered bile acid profiles, and abnormal neurobehaviours. Fish oil intake alleviated the rats’ emotional symptoms and increased the abundance of Bacteroidetes, Prevotellaceae, Marinifilaceae, and Bacteroidesuniformis. It also elevated the concentrations of primary bile acids and taurine-conjugated bile acids in the rats’ faeces. The rats’ taurine-conjugated bile acid levels were significantly correlated with their behavioural outcomes. In short, fish oil intake may alleviate psychological symptoms by altering the microbial metabolites involved in the BGM axis, especially in the conjugation of bile acids. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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16 pages, 2480 KiB  
Article
Rottlerin Stimulates Exosome/Microvesicle Release Via the Increase of Ceramide Levels Mediated by Ampk in an In Vitro Model of Intracellular Lipid Accumulation
by Yessenia L. Molina, David García-Seisdedos, Bohdan Babiy, Milagros Lerma, Javier Martínez-Botas, María J. Casarejos, María T. Vallejo, Diego Gómez-Coronado, Miguel A. Lasunción, Óscar Pastor and Rebeca Busto
Biomedicines 2022, 10(6), 1316; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10061316 - 03 Jun 2022
Cited by 2 | Viewed by 2061
Abstract
Exosomes/microvesicles originate from multivesicular bodies that allow the secretion of endolysosome components out of the cell. In the present work, we investigated the effects of rottlerin, a polyphenol, on exosome/microvesicle secretion in a model of intracellular lipid trafficking impairment, and elucidated the mechanism [...] Read more.
Exosomes/microvesicles originate from multivesicular bodies that allow the secretion of endolysosome components out of the cell. In the present work, we investigated the effects of rottlerin, a polyphenol, on exosome/microvesicle secretion in a model of intracellular lipid trafficking impairment, and elucidated the mechanism of action. In a model of lipid trafficking impairment in C6 glia cells, rottlerin increased ceramide levels, while decreasing hexosylceramide content. This was accompanied by increased exosome/microvesicle secretion, thereby reducing the concentration of lipids in the endolysosomal compartment. The reduction of hexosylceramide levels by rottlerin was attributed to the increase of β-glucosidase (glucosylceramidase) activity, and the effects of rottlerin were abrogated by β-glucosidase inhibitors such as isofagomine D-tartrate and AMP-deoxynojirimycin. Moreover, treatment with ML-266, a potent activator of the β-glucosidase enzyme, recapitulated the effects of rottlerin on the sphingolipid profile and exosome/microvesicle secretion. Finally, inhibition of AMPK (AMP-activated protein kinase) using compound C prevented both exosome/microvesicle secretion and the elimination of endolysosome lipids, which were promoted by rottlerin. The results showed that the decrease in intracellular lipid deposition induced by rottlerin was mediated by β-glucosidase activation and exosome/microvesicle release via the AMPK pathway. Rottlerin consumption could represent an additional health benefit in lysosomal deposition diseases. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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20 pages, 4635 KiB  
Article
Lipidomics Analysis of Free Fatty Acids in Human Plasma of Healthy and Diabetic Subjects by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS)
by Maroula G. Kokotou, Christiana Mantzourani, Charikleia S. Batsika, Olga G. Mountanea, Ioanna Eleftheriadou, Ourania Kosta, Nikolaos Tentolouris and George Kokotos
Biomedicines 2022, 10(5), 1189; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051189 - 20 May 2022
Cited by 5 | Viewed by 2612
Abstract
Targeted analytical methods for the determination of free fatty acids (FFAs) in human plasma are of high interest because they may help in identifying biomarkers for diseases and in monitoring the progress of a disease. The determination of FFAs is of particular importance [...] Read more.
Targeted analytical methods for the determination of free fatty acids (FFAs) in human plasma are of high interest because they may help in identifying biomarkers for diseases and in monitoring the progress of a disease. The determination of FFAs is of particular importance in the case of metabolic disorders because FFAs have been associated with diabetes. We present a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method, which allows the simultaneous determination of 74 FFAs in human plasma. The method is fast (10-min run) and straightforward, avoiding any derivatization step and tedious sample preparation. A total of 35 standard saturated and unsaturated FFAs, as well as 39 oxygenated (either hydroxy or oxo) saturated FFAs, were simultaneously detected and quantified in plasma samples from 29 subjects with type 2 diabetes mellitus (T2D), 14 with type 1 diabetes mellitus (T1D), and 28 healthy subjects. Alterations in the levels of medium-chain FFAs (C6:0 to C10:0) were observed between the control group and T2D and T1D patients. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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17 pages, 3024 KiB  
Article
Low Density Lipoprotein Exposure of Plasmacytoid Dendritic Cells Blunts Toll-like Receptor 7/9 Signaling via NUR77
by Anette Christ, Pieter G. Goossens, Erwin Wijnands, Han Jin, Bart Legein, Tammy Oth, Aaron Isaacs, Monika Stoll, Joris Vanderlocht, Esther Lutgens, Mat J. A. P. Daemen, Martin Zenke and Erik A. L. Biessen
Biomedicines 2022, 10(5), 1152; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051152 - 17 May 2022
Cited by 2 | Viewed by 1923
Abstract
Background: Pathogens or trauma-derived danger signals induced maturation and activation of plasmacytoid dendritic cells (pDCs) is a pivotal step in pDC-dependent host defense. Exposure of pDC to cardiometabolic disease-associated lipids and proteins may well influence critical signaling pathways, thereby compromising immune responses against [...] Read more.
Background: Pathogens or trauma-derived danger signals induced maturation and activation of plasmacytoid dendritic cells (pDCs) is a pivotal step in pDC-dependent host defense. Exposure of pDC to cardiometabolic disease-associated lipids and proteins may well influence critical signaling pathways, thereby compromising immune responses against endogenous, bacterial and viral pathogens. In this study, we have addressed if hyperlipidemia impacts human pDC activation, cytokine response and capacity to prime CD4+ T cells. METHODS AND RESULTS: We show that exposure to pro-atherogenic oxidized low-density lipoproteins (oxLDL) led to pDC lipid accumulation, which in turn ablated a Toll-like receptor (TLR) 7 and 9 dependent up-regulation of pDC maturation markers CD40, CD83, CD86 and HLA-DR. Moreover, oxLDL dampened TLR9 activation induced the production of pro-inflammatory cytokines in a NUR77/IRF7 dependent manner and impaired the capacity of pDCs to prime and polarize CD4+ T helper (Th) cells. CONCLUSION: Our findings reveal profound effects of dyslipidemia on pDC responses to pathogen-derived signals. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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14 pages, 2019 KiB  
Article
Breast Milk from Non-Obese Women with a High Omega-6 to Omega-3 Fatty Acid Ratio, but Not from Women with Obesity, Increases Lipogenic Gene Expression in 3T3-L1 Preadipocytes, Suggesting Adipocyte Dysfunction
by Peter Isesele, Samantha Enstad, Pham Huong, Raymond Thomas, Carol L. Wagner, Sarbattama Sen and Sukhinder K. Cheema
Biomedicines 2022, 10(5), 1129; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051129 - 13 May 2022
Cited by 4 | Viewed by 2699
Abstract
Maternal body mass index is associated with breast milk (BM) fatty acid composition. This study investigated the effects of BM omega (n)-6:n-3 polyunsaturated fatty acids (PUFAs) from non-obese women and women with obesity on the process of adipogenesis in 3T3-L1 preadipocytes. BM samples [...] Read more.
Maternal body mass index is associated with breast milk (BM) fatty acid composition. This study investigated the effects of BM omega (n)-6:n-3 polyunsaturated fatty acids (PUFAs) from non-obese women and women with obesity on the process of adipogenesis in 3T3-L1 preadipocytes. BM samples were collected from non-obese women (BMNO) and women with obesity (BMO) at one month postpartum. The fatty acid composition was measured, and BMNO and BMO groups with the lowest (Q1) and highest (Q4) quartiles of n-6:n-3 PUFA ratios were identified. 3T3-L1 preadipocytes were differentiated in the presence or absence of BM. Lipid accumulation and the expression of genes involved in lipogenesis and lipolysis were measured. Treatment with BMNO containing high (vs. low) n-6:n-3 PUFA ratios significantly increased the mRNA expression of lipogenic genes (acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase); however, there was no effect when cells were treated with BMO (with either low or high n-6:n-3 PUFA ratios). Treatment with BMO (high n-6:n-3 PUFA ratio) caused larger lipid droplets. Our findings demonstrated that BMNO with a high n-6:n-3 PUFA ratio was associated with a higher expression of lipogenic genes, while BMO with a high n-6:n-3 PUFA ratio showed larger lipid droplets, suggesting adipocyte dysfunction. These findings may have implications in the BM-mediated programming of childhood obesity. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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16 pages, 2086 KiB  
Article
Remodeling of the Dermal Extracellular Matrix in a Tissue-Engineered Psoriatic Skin Model by n-3 Polyunsaturated Fatty Acids
by Mélissa Simard, Alexe Grenier, Geneviève Rioux, Andréa Tremblay, Isalie Blais, Nicolas Flamand and Roxane Pouliot
Biomedicines 2022, 10(5), 1078; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051078 - 06 May 2022
Cited by 7 | Viewed by 2197
Abstract
Psoriasis is an inflammatory skin disease mainly associated with an epidermal disorder. However, the involvement of the dermal extracellular matrix (ECM) composition in psoriasis is still poorly understood. This study aimed to investigate the expression of ECM components in psoriatic skin substitutes (PS [...] Read more.
Psoriasis is an inflammatory skin disease mainly associated with an epidermal disorder. However, the involvement of the dermal extracellular matrix (ECM) composition in psoriasis is still poorly understood. This study aimed to investigate the expression of ECM components in psoriatic skin substitutes (PS−) compared with healthy skin substitutes (HS−), as well as the effect of an n-3 polyunsaturated fatty acid, namely α-linolenic acid (ALA), on the psoriatic dermal compartment (PSALA+). Liquid chromatography tandem mass spectrometry analyses revealed that the lipidome of PS− contained higher amounts of n-6 derived prostaglandins (PGE2) and lipoxygenase products (9-HODE and 15-HETE). ALA supplementation increased the levels of PGE3, 13-HOTrE, 15-HEPE, and 18-HEPE, and decreased the levels of PGE2, 15-HETE, and 9-HOPE compared with PS−, indicating that ALA modulates the dermal lipidome of psoriatic skin substitutes. Gene expression profiling showed that several genes encoding for different ECM proteins were overexpressed in PS− compared with HS−, namely COL1A1 (4.2-fold), COL1A2 (3-fold), COL3A1 (4.4-fold), COL4A1 (2.3-fold), COL4A2 (6.3-fold), COL5A1 (3.3-fold), COL5A2 (5.2-fold), and COL5A3 (4.6-fold). Moreover, the expression of collagen IV (Col IV), collagen VII (Col VII), and laminin was found to be increased in PS− compared with HS−, and to be restored with ALA (PSALA+) according to immunofluorescence staining, while only the collagen I to collagen III ratio was altered according to dot blot analyses. Linear regression analysis revealed several positive correlations, including Col III with 14-HDHA levels, fibronectin with 12-HETE and 15-HETE levels, the dermo-epidermal junction Col IV with PGF2α, 9-HODE, and 13-HODE levels, and laminin with levels of PGF2α, 9-HODE, 13-HODE, 5-HETE, 12-HETE, and 15-HETE. These results suggest that the ECM plays an underestimated role in the pathogenesis of psoriasis and that ALA supplementation can regulate the ECM composition. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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16 pages, 4742 KiB  
Article
Accumulation of Arachidonic Acid, Precursor of Pro-Inflammatory Eicosanoids, in Adipose Tissue of Obese Women: Association with Breast Cancer Aggressiveness Indicators
by Lobna Ouldamer, Marie-Lise Jourdan, Michelle Pinault, Flavie Arbion and Caroline Goupille
Biomedicines 2022, 10(5), 995; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10050995 - 26 Apr 2022
Cited by 6 | Viewed by 2171
Abstract
While obesity is linked to cancer risk, no studies have explored the consequences of body mass index (BMI) on fatty acid profiles in breast adipose tissue and on breast tumor aggressiveness indicators. Because of this, 261 breast adipose tissue samples of women with [...] Read more.
While obesity is linked to cancer risk, no studies have explored the consequences of body mass index (BMI) on fatty acid profiles in breast adipose tissue and on breast tumor aggressiveness indicators. Because of this, 261 breast adipose tissue samples of women with invasive breast carcinoma were analyzed. Fatty acid profile was established by gas chromatography. For normal-weight women, major changes in fatty acid profile occurs after menopause, with the enrichment of long-chain polyunsaturated fatty acids (LC-PUFAs) of both n-6 and n-3 series enrichment, but a stable LC-PUFAs n-6/n-3 ratio across age. BMI impact was analyzed by age subgroups to overcome the age effect. BMI increase is associated with LC-PUFAs n-6 accumulation, including arachidonic acid. Positive correlations between BMI and several LC-PUFAs n-6 were observed, as well as a strong imbalance in the LC-PUFAs n-6/n-3 ratio. Regarding cancer, axillary lymph nodes (p = 0.02) and inflammatory breast cancer (p = 0.08) are more frequently involved in obese women. Increased BMI induces an LC-PUFAs n-6 accumulation, including arachidonic acid, in adipose tissue. This may participate in the development of low-grade inflammation in obese women and breast tumor progression. These results suggest the value of lifestyle and LC-PUFAs n-3 potential, in the context of obesity and breast cancer secondary/tertiary prevention. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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17 pages, 2778 KiB  
Article
Anorexia Nervosa Is Associated with a Shift to Pro-Atherogenic Low-Density Lipoprotein Subclasses
by Julia T. Stadler, Sonja Lackner, Sabrina Mörkl, Nathalie Meier-Allard, Hubert Scharnagl, Alankrita Rani, Harald Mangge, Sieglinde Zelzer, Sandra J. Holasek and Gunther Marsche
Biomedicines 2022, 10(4), 895; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10040895 - 13 Apr 2022
Cited by 1 | Viewed by 3380
Abstract
Anorexia nervosa (AN) is a severe eating disorder affecting primarily female adolescents and younger adults. The energy deprivation associated with AN has been shown to alter lipoprotein metabolism, which may affect cardiovascular risk. However, the mechanisms leading to alterations in the composition, structure, [...] Read more.
Anorexia nervosa (AN) is a severe eating disorder affecting primarily female adolescents and younger adults. The energy deprivation associated with AN has been shown to alter lipoprotein metabolism, which may affect cardiovascular risk. However, the mechanisms leading to alterations in the composition, structure, and function of lipoproteins in AN patients are not well-understood yet. Here, we investigated the lipid abnormalities associated with AN, particularly changes in the distribution, composition, metabolism, and function of lipoprotein subclasses. In this exploratory study, we analyzed serum samples of 18 women diagnosed with AN (BMI < 17.5 kg/m2) and 24 normal-weight women (BMI from 18.5–24.9 kg/m2). Using the Quantimetrix Lipoprint® system, we determined low-density lipoprotein (LDL) subclass distribution, including quantitative measurements of very low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and high-density lipoprotein (HDL) subclass distribution. We quantified the most abundant apolipoproteins of HDL and assessed lecithin-cholesterol acyltransferase (LCAT) and cholesteryl-ester transfer protein (CETP) activities. In addition, anti-oxidative capacity of apoB-depleted serum and functional metrics of HDL, including cholesterol efflux capacity and paraoxonase activity were assessed. The atherogenic lipoprotein subclasses VLDL and small LDL particles were increased in AN. Levels of VLDL correlated significantly with CETP activity (rs = 0.432, p = 0.005). AN was accompanied by changes in the content of HDL-associated apolipoproteins involved in triglyceride catabolism, such as apolipoprotein C-II (+24%) and apoA-II (−27%), whereas HDL-associated cholesterol, phospholipids, and triglycerides were not altered. Moreover, AN did not affect HDL subclass distribution, cholesterol efflux capacity, and paraoxonase activity. We observed a shift to more atherogenic lipoprotein subclasses in AN patients, whereas HDL functionality and subclass distribution were not altered. This finding underpins potential detrimental effects of AN on lipid metabolism and the cardiovascular system by increasing atherosclerotic risk factors. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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16 pages, 5666 KiB  
Article
LSEA Evaluation of Lipid Mediators of Inflammation in Lung and Cortex of Mice Exposed to Diesel Air Pollution
by Luca Massimino, Alessandra Bulbarelli, Paola Antonia Corsetto, Chiara Milani, Laura Botto, Francesca Farina, Luigi Antonio Lamparelli, Elena Lonati, Federica Ungaro, Krishna Rao Maddipati, Paola Palestini and Angela Maria Rizzo
Biomedicines 2022, 10(3), 712; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10030712 - 19 Mar 2022
Cited by 1 | Viewed by 2361
Abstract
Airborne ultrafine particle (UFP) exposure is a great concern as they have been correlated to increased cardiovascular mortality, neurodegenerative diseases and morbidity in occupational and environmental settings. The ultrafine components of diesel exhaust particles (DEPs) represent about 25% of the emission mass; these [...] Read more.
Airborne ultrafine particle (UFP) exposure is a great concern as they have been correlated to increased cardiovascular mortality, neurodegenerative diseases and morbidity in occupational and environmental settings. The ultrafine components of diesel exhaust particles (DEPs) represent about 25% of the emission mass; these particles have a great surface area and consequently high capacity to adsorb toxic molecules, then transported throughout the body. Previous in-vivo studies indicated that DEP exposure increases pro- and antioxidant protein levels and activates inflammatory response both in respiratory and cardiovascular systems. In cells, DEPs can cause additional reactive oxygen species (ROS) production, which attacks surrounding molecules, such as lipids. The cell membrane provides lipid mediators (LMs) that modulate cell-cell communication, inflammation, and resolution processes, suggesting the importance of understanding lipid modifications induced by DEPs. In this study, with a lipidomic approach, we evaluated in the mouse lung and cortex how DEP acute and subacute treatments impact polyunsaturated fatty acid-derived LMs. To analyze the data, we designed an ad hoc bioinformatic pipeline to evaluate the functional enrichment of lipid sets belonging to the specific biological processes (Lipid Set Enrichment Analysis-LSEA). Moreover, the data obtained correlate tissue LMs and proteins associated with inflammatory process (COX-2, MPO), oxidative stress (HO-1, iNOS, and Hsp70), involved in the activation of many xenobiotics as well as PAH metabolism (Cyp1B1), suggesting a crucial role of lipids in the process of DEP-induced tissue damage. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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12 pages, 2403 KiB  
Article
PCOS: A Chronic Disease That Fails to Produce Adequately Specialized Pro-Resolving Lipid Mediators (SPMs)
by Pedro-Antonio Regidor, Xavier de la Rosa, Anna Müller, Manuela Mayr, Fernando Gonzalez Santos, Rafael Gracia Banzo and Jose Miguel Rizo
Biomedicines 2022, 10(2), 456; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10020456 - 16 Feb 2022
Cited by 7 | Viewed by 2480
Abstract
Introduction: Polycystic ovary syndrome (PCOS) is an endocrinological disorder that affects 5–15% of women of their reproductive age and is a frequent cause of infertility. Major symptoms include hyperandrogenism, ovulatory dysfunction, and often obesity and/or insulin resistance. PCOS also represents a state of [...] Read more.
Introduction: Polycystic ovary syndrome (PCOS) is an endocrinological disorder that affects 5–15% of women of their reproductive age and is a frequent cause of infertility. Major symptoms include hyperandrogenism, ovulatory dysfunction, and often obesity and/or insulin resistance. PCOS also represents a state of chronic low-grade inflammation that is closely interlinked with the metabolic features. “Classical” pro-inflammatory lipid mediators such as prostaglandins (PG), leukotrienes (LT), or thromboxanes (TX) are derived from arachidonic acid (AA) and are crucial for the initial response. Resolution processes are driven by four families of so-called specialized pro-resolving mediators (SPMs): resolvins, maresins, lipoxins, and protectins. The study aimed to establish lipid mediator profiles of PCOS patients compared to healthy women to identify differences in their resolutive and pro-inflammatory lipid parameters. Material and Methods: Fifteen female patients (18–45 years) were diagnosed with PCOS according to Rotterdam criteria, and five healthy women, as a comparator group, were recruited for the study. The main outcome measures were: pro-inflammatory lipid mediators (PG, LT, TX) and their precursor AA, SPMs (resolvins, maresins, protectins, lipoxins), their precursors EPA, DHA, DPA, and their active biosynthesis pathway intermediates (18-HEPE, 17-HDHA, 14-HDHA). Results: The level of pro-inflammatory parameters in serum was significantly higher in PCOS-affected women. The ratio (sum of pro-inflammatory molecules)/(sum of SPMs plus hydroxylated intermediates) reflecting the inflammatory state was significantly lower in the group of healthy women. Conclusion: There is a strong pro-inflammatory state in PCOS patients. Further research will clarify whether supplementation with SPMs or their precursors may improve this state. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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14 pages, 1968 KiB  
Article
The Differential Effects of HDL Subpopulations on Lipoprotein Lipase (LPL)-Mediated VLDL Catabolism
by Ewa Wieczorek, Agnieszka Ćwiklińska, Agnieszka Kuchta, Barbara Kortas-Stempak, Anna Gliwińska and Maciej Jankowski
Biomedicines 2021, 9(12), 1839; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9121839 - 05 Dec 2021
Cited by 8 | Viewed by 2197
Abstract
High-density lipoprotein (HDL) subpopulations functional assessment is more relevant for HDL anti-atherogenic activity than cholesterol level. The aim of the study was to assess the impact of HDL-2 and HDL-3 on lipoprotein lipase (LPL)-mediated very-low-density lipoprotein (VLDL) catabolism related to hypertriglyceridemia development. VLDL [...] Read more.
High-density lipoprotein (HDL) subpopulations functional assessment is more relevant for HDL anti-atherogenic activity than cholesterol level. The aim of the study was to assess the impact of HDL-2 and HDL-3 on lipoprotein lipase (LPL)-mediated very-low-density lipoprotein (VLDL) catabolism related to hypertriglyceridemia development. VLDL and HDLs were isolated from serum by ultracentrifugation. VLDL was incubated with LPL in the absence and presence of total HDL or HDL subpopulations. Next, VLDL remnants were separated, and their composition and electrophoretic mobility was assessed. Both HDL subpopulations increased the efficiency of triglyceride lipolysis and apolipoprotein CII and CIII removal from VLDL up to ~90%. HDL-3 exerted significantly greater impact than HDL-2 on apolipoprotein E (43% vs. 18%, p < 0.001), free cholesterol (26% vs. 18%, p < 0.05) and phospholipids (53% vs. 43%, p < 0.05) removal from VLDL and VLDL remnant electrophoretic mobility (0.18 vs. 0.20, p < 0.01). A greater release of these components was also observed in the presence of total HDL with a low HDL-2/HDL-3 cholesterol ratio. Both HDL subpopulations affect VLDL composition during lipolysis, but HDL-3 exhibited a greater effect on this process. Altered composition of HDL related to significant changes in the distribution between HDL-2 and HDL-3 can influence the VLDL remnant features, affecting atherosclerosis progression. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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Review

Jump to: Research

13 pages, 999 KiB  
Review
Lipid Nanoparticles and Liposomes for Bone Diseases Treatment
by Alexandra-Cristina Burdușel and Ecaterina Andronescu
Biomedicines 2022, 10(12), 3158; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10123158 - 07 Dec 2022
Cited by 6 | Viewed by 1793
Abstract
Because of their outstanding biocompatibility, sufficient capacity to control drug release, and passive targeting capability, lipid nanoparticles are one of the world’s most widely utilized drug delivery systems. However, numerous disadvantages limit the use of lipid nanoparticles in clinical settings, especially in bone [...] Read more.
Because of their outstanding biocompatibility, sufficient capacity to control drug release, and passive targeting capability, lipid nanoparticles are one of the world’s most widely utilized drug delivery systems. However, numerous disadvantages limit the use of lipid nanoparticles in clinical settings, especially in bone regeneration, such as challenges in transporting, storing, and maintaining drug concentration in the local area. Scaffolds are frequently employed as implants to provide mechanical support to the damaged area or as diagnostic and imaging tools. On the other hand, unmodified scaffolds have limited powers in fostering tissue regeneration and curing illnesses. Liposomes offer a solid foundation for the long-term development of various commercial solutions for the effective drug delivery-assisted treatment of medical conditions. As drug delivery vehicles in medicine, adjuvants in vaccination, signal enhancers/carriers in medical diagnostics and analytical biochemistry, solubilizers for various ingredients as well as support matrices for various ingredients, and penetration enhancers in cosmetics are just a few of the industrial applications for liposomes. This review introduces and discusses the use of lipid nanoparticles and liposomes and the application of lipid nanoparticles and liposome systems based on different active substances in bone diseases. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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15 pages, 855 KiB  
Review
Start Me Up: How Can Surrounding Gangliosides Affect Sodium-Potassium ATPase Activity and Steer towards Pathological Ion Imbalance in Neurons?
by Borna Puljko, Mario Stojanović, Katarina Ilic, Svjetlana Kalanj-Bognar and Kristina Mlinac-Jerkovic
Biomedicines 2022, 10(7), 1518; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10071518 - 27 Jun 2022
Cited by 2 | Viewed by 2494
Abstract
Gangliosides, amphiphilic glycosphingolipids, tend to associate laterally with other membrane constituents and undergo extensive interactions with membrane proteins in cis or trans configurations. Studies of human diseases resulting from mutations in the ganglioside biosynthesis pathway and research on transgenic mice with the same [...] Read more.
Gangliosides, amphiphilic glycosphingolipids, tend to associate laterally with other membrane constituents and undergo extensive interactions with membrane proteins in cis or trans configurations. Studies of human diseases resulting from mutations in the ganglioside biosynthesis pathway and research on transgenic mice with the same mutations implicate gangliosides in the pathogenesis of epilepsy. Gangliosides are reported to affect the activity of the Na+/K+-ATPase, the ubiquitously expressed plasma membrane pump responsible for the stabilization of the resting membrane potential by hyperpolarization, firing up the action potential and ion homeostasis. Impaired Na+/K+-ATPase activity has also been hypothesized to cause seizures by several mechanisms. In this review we present different epileptic phenotypes that are caused by impaired activity of Na+/K+-ATPase or changed membrane ganglioside composition. We further discuss how gangliosides may influence Na+/K+-ATPase activity by acting as lipid sorting machinery providing the optimal stage for Na+/K+-ATPase function. By establishing a distinct lipid environment, together with other membrane lipids, gangliosides possibly modulate Na+/K+-ATPase activity and aid in “starting up” and “turning off” this vital pump. Therefore, structural changes of neuronal membranes caused by altered ganglioside composition can be a contributing factor leading to aberrant Na+/K+-ATPase activity and ion imbalance priming neurons for pathological firing. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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18 pages, 1271 KiB  
Review
A Potential Interplay between HDLs and Adiponectin in Promoting Endothelial Dysfunction in Obesity
by Monica Zocchi, Matteo Della Porta, Federico Lombardoni, Roberta Scrimieri, Gian Vincenzo Zuccotti, Jeanette A. Maier and Roberta Cazzola
Biomedicines 2022, 10(6), 1344; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10061344 - 07 Jun 2022
Cited by 6 | Viewed by 2702
Abstract
Obesity is an epidemic public health problem that has progressively worsened in recent decades and is associated with low-grade chronic inflammation (LGCI) in metabolic tissues and an increased risk of several diseases. In particular, LGCI alters metabolism and increases cardiovascular risk by impairing [...] Read more.
Obesity is an epidemic public health problem that has progressively worsened in recent decades and is associated with low-grade chronic inflammation (LGCI) in metabolic tissues and an increased risk of several diseases. In particular, LGCI alters metabolism and increases cardiovascular risk by impairing endothelial function and altering the functions of adiponectin and high-density lipoproteins (HDLs). Adiponectin is an adipokine involved in regulating energy metabolism and body composition. Serum adiponectin levels are reduced in obese individuals and negatively correlate with chronic sub-clinical inflammatory markers. HDLs are a heterogeneous and complex class of lipoproteins that can be dysfunctional in obesity. Adiponectin and HDLs are strictly interdependent, and the maintenance of their interplay is essential for vascular function. Since such a complex network of interactions is still overlooked in clinical settings, this review aims to highlight the mechanisms involved in the impairment of the HDLs/adiponectin axis in obese patients to predict the risk of cardiovascular diseases and activate preventive countermeasures. Here, we provide a narrative review of the role of LGCI in altering HDLs, adiponectin and endothelial functions in obesity to encourage new studies about their synergic effects on cardiovascular health and disease. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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18 pages, 2934 KiB  
Review
Phospholipid Membrane Transport and Associated Diseases
by Raúl Ventura, Inma Martínez-Ruiz and María Isabel Hernández-Alvarez
Biomedicines 2022, 10(5), 1201; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051201 - 23 May 2022
Cited by 10 | Viewed by 4282
Abstract
Phospholipids are the basic structure block of eukaryotic membranes, in both the outer and inner membranes, which delimit cell organelles. Phospholipids can also be damaged by oxidative stress produced by mitochondria, for instance, becoming oxidized phospholipids. These damaged phospholipids have been related to [...] Read more.
Phospholipids are the basic structure block of eukaryotic membranes, in both the outer and inner membranes, which delimit cell organelles. Phospholipids can also be damaged by oxidative stress produced by mitochondria, for instance, becoming oxidized phospholipids. These damaged phospholipids have been related to prevalent diseases such as atherosclerosis or non-alcoholic steatohepatitis (NASH) because they alter gene expression and induce cellular stress and apoptosis. One of the main sites of phospholipid synthesis is the endoplasmic reticulum (ER). ER association with other organelles through membrane contact sites (MCS) provides a close apposition for lipid transport. Additionally, an important advance in this small cytosolic gap are lipid transfer proteins (LTPs), which accelerate and modulate the distribution of phospholipids in other organelles. In this regard, LTPs can be established as an essential point within phospholipid circulation, as relevant data show impaired phospholipid transport when LTPs are defected. This review will focus on phospholipid function, metabolism, non-vesicular transport, and associated diseases. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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14 pages, 1948 KiB  
Review
Premenopausal Syndrome and NAFLD: A New Approach Based on Gender Medicine
by Livianna Carrieri, Alberto Ruben Osella, Fausto Ciccacci, Gianluigi Giannelli and Maria Principia Scavo
Biomedicines 2022, 10(5), 1184; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051184 - 20 May 2022
Cited by 3 | Viewed by 2056
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition that affects 25% of the world’s population. There is a clear difference in both geographical distribution and sex in childbearing age. These differences are reduced when women become older and senescence begins. The factors [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition that affects 25% of the world’s population. There is a clear difference in both geographical distribution and sex in childbearing age. These differences are reduced when women become older and senescence begins. The factors that affect the likelihood of developing NAFLD in a premenopausal woman are an imbalance of sex hormones (especially in estradiol and androgen), microbiome dysregulation, insulin resistance, early menarche, the length of time that the woman breastfeeds for and polycystic ovarian syndrome (PCOS). The aim of this review is to identify various physical ailments that may not appear to be serious to young women but that then affect the onset of NAFLD in perimenopause and can degenerate into NASH. These conditions should also be considered in future clinical management, as well as in research opportunities, in order to customize the monitoring and treatment of NAFLD, considering gender medicine for those women who had early metabolic symptoms that were not considered to be significant at the time. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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23 pages, 1287 KiB  
Review
Lipid Metabolic Alterations in the ALS–FTD Spectrum of Disorders
by Juan Miguel Godoy-Corchuelo, Luis C. Fernández-Beltrán, Zeinab Ali, María J. Gil-Moreno, Juan I. López-Carbonero, Antonio Guerrero-Sola, Angélica Larrad-Sainz, Jorge Matias-Guiu, Jordi A. Matias-Guiu, Thomas J. Cunningham and Silvia Corrochano
Biomedicines 2022, 10(5), 1105; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051105 - 10 May 2022
Cited by 11 | Viewed by 3292
Abstract
There is an increasing interest in the study of the relation between alterations in systemic lipid metabolism and neurodegenerative disorders, in particular in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). In ALS these alterations are well described and evident not only with [...] Read more.
There is an increasing interest in the study of the relation between alterations in systemic lipid metabolism and neurodegenerative disorders, in particular in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). In ALS these alterations are well described and evident not only with the progression of the disease but also years before diagnosis. Still, there are some discrepancies in findings relating to the causal nature of lipid metabolic alterations, partly due to the great clinical heterogeneity in ALS. ALS presentation is within a disorder spectrum with Frontotemporal Dementia (FTD), and many patients present mixed forms of ALS and FTD, thus increasing the variability. Lipid metabolic and other systemic metabolic alterations have not been well studied in FTD, or in ALS–FTD mixed forms, as has been in pure ALS. With the recent development in lipidomics and the integration with other -omics platforms, there is now emerging data that not only facilitates the identification of biomarkers but also enables understanding of the underlying pathological mechanisms. Here, we reviewed the recent literature to compile lipid metabolic alterations in ALS, FTD, and intermediate mixed forms, with a view to appraising key commonalities or differences within the spectrum. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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Graphical abstract

18 pages, 2800 KiB  
Review
Targeted Strategy in Lipid-Lowering Therapy
by Ezgi Dayar and Olga Pechanova
Biomedicines 2022, 10(5), 1090; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051090 - 08 May 2022
Cited by 19 | Viewed by 7477
Abstract
Dyslipidemia is characterized by a diminished lipid profile, including increased level of total cholesterol and low-density lipoprotein cholesterol (LDL-c) and reduced level of high-density lipoprotein cholesterol (HDL-c). Lipid-lowering agents represent an efficient tool for the prevention or reduction of progression of atherosclerosis, coronary [...] Read more.
Dyslipidemia is characterized by a diminished lipid profile, including increased level of total cholesterol and low-density lipoprotein cholesterol (LDL-c) and reduced level of high-density lipoprotein cholesterol (HDL-c). Lipid-lowering agents represent an efficient tool for the prevention or reduction of progression of atherosclerosis, coronary heart diseases and metabolic syndrome. Statins, ezetimibe, and recently proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are the most effective and used drugs in clinical lipid-lowering therapy. These drugs are mainly aimed to lower cholesterol levels by different mechanisms of actions. Statins, the agents of the first-line therapy—known as 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors—suppress the liver cholesterol synthesis. Ezetimibe as the second-line therapy can decrease cholesterol by inhibiting cholesterol absorption. Finally, the PCSK9 inhibitors act as an inducer of LDL excretion. In spite of their beneficial lipid-lowering properties, many patients suffer from their serious side effects, route of administration, or unsatisfactory physicochemical characteristics. Clinical demand for dose reduction and the improvement of bioavailability as well as pharmacodynamic and pharmacokinetic profile has resulted in the development of a new targeted therapy that includes nanoparticle carriers, emulsions or vaccination often associated with another more subtle form of administration. Targeted therapy aims to exert a more potent drug profile with lipid-lowering properties either alone or in mutual combination to potentiate their beneficial effects. This review describes the most effective lipid-lowering drugs, their favorable and adverse effects, as well as targeted therapy and alternative treatments to help reduce or prevent atherosclerotic processes and cardiovascular events. Full article
(This article belongs to the Special Issue The Lipid Metabolism in Health and Diseases)
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