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Lipids: From the Structure, Function and Evolution to Applications

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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 2022) | Viewed by 87150

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Special Issue Editors

Prof. Dr. Debbie C. Crans

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Department of Chemistry, Colorado State University, Fort Colllins, CO 80523, USA
Interests: metals in medicine; vanadium; drugs and biologically active compounds; cancer; diabetes; tuberculosis; pharmaceutically active compounds; transition metals; platinum, ruthenium, copper, rhenium, lipid and lipid model interfaces; hydrophobic compounds; spectroscopy; reverse micelles; chemistry in confined spaces
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Dr. Tom Santangelo

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Biochemistry and Molecular Biology Department, Colorado State University, Fort Collins, CO 80523, USA
Interests: molecular microbiology; genetics and physiology; transcription regulation; DNA replication and repair

Special Issue Information

Dear Colleagues,

Lipidomics is an emerging field of foundational and biomedical research that includes the study of naturally diverse and synthetic lipid biosynthetic pathways, mechanisms to identify and quantify changes to lipid profiles at the cellular and organismal levels, and efforts to leverage distinct lipids for biotechnological approaches. The complex stereochemistry of many lipids and their inherently polar nature often complicate chemical syntheses and isolations, and the radical differences between archaeal and bacterial/eukaryotic lipids provide additional challenges and potential. Diversity in lipid structure is a welcome topic given that archaeal lipids are built on a glycerol-1-phosphate backbone and contain ether-linked isoprenoid chains, while bacterial and eukaryotic lipids are composed of a fatty acid ester linked to a glycerol-3-phosphate. Details on the biological function of distinct lipids, the evolutionary lipid divide, the location(s) and synthesis of unique lipids, including derivation and tetraether monolayers, and the role lipids can play in medicinal settings are of interest. Topics focused on technical advances in areas such as microbiology, mass spectrometry, chemistry, biochemistry, and imaging with respect to lipids are also encouraged. This Special Issue is focused on fundamental studies of diverse lipids as well as their properties and function in biochemical, biological, and medicinal systems.

Potential topics include, but are not limited to, the following:

Synthesis, isolation, and quantification of natural lipids and lipid derivatives (triglycerides, phospholipids, cholesterol, inositol, fatty acids, second messengers, archaeal lipids, and analogs);
The evolutionary lipid divide (isoprenoids and retention of lipid biosynthetic pathways in diverse clades, inclusive of redundant or novel pathways for lipid biosynthesis);
New technologies to explore the biological, physical, structural, and chemical features of lipids and lipid assemblies, including mixed systems;
Identification and characterization of proteins and enzymes that synthesize, bind, and process lipids;
Lipid membrane composition, fluidity, properties, and rafting;
The importance and application of lipids in health and disease;
Dynamic changes to lipids in environmental extremes.

Prof. Dr. Debbie C. Crans
Dr. Tom Santangelo
Guest Editors

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Published Papers (13 papers)

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Research

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16 pages, 8466 KiB

Open AccessArticle

Membrane Adaptations and Cellular Responses of Sulfolobus acidocaldarius to the Allylamine Terbinafine

by Alka Rao, Niels A. W. de Kok and Arnold J. M. Driessen

Int. J. Mol. Sci. 2023, 24(8), 7328; https://doi.org/10.3390/ijms24087328 - 15 Apr 2023

Cited by 3 | Viewed by 3686

Abstract

Cellular membranes are essential for compartmentalization, maintenance of permeability, and fluidity in all three domains of life. Archaea belong to the third domain of life and have a distinct phospholipid composition. Membrane lipids of archaea are ether-linked molecules, specifically bilayer-forming dialkyl glycerol diethers (DGDs) and monolayer-forming glycerol dialkyl glycerol tetraethers (GDGTs). The antifungal allylamine terbinafine has been proposed as an inhibitor of GDGT biosynthesis in archaea based on radiolabel incorporation studies. The exact target(s) and mechanism of action of terbinafine in archaea remain elusive. Sulfolobus acidocaldarius is a strictly aerobic crenarchaeon thriving in a thermoacidophilic environment, and its membrane is dominated by GDGTs. Here, we comprehensively analyzed the lipidome and transcriptome of S. acidocaldarius in the presence of terbinafine. Depletion of GDGTs and the accompanying accumulation of DGDs upon treatment with terbinafine were growth phase-dependent. Additionally, a major shift in the saturation of caldariellaquinones was observed, which resulted in the accumulation of unsaturated molecules. Transcriptomic data indicated that terbinafine has a multitude of effects, including significant differential expression of genes in the respiratory complex, motility, cell envelope, fatty acid metabolism, and GDGT cyclization. Combined, these findings suggest that the response of S. acidocaldarius to terbinafine inhibition involves respiratory stress and the differential expression of genes involved in isoprenoid biosynthesis and saturation. Full article

(This article belongs to the Special Issue Lipids: From the Structure, Function and Evolution to Applications)

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18 pages, 3900 KiB

Open AccessArticle

Transmembrane Protein 68 Functions as an MGAT and DGAT Enzyme for Triacylglycerol Biosynthesis

by Yu Wang, Fansi Zeng, Zheng Zhao, Lin He, Xiaohong He, Huimin Pang, Feifei Huang and Pingan Chang

Int. J. Mol. Sci. 2023, 24(3), 2012; https://doi.org/10.3390/ijms24032012 - 19 Jan 2023

Cited by 9 | Viewed by 3337

Abstract

Triacylglycerol (TG) biosynthesis is an important metabolic process for intracellular storage of surplus energy, intestinal dietary fat absorption, attenuation of lipotoxicity, lipid transportation, lactation and signal transduction in mammals. Transmembrane protein 68 (TMEM68) is an endoplasmic reticulum (ER)-anchored acyltransferase family member of unknown function. In the current study we show that overexpression of TMEM68 promotes TG accumulation and lipid droplet (LD) formation in a conserved active sites-dependent manner. Quantitative targeted lipidomic analysis showed that diacylglycerol (DG), free fatty acid (FFA) and TG levels were increased by TMEM68 expression. In addition, TMEM68 overexpression affected the levels of several glycerophospholipids, such as phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, as well as sterol ester contents. TMEM68 exhibited monoacylglycerol acyltransferase (MGAT) and diacylglycerol acyltransferase (DGAT) activities dependent on the conserved active sites in an in vitro assay. The expression of lipogenesis genes, including DGATs, fatty acid synthesis-related genes and peroxisome proliferator-activated receptor γ was upregulated in TMEM68-overexpressing cells. These results together demonstrate for the first time that TMEM68 functions as an acyltransferase and affects lipogenic gene expression, glycerolipid metabolism and TG storage in mammalian cells. Full article

(This article belongs to the Special Issue Lipids: From the Structure, Function and Evolution to Applications)

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19 pages, 3486 KiB

Open AccessArticle

RNA-Seq Analysis Identifies Differentially Expressed Genes in the Longissimus dorsi of Wagyu and Chinese Red Steppe Cattle

by Guanghui Li, Runjun Yang, Xin Lu, Yue Liu, Wei He, Yue Li, Haibin Yu, Lihong Qin, Yang Cao, Zhihui Zhao and Xibi Fang

Int. J. Mol. Sci. 2023, 24(1), 387; https://doi.org/10.3390/ijms24010387 - 26 Dec 2022

Cited by 25 | Viewed by 4074

Abstract

Meat quality has a close relationship with fat and connective tissue; therefore, screening and identifying functional genes related to lipid metabolism is essential for the production of high-grade beef. The transcriptomes of the Longissimus dorsi muscle in Wagyu and Chinese Red Steppe cattle, breeds with significant differences in meat quality and intramuscular fat deposition, were analyzed using RNA-seq to screen for candidate genes associated with beef quality traits. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the 388 differentially expressed genes (DEGs) were involved in biological processes such as short-chain fatty acid metabolism, regulation of fatty acid transport and the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In addition, crystallin alpha B (CRYAB), ankyrin repeat domain 2 (ANKRD2), aldehyde dehydrogenase 9 family member A1 (ALDH9A1) and enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH) were investigated for their effects on intracellular triglyceride and fatty acid content and their regulatory effects on genes in lipogenesis and fatty acid metabolism pathways. This study generated a dataset from transcriptome profiling of two cattle breeds, with differing capacities for fat-deposition in the muscle, and revealed molecular evidence that CRYAB, ANKRD2, ALDH9A1 and EHHADH are related to fat metabolism in bovine fetal fibroblasts (BFFs). The results provide potential functional genes for maker-assisted selection and molecular breeding to improve meat quality traits in beef cattle. Full article

(This article belongs to the Special Issue Lipids: From the Structure, Function and Evolution to Applications)

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20 pages, 3223 KiB

Open AccessArticle

The Influence of Acitretin on Brain Lipidomics in Adolescent Mice—Implications for Pediatric and Adolescent Dermatological Therapy

by Anna A. Lauer, Vu Thu Thuy Nguyen, Daniel Janitschke, Malena dos Santos Guilherme, Cornel M. Bachmann, Heike S. Grimm, Tobias Hartmann, Kristina Endres and Marcus O. W. Grimm

Int. J. Mol. Sci. 2022, 23(24), 15535; https://doi.org/10.3390/ijms232415535 - 8 Dec 2022

Cited by 2 | Viewed by 2176

Abstract

Administration of systemic retinoids such as acitretin has not been approved yet for pediatric patients. An adverse event of retinoid-therapy that occurs with lower prevalence in children than in adults is hyperlipidemia. This might be based on the lack of comorbidities in young patients, but must not be neglected. Especially for the development of the human brain up to young adulthood, dysbalance of lipids might be deleterious. Here, we provide for the first time an in-depth analysis of the influence of subchronic acitretin-administration on lipid composition of brain parenchyma of young wild type mice. For comparison and to evaluate the systemic effect of the treatment, liver lipids were analogously investigated. As expected, triglycerides increased in liver as well as in brain and a non-significant increase in cholesterol was observed. However, specifically brain showed an increase in lyso-phosphatidylcholine and carnitine as well as in sphingomyelin. Group analysis of lipid classes revealed no statistical effects, while single species were tissue-dependently changed: effects in brain were in general more subtly as compared to those in liver regarding the mere number of changed lipid species. Thus, while the overall impact of acitretin seems comparably small regarding brain, the change in individual species and their role in brain development and maturation has to be considered. Full article

(This article belongs to the Special Issue Lipids: From the Structure, Function and Evolution to Applications)

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19 pages, 1340 KiB

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Norepinephrine Inhibits Lipopolysaccharide-Stimulated TNF-α but Not Oxylipin Induction in n-3/n-6 PUFA-Enriched Cultures of Circumventricular Organs

by Fabian Johannes Pflieger, Jacqueline Wolf, Martin Feldotto, Andreas Nockher, Tatjana Wenderoth, Jessica Hernandez, Joachim Roth, Daniela Ott and Christoph Rummel

Int. J. Mol. Sci. 2022, 23(15), 8745; https://doi.org/10.3390/ijms23158745 - 6 Aug 2022

Cited by 2 | Viewed by 2785

Abstract

Sensory circumventricular organs (sCVOs) are pivotal brain structures involved in immune-to-brain communication with a leaky blood–brain barrier that detect circulating mediators such as lipopolysaccharide (LPS). Here, we aimed to investigate the potential of sCVOs to produce n-3 and n-6 oxylipins after LPS-stimulation. Moreover, we investigated if norepinephrine (NE) co-treatment can alter cytokine- and oxylipin-release. Thus, we stimulated rat primary neuroglial sCVO cultures under n-3- or n-6-enriched conditions with LPS or saline combined with NE or vehicle. Supernatants were assessed for cytokines by bioassays and oxylipins by HPLC-MS/MS. Expression of signaling pathways and enzymes were analyzed by RT-PCR. Tumor necrosis factor (TNF)α bioactivity and signaling, IL-10 expression, and cyclooxygenase (COX)2 were increased, epoxide hydroxylase (Ephx)2 was reduced, and lipoxygenase 15-(LOX) was not changed by LPS stimulation. Moreover, LPS induced increased levels of several n-6-derived oxylipins, including the COX-2 metabolite 15d-prostaglandin-J2 or the Ephx2 metabolite 14,15-DHET. For n-3-derived oxylipins, some were down- and some were upregulated, including 15-LOX-derived neuroprotectin D1 and 18-HEPE, known for their anti-inflammatory potential. While the LPS-induced increase in TNFα levels was significantly reduced by NE, oxylipins were not significantly altered by NE or changes in TNFα levels. In conclusion, LPS-induced oxylipins may play an important functional role in sCVOs for immune-to-brain communication. Full article

(This article belongs to the Special Issue Lipids: From the Structure, Function and Evolution to Applications)

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16 pages, 4249 KiB

Open AccessArticle

Differential Inflammatory Responses in Cultured Endothelial Cells Exposed to Two Conjugated Linoleic Acids (CLAs) under a Pro-Inflammatory Condition

by Carina A. Valenzuela, Ella J. Baker, Elizabeth A. Miles and Philip C. Calder

Int. J. Mol. Sci. 2022, 23(11), 6101; https://doi.org/10.3390/ijms23116101 - 29 May 2022

Cited by 3 | Viewed by 2331

Abstract

Conjugated linoleic acid (CLA) isomers have been shown to possess anti-atherosclerotic properties, which may be related to the downregulation of inflammatory pathways in different cell types, including endothelial cells (ECs). However, whether different CLA isomers have different actions is not entirely clear, with inconsistent reports to date. Furthermore, in cell culture studies, CLAs have often been used at fairly high concentrations. Whether lower concentrations of CLAs are able to affect EC responses is not clear. The aim of this study was to evaluate the effects of two CLAs (cis-9, trans-11 (CLA9,11) and trans-10, cis-12 (CLA10,12)) on the inflammatory responses of ECs. ECs (EA.hy926 cells) were cultured under standard conditions and exposed to CLAs (1 to 50 μM) for 48 h. Then, the cells were cultured for a further 6 or 24 h with tumour necrosis factor alpha (TNF-α, 1 ng/mL) as an inflammatory stimulant. ECs remained viable after treatments with 1 and 10 μM of each CLA, but not after treatment with 50 μM of CLA10,12. CLAs were incorporated into ECs in a concentration-dependent manner. CLA10,12 increased the levels of ICAM-1, IL-6, and RANTES in the culture medium, while CLA9,11 had null effects. Both CLAs (1 μM) decreased the appearance of NFκB1 mRNA, but only CLA9,11 maintained this downregulation at 10 μM. CLA10,12 had no effect on THP-1 cell adhesion to ECs while significantly decreasing the percentage of ECs expressing ICAM-1 and also levels of ICAM-1 expression per cell when used at 10 µM. Although CLA9,11 did not have any effect on ICAM-1 cell surface expression, it reduced THP-1 cell adhesion to the EA.hy926 cell monolayer at both concentrations. In summary, CLA10,12 showed some pro-inflammatory effects, while CLA9,11 exhibited null or anti-inflammatory effects. The results suggest that each CLA has different effects in ECs under a pro-inflammatory condition, highlighting the need to evaluate the effects of CLA isomers independently. Full article

(This article belongs to the Special Issue Lipids: From the Structure, Function and Evolution to Applications)

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25 pages, 3520 KiB

Open AccessArticle

Order vs. Disorder: Cholesterol and Omega-3 Phospholipids Determine Biomembrane Organization

by Augusta de Santis, Ernesto Scoppola, Maria Francesca Ottaviani, Alexandros Koutsioubas, Lester C. Barnsley, Luigi Paduano, Gerardino D’Errico and Irene Russo Krauss

Int. J. Mol. Sci. 2022, 23(10), 5322; https://doi.org/10.3390/ijms23105322 - 10 May 2022

Cited by 10 | Viewed by 2683

Abstract

Lipid structural diversity strongly affects biomembrane chemico-physical and structural properties in addition to membrane-associated events. At high concentrations, cholesterol increases membrane order and rigidity, while polyunsaturated lipids are reported to increase disorder and flexibility. How these different tendencies balance in composite bilayers is still controversial. In this study, electron paramagnetic resonance spectroscopy, small angle neutron scattering, and neutron reflectivity were used to investigate the structural properties of cholesterol-containing lipid bilayers in the fluid state with increasing amounts of polyunsaturated omega-3 lipids. Either the hybrid 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine or the symmetric 1,2-docosahexaenoyl-sn-glycero-3-phosphocholine were added to the mixture of the naturally abundant 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine and cholesterol. Our results indicate that the hybrid and the symmetric omega-3 phospholipids affect the microscopic organization of lipid bilayers differently. Cholesterol does not segregate from polyunsaturated phospholipids and, through interactions with them, is able to suppress the formation of non-lamellar structures induced by the symmetric polyunsaturated lipid. However, this order/disorder balance leads to a bilayer whose structural organization cannot be ascribed to either a liquid ordered or to a canonical liquid disordered phase, in that it displays a very loose packing of the intermediate segments of lipid chains. Full article

(This article belongs to the Special Issue Lipids: From the Structure, Function and Evolution to Applications)

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Review

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50 pages, 2536 KiB

Open AccessReview

Rhamnolipid Self-Aggregation in Aqueous Media: A Long Journey toward the Definition of Structure–Property Relationships

by Rodolfo Esposito, Immacolata Speciale, Cristina De Castro, Gerardino D’Errico and Irene Russo Krauss

Int. J. Mol. Sci. 2023, 24(6), 5395; https://doi.org/10.3390/ijms24065395 - 11 Mar 2023

Cited by 30 | Viewed by 3694

Abstract

The need to protect human and environmental health and avoid the widespread use of substances obtained from nonrenewable sources is steering research toward the discovery and development of new molecules characterized by high biocompatibility and biodegradability. Due to their very widespread use, a class of substances for which this need is particularly urgent is that of surfactants. In this respect, an attractive and promising alternative to commonly used synthetic surfactants is represented by so-called biosurfactants, amphiphiles naturally derived from microorganisms. One of the best-known families of biosurfactants is that of rhamnolipids, which are glycolipids with a headgroup formed by one or two rhamnose units. Great scientific and technological effort has been devoted to optimization of their production processes, as well as their physicochemical characterization. However, a conclusive structure–function relationship is far from being defined. In this review, we aim to move a step forward in this direction, by presenting a comprehensive and unified discussion of physicochemical properties of rhamnolipids as a function of solution conditions and rhamnolipid structure. We also discuss still unresolved issues that deserve further investigation in the future, to allow the replacement of conventional surfactants with rhamnolipids. Full article

(This article belongs to the Special Issue Lipids: From the Structure, Function and Evolution to Applications)

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39 pages, 5334 KiB

Open AccessReview

Biological Consequences of Vanadium Effects on Formation of Reactive Oxygen Species and Lipid Peroxidation

by Manuel Aureliano, Ana Luísa De Sousa-Coelho, Connor C. Dolan, Deborah A. Roess and Debbie C. Crans

Int. J. Mol. Sci. 2023, 24(6), 5382; https://doi.org/10.3390/ijms24065382 - 11 Mar 2023

Cited by 72 | Viewed by 4834

Abstract

Lipid peroxidation (LPO), a process that affects human health, can be induced by exposure to vanadium salts and compounds. LPO is often exacerbated by oxidation stress, with some forms of vanadium providing protective effects. The LPO reaction involves the oxidation of the alkene bonds, primarily in polyunsaturated fatty acids, in a chain reaction to form radical and reactive oxygen species (ROS). LPO reactions typically affect cellular membranes through direct effects on membrane structure and function as well as impacting other cellular functions due to increases in ROS. Although LPO effects on mitochondrial function have been studied in detail, other cellular components and organelles are affected. Because vanadium salts and complexes can induce ROS formation both directly and indirectly, the study of LPO arising from increased ROS should include investigations of both processes. This is made more challenging by the range of vanadium species that exist under physiological conditions and the diverse effects of these species. Thus, complex vanadium chemistry requires speciation studies of vanadium to evaluate the direct and indirect effects of the various species that are present during vanadium exposure. Undoubtedly, speciation is important in assessing how vanadium exerts effects in biological systems and is likely the underlying cause for some of the beneficial effects reported in cancerous, diabetic, neurodegenerative conditions and other diseased tissues impacted by LPO processes. Speciation of vanadium, together with investigations of ROS and LPO, should be considered in future biological studies evaluating vanadium effects on the formation of ROS and on LPO in cells, tissues, and organisms as discussed in this review. Full article

(This article belongs to the Special Issue Lipids: From the Structure, Function and Evolution to Applications)

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37 pages, 16168 KiB

Open AccessReview

Chemistry of Lipoquinones: Properties, Synthesis, and Membrane Location of Ubiquinones, Plastoquinones, and Menaquinones

by Margaret M. Braasch-Turi, Jordan T. Koehn and Debbie C. Crans

Int. J. Mol. Sci. 2022, 23(21), 12856; https://doi.org/10.3390/ijms232112856 - 25 Oct 2022

Cited by 10 | Viewed by 2834

Abstract

Lipoquinones are the topic of this review and are a class of hydrophobic lipid molecules with key biological functions that are linked to their structure, properties, and location within a biological membrane. Ubiquinones, plastoquinones, and menaquinones vary regarding their quinone headgroup, isoprenoid sidechain, properties, and biological functions, including the shuttling of electrons between membrane-bound protein complexes within the electron transport chain. Lipoquinones are highly hydrophobic molecules that are soluble in organic solvents and insoluble in aqueous solution, causing obstacles in water-based assays that measure their chemical properties, enzyme activities and effects on cell growth. Little is known about the location and ultimately movement of lipoquinones in the membrane, and these properties are topics described in this review. Computational studies are particularly abundant in the recent years in this area, and there is far less experimental evidence to verify the often conflicting interpretations and conclusions that result from computational studies of very different membrane model systems. Some recent experimental studies have described using truncated lipoquinone derivatives, such as ubiquinone-2 (UQ-2) and menaquinone-2 (MK-2), to investigate their conformation, their location in the membrane, and their biological function. Truncated lipoquinone derivatives are soluble in water-based assays, and hence can serve as excellent analogs for study even though they are more mobile in the membrane than the longer chain counterparts. In this review, we will discuss the properties, location in the membrane, and syntheses of three main classes of lipoquinones including truncated derivatives. Our goal is to highlight the importance of bridging the gap between experimental and computational methods and to incorporate properties-focused considerations when proposing future studies relating to the function of lipoquinones in membranes. Full article

(This article belongs to the Special Issue Lipids: From the Structure, Function and Evolution to Applications)

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25 pages, 2970 KiB

Open AccessReview

Synthesis of C_20–38 Fatty Acids in Plant Tissues

by Anatoly Zhukov and Valery Popov

Int. J. Mol. Sci. 2022, 23(9), 4731; https://doi.org/10.3390/ijms23094731 - 25 Apr 2022

Cited by 15 | Viewed by 4131

Abstract

Very-long-chain fatty acids (VLCFA) are involved in a number of important plant physiological functions. Disorders in the expression of genes involved in the synthesis of VLCFA lead to a number of phenotypic consequences, ranging from growth retardation to the death of embryos. The elongation of VLCFA in the endoplasmic reticulum (ER) is carried out by multiple elongase complexes with different substrate specificities and adapted to the synthesis of a number of products required for a number of metabolic pathways. The information about the enzymes involved in the synthesis of VLCFA with more than 26 atoms of Carbon is rather poor. Recently, genes encoding enzymes involved in the synthesis of both regular-length fatty acids and VLCFA have been discovered and investigated. Polyunsaturated VLCFA in plants are formed mainly by 20:1 elongation into new monounsaturated acids, which are then imported into chloroplasts, where they are further desaturated. The formation of saturated VLCFA and their further transformation into a number of aliphatic compounds included in cuticular waxes and suberin require the coordinated activity of a large number of different enzymes. Full article

(This article belongs to the Special Issue Lipids: From the Structure, Function and Evolution to Applications)

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21 pages, 723 KiB

Open AccessReview

Emerging Evidence of Pathological Roles of Very-Low-Density Lipoprotein (VLDL)

by Jih-Kai Huang and Hsiang-Chun Lee

Int. J. Mol. Sci. 2022, 23(8), 4300; https://doi.org/10.3390/ijms23084300 - 13 Apr 2022

Cited by 48 | Viewed by 14766

Abstract

Embraced with apolipoproteins (Apo) B and Apo E, triglyceride-enriched very-low-density lipoprotein (VLDL) is secreted by the liver into circulation, mainly during post-meal hours. Here, we present a brief review of the physiological role of VLDL and a systemic review of the emerging evidence supporting its pathological roles. VLDL promotes atherosclerosis in metabolic syndrome (MetS). VLDL isolated from subjects with MetS exhibits cytotoxicity to atrial myocytes, induces atrial myopathy, and promotes vulnerability to atrial fibrillation. VLDL levels are affected by a number of endocrinological disorders and can be increased by therapeutic supplementation with cortisol, growth hormone, progesterone, and estrogen. VLDL promotes aldosterone secretion, which contributes to hypertension. VLDL induces neuroinflammation, leading to cognitive dysfunction. VLDL levels are also correlated with chronic kidney disease, autoimmune disorders, and some dermatological diseases. The extra-hepatic secretion of VLDL derived from intestinal dysbiosis is suggested to be harmful. Emerging evidence suggests disturbed VLDL metabolism in sleep disorders and in cancer development and progression. In addition to VLDL, the VLDL receptor (VLDLR) may affect both VLDL metabolism and carcinogenesis. Overall, emerging evidence supports the pathological roles of VLDL in multi-organ diseases. To better understand the fundamental mechanisms of how VLDL promotes disease development, elucidation of the quality control of VLDL and of the regulation and signaling of VLDLR should be indispensable. With this, successful VLDL-targeted therapies can be discovered in the future. Full article

(This article belongs to the Special Issue Lipids: From the Structure, Function and Evolution to Applications)

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19 pages, 2240 KiB

Open AccessReview

Advances in Lipid Extraction Methods—A Review

by Ramesh Kumar Saini, Parchuri Prasad, Xiaomin Shang and Young-Soo Keum

Int. J. Mol. Sci. 2021, 22(24), 13643; https://doi.org/10.3390/ijms222413643 - 20 Dec 2021

Cited by 230 | Viewed by 33300

Abstract

Extraction of lipids from biological tissues is a crucial step in lipid analysis. The selection of appropriate solvent is the most critical factor in the efficient extraction of lipids. A mixture of polar (to disrupt the protein-lipid complexes) and nonpolar (to dissolve the neutral lipids) solvents are precisely selected to extract lipids efficiently. In addition, the disintegration of complex and rigid cell-wall of plants, fungi, and microalgal cells by various mechanical, chemical, and enzymatic treatments facilitate the solvent penetration and extraction of lipids. This review discusses the chloroform/methanol-based classical lipid extraction methods and modern modifications of these methods in terms of using healthy and environmentally safe solvents and rapid single-step extraction. At the same time, some adaptations were made to recover the specific lipids. In addition, the high throughput lipid extraction methodologies used for liquid chromatography-mass spectrometry (LC-MS)-based plant and animal lipidomics were discussed. The advantages and disadvantages of various pretreatments and extraction methods were also illustrated. Moreover, the emerging green solvents-based lipid extraction method, including supercritical CO₂ extraction (SCE), is also discussed. Full article

(This article belongs to the Special Issue Lipids: From the Structure, Function and Evolution to Applications)

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