Progress in lipid research最新文献

The role of cholesterol in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronavirus-host cell interactions is currently being discussed in the context of two main scenarios: i) the presence of the neutral lipid in cholesterol-rich lipid domains involved in different steps of the viral infection and ii) the alteration of metabolic pathways by the virus over the course of infection. Cholesterol-enriched lipid domains have been reported to occur in the lipid envelope membrane of the virus, in the host-cell plasma membrane, as well as in endosomal and other intracellular membrane cellular compartments. These membrane subdomains, whose chemical and physical properties distinguish them from the bulk lipid bilayer, have been purported to participate in diverse phenomena, from virus-host cell fusion to intracellular trafficking and exit of the virions from the infected cell. SARS-CoV-2 recruits many key proteins that participate under physiological conditions in cholesterol and lipid metabolism in general. This review analyses the status of cholesterol and lipidome proteins in SARS-CoV-2 infection and the new horizons they open for therapeutic intervention.

Complex lipids, phospholipids (PLs) and triacylglycerides (TAGs), are prone to modifications induced by reactive nitrated species and reactive oxygen species, generating a range of nitrated, nitrosated or nitroxidized derivatives, as nitro PLs and nitro TAGs. These modified lipids (epilipids) have been reported in vitro and in vivo using lipidomics approaches. However, their detection in living systems remains a challenge hampered by its complexity, high structural diversity, and low abundance. The advances in high-resolution mass spectrometry combined with the higher sensitivity of the instruments like Orbitrap-based mass spectrometers opened new opportunities for the detection of these modified complex lipids. This review summarizes the challenges and findings behind the identification of nitrated, nitrosated and nitroxidized PLs and TAGs fragmentation fingerprints based on collision-induced dissociation (CID) and higher energy CID (HCD) MS/MS approaches. Following what has already been reported for nitrated fatty acids, these complex lipids are found to act as endogenous mediators with potential electrophilic properties and can express bioactivities such as anti-inflammatory and antioxidant actions. This information can be used to design untargeted and targeted lipidomics strategies for these modified complex lipids in biological samples as well as in pathological, food and industrial settings, further unveiling their biological and signalling roles.

The inflammatory response is a complex regulated effector mechanism of the innate immune system that is initiated after tissue injury or infection. The NLRP3 inflammasome is an important initiator of inflammation by regulating the activation of caspase-1, the maturation of pro-inflammatory cytokines and the induction of pyroptotic cell death. Numerous studies demonstrate that the NLRP3 inflammasome could be modulated by lipids, existing a relation between lipids and the activation of different inflammatory processes. In this review we will summarize how the mechanism of NLRP3 inflammasome activation is regulated by different lipids and how these lipids control specific cellular localization of NLRP3 during activation. Although being a cytosolic protein, NLRP3 interacts with lipids accessible in neighbor membranes. Also, the modulation of NLRP3 by endogenous lipids has been found causative of different metabolic diseases and bacterial-pathogenic lipids lead to NLRP3 activation during infection. The understanding of the modulation of the NLRP3 inflammasome by lipids has resulted not only in a better knowledge about the mechanism of NLRP3 activation and its implication in disease, but also opens a new avenue for the development of novel therapeutics and vaccines, as NLRP3 could be modulated by synthetic lipids used as adjuvants.

Fatty acid binding proteins (FABPs) are key proteins in lipid transport, and the isoforms are segregated according to their tissue origins. Several isoforms, such as adipose-FABP and epidermal-FABP, have been shown to participate in multiple pathologic processes due to their ubiquitous expression. Intestinal fatty acid binding protein, also termed FABP2 or I-FABP, is specifically expressed in the small intestine. FABP2 can traffic lipids from the intestinal lumen to enterocytes and bind superfluous fatty acids to maintain a steady pool of fatty acids in the epithelium. As a lipid chaperone, FABP2 can also carry lipophilic drugs to facilitate targeted transport. When the integrity of the intestinal epithelium is disrupted, FABP2 is released into the circulation. Thus, it can potentially serve as a clinical biomarker. In this review, we discuss the pivotal role of FABP2 in intestinal lipid metabolism. We also summarize the molecular interactions that have been reported to date, highlighting the clinical prospects of FABP2 research.

Large ‘omics studies are of particular interest to population and clinical research as they allow elucidation of biological pathways that are often out of reach of other methodologies. Typically, these information rich datasets are produced from multiple coordinated profiling studies that may include lipidomics, metabolomics, proteomics or other strategies to generate high dimensional data. In lipidomics, the generation of such data presents a series of unique technological and logistical challenges; to maximize the power (number of samples) and coverage (number of analytes) of the dataset while minimizing the sources of unwanted variation. Technological advances in analytical platforms, as well as computational approaches, have led to improvement of data quality – especially with regard to instrumental variation. In the small scale, it is possible to control systematic bias from beginning to end. However, as the size and complexity of datasets grow, it is inevitable that unwanted variation arises from multiple sources, some potentially unknown and out of the investigators control. Increases in cohort size and complexity have led to new challenges in sample collection, handling, storage, and preparation. If not considered and dealt with appropriately, this unwanted variation may undermine the quality of the data and reliability of any subsequent analysis. Here we review the various experimental phases where unwanted variation may be introduced and review general strategies and approaches to handle this variation, specifically addressing issues relevant to lipidomics studies.

The plasma membrane is one of the principal structural components of the cell and, therefore, one of the key components of the cellular life. Because the membrane's dynamics links the membrane's structure and function, the complexity and the broad range of the membrane's motions are essential for the enormously diverse functionality of the cell membrane. Even for the main membrane component, the lipid bilayer, considered alone, the range and complexity of the lipid motions are remarkable. Spanning the time scale from sub-picosecond to minutes and hours, the lipid motion in a bilayer is challenging to study even when a broad array of dynamic measurement techniques is employed. Neutron scattering plays a special role among such dynamic measurement techniques, particularly, because it involves the energy transfers commensurate with the typical intra- and inter- molecular dynamics and the momentum transfers commensurate with intra- and inter-molecular distances. Thus, using neutron scattering-based techniques, the spatial and temporal information on the lipid motion can be obtained and analysed simultaneously. Protium vs. deuterium sensitivity and non-destructive character of the neutron probe add to the remarkable prowess of neutron scattering for elucidating the lipid dynamics. Herein we present an overview of the neutron scattering-based studies of lipid dynamics in model membranes, with a discussion of the direct relevance and implications to the real-life cell membranes. The latter are much more complex systems than simple model membranes, consisting of heterogeneous non-stationary domains composed of lipids, proteins, and other small molecules, such as carbohydrates. Yet many fundamental aspects of the membrane behavior and membrane interactions with other molecules can be understood from neutron scattering measurements of the model membranes. For example, such studies can provide a great deal of information on the interactions of antimicrobial compounds with the lipid matrix of a pathogen membrane, or the interactions of drug molecules with the plasma membrane. Finally, we briefly discuss the recently emerging field of neutron scattering membrane studies with a reach far beyond the model membrane systems.

Very long chain fatty acids (VLCFAs) are important components of various lipid classes in most organisms, from bacteria to higher plants and mammals, including humans. VLCFAs, or very long chain polyunsaturated fatty acids (VLCPUFAs), can be defined as fatty acids with 23 or more carbon atoms in the molecule. The main emphasis in this review is on the analysis of these acids, including obtaining standards from natural sources or their synthesis. Furthermore, the occurrence and analysis of these compounds in both lower (bacteria, invertebrates) and higher organisms (flowering plants or mammals) are discussed in detail. Attention is paid to their biosynthesis, especially the elongation of very long chain fatty acids protein (ELOVL4). This review deals with papers describing these very interesting compounds, whose chemical, biochemical and biological properties have not been fully explored.

The last decades revealed that the adipose tissue shows an unexplored therapeutic potential. In particular, targeting the perivascular adipose tissue (PVAT), that surrounds blood vessels, can prevent cardiovascular pathologies and browning of the adipose tissue can become an effective strategy against obesity. Therefore, new analytical tools are necessary to analyze this tissue. This review reports on the recent developments of various Raman-based techniques for the identification and quantification of the adipose tissue compared to conventional analytical methods. In particular, the emphasis is on analysis of PVAT, investigation of pathological changes of the adipose tissue in model systems and possibilities for its characterization in the clinical context. Overall, the review critically discusses the potential and limitations of Raman techniques in adipose tissue-targeted diagnostics and possible future anti-obesity therapies.

Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) are essential fatty acids for the growth, development and survival of virtually all organisms. There is increasing evidence that anthropogenic climate change has a direct and indirect impact on the availability of natural n-3 LC-PUFA. However, this information is fragmented and not well organized. Therefore, this article reviewed published data from laboratory experiments, field experiments and model simulations to reveal the impact of climate change on the global supply of natural n-3 LC-PUFA and how this will limit the availability of n-3 LC-PUFA in the future food web. In general, climate change can significantly reduce the availability of natural n-3 LC-PUFA in grazing food webs in the following ways: 1) decrease the total biomass of phytoplankton and shift the plankton community structure to a smaller size, which also reduce the biomass of animals in higher trophics; 2) reduce the n-3 LC-PUFA content and/or quality (n-3: n-6 ratio) of all marine organisms; 3) reduce the transfer efficiency of n-3 LC-PUFA in grazing food web. In addition, as an anthropogenic climate adaptation measure, this review also proposed some alternative sources of n-3 LC-PUFA and determined the direction of future research. The information in this article is very useful for providing a critical analysis of the impact of climate change on the supply of natural n-3 LC-PUFA. Such information will aid to establish climate adaptation or management measures, and determine the direction of future research.

Intestinal cholesterol absorption varies widely between individuals, which may translate into differences in responsiveness to cholesterol-lowering drugs or diets. Therefore, understanding the importance of genetic variation on cholesterol absorption rates and the complex intestinal cholesterol network is important. Based on a systematic review, genetic variants in seven genes (ABCG5, ABCG8, ABO, APOE, MTTP, NPC1L1, and LDLR) were identified that were associated with intestinal cholesterol absorption. No clear associations were found for variants in APOA4, APOB, CETP, CYP7A1, HMGCR, SCARB1, SLCO1B1, and SREBF1. The seven genes were used to construct an intestinal cholesterol absorption network. Finally, a network with fifteen additional genes (APOA1, APOA4, APOB, APOC2, APOC3, CETP, HSPG2, LCAT, LDLRAP1, LIPC, LRP1, OLR1, P4HB, SAR1B, and SDC1) was generated. The constructed network shows that cholesterol absorption is complex. Further studies are needed to validate and improve this network, which may ultimately lead to a better understanding of the wide inter-individual variability in intestinal cholesterol absorption and the development of personalized interventions.