Sterol Lipids Research Articles

Effects of apolipoprotein H downregulation on lipid metabolism, fatty liver disease, and gut microbiota dysbiosis

Apolipoprotein H (APOH) downregulation can cause hepatic steatosis and gut microbiota dysbiosis. However, the mechanism by which APOH-regulated lipid metabolism contributes to metabolic dysfunction–associated steatotic liver disease (MASLD) remains undetermined. Herein, we aim to explore the regulatory effect of APOH, mediated through various pathways, on metabolic homeostasis and MASLD pathogenesis. We analyzed serum marker levels, liver histopathology, and cholesterol metabolism–related gene expression in global ApoH−/− C57BL/6 male mice. We used RNA sequencing and metabolomic techniques to investigate the association between liver metabolism and bacterial composition. Fifty-two differentially expressed genes were identified between ApoH−/− and WT mice. The mRNA levels of de novo lipogenesis genes were highly upregulated in ApoH−/− mice than in WT mice. Fatty acid, glycerophospholipid, sterol lipid, and triglyceride levels were elevated, while hyodeoxycholic acid levels were significantly reduced in the liver tissues of ApoH−/− mice than in those of WT mice. Microbial beta diversity was lower in ApoH−/− mice than in WT mice, and gut microbiota metabolic functions were activated in ApoH−/− mice. Moreover, ApoH transcripts were downregulated in patients with MASLD, and APOH-related differential genes were enriched in lipid metabolism. Open-source transcript-level data from human metabolic dysfunction–associated steatohepatitis livers reinforced a significant association between metabolic dysfunction–associated steatohepatitis and APOH downregulation. In conclusion, our studies demonstrated that APOH downregulation aggravates fatty liver and induces gut microbiota dysbiosis by dysregulating bile acids. Our findings offer a novel perspective on APOH-mediated lipid metabolic dysbiosis and provide a valuable framework for deciphering the role of APOH in fatty liver disease.

Untargeted metabolomics reveals potential health risks associated with chronic exposure to environmentally relevant concentrations of 2-Phenylphenol

Chronic exposure to endocrine-disrupting chemicals through foods of aquatic origin, at levels that are commonly found in the environment, can affect metabolic health and lead to metabolic diseases. One such chemical is 2-phenylphenol (2-PP), a suspected endocrine disruptor that is used extensively in agriculture and industry, and has become a widespread pollutant in aquatic environments. This study evaluated the risk of exposure to 2-PP through foods of aquatic origin from Vembanad Lake, using a Target Hazard Quotient (THQ) and an untargeted metabolomics approach. The study found that 2-PP content was higher in samples from areas with intense industrial, tourism, and agricultural activities. The average concentration of 2-PP in fish, crustaceans, and mollusks from the Vembanad estuary ranged from 0.012 to 0.017 mg/kg. The mean concentration of 2-PP was used to assess the THQ of exposure to the coastal population. The results showed that the THQ value was <1, indicating a low to moderate health risk for both adults and children. Furthermore, an untargeted metabolomics approach using HPLC-Q-Orbitrap MS was used to study the metabolome changes associated with chronic exposure to 2-PP (at the environmentally relevant concentration) over 60 days in the Wistar albino rat model. The findings indicated significant alterations in the phospholipid, fatty acid, sterol lipid, and amino acid profiles, suggesting that chronic exposure to 2-PP at environmentally relevant concentrations could affect purine, phenylalanine, tyrosine, and cholesterol metabolism.

Lipidomics Profiling of Metformin-Induced Changes in Obesity and Type 2 Diabetes Mellitus: Insights and Biomarker Potential.

Metformin is the first-line oral medication for treating type 2 diabetes mellitus (T2DM). In the current study, an untargeted lipidomic analytical approach was used to investigate the alterations in the serum lipidome of a cohort of 89 participants, including healthy lean controls and obese diabetic patients, and to examine the alterations associated with metformin administration. A total of 115 lipid molecules were significantly dysregulated (64 up-regulated and 51 down-regulated) in the obese compared to lean controls. However, the levels of 224 lipid molecules were significantly dysregulated (125 up-regulated and 99 down-regulated) in obese diabetic patients compared to the obese group. Metformin administration in obese diabetic patients was associated with significant dysregulation of 54 lipid molecule levels (20 up-regulated and 34 down-regulated). Levels of six molecules belonging to five lipid subclasses were simultaneously dysregulated by the effects of obesity, T2DM, and metformin. These include two putatively annotated triacylglycerols (TGs), one plasmenyl phosphatidylcholine (PC), one phosphatidylglycerol (PGs), one sterol lipid (ST), and one Mannosyl-phosphoinositol ceramide (MIPC). This study provides new insights into our understanding of the lipidomics alterations associated with obesity, T2DM, and metformin and offers a new platform for potential biomarkers for the progression of diabetes and treatment response in obese patients.

Metabolite profiling of wild underutilized raspberry (Rubus pyrifolius)

Rubus pyrifolius J.E. Smith, one of the Rubus species, has been found in Indonesia and collected in the Cibodas Botanical Garden. Rubus species are known for their diverse triterpenes, each with unique biological functions. This research aimed to analyse the metabolite profiles of R. pyrifolius using n-hexane and methanol solvents. GC-MS analysis was used to identify volatile and semi-volatile compounds in the R. pyrifolius extracts, with compound identification based on NIST 17 through GC/MS mass spectra analysis. The results showed that the total number of identified phytochemical compounds in methanol and n-hexane extracts of R. pyrifolius were 115 and 174, respectively. Methanol extracts from R. pyrifolius flower, young leaf, mature leaf, and young stem exhibited 46, 20, 15, and 34 compounds, respectively. In contrast, n-hexane extracts from R. pyrifolius flower, young leaf, mature leaf, and young stem contained 35, 47, 29, and 63 compounds, respectively. These compounds were classified into seven phytochemical groups: alkanes, alkenes, cyclic ethers, diterpenes, fatty acids, triterpenes, and vitamin E. Furthermore, only carboxylic esters, ergosterols, esters, fatty alcohols, and phenols were found in n-hexane extracts. The methanol extract showed seven significant phytochemical groups, including linolenic acid, phthalate esters, phytol, phytosterol, sterol lipids, terpenoids, and triterpenoids. R. pyrifolius possesses a variety of bioactive phytochemical profiles that are relevant in the field of phytopharmaceuticals. Nevertheless, further research is essential to determine their biological activity.

PPARβ/δ-ANGPTL4 axis mediates the promotion of mono-2-ethylhexyl phthalic acid on MYCN-amplified neuroblastoma development

Di-2-ethylhexyl phthalic acid (DEHP) is one of the most widely used plasticizers in the industry, which can improve the flexibility and durability of plastics. It is prone to migrate from various daily plastic products through wear and leaching into the surrounding environment and decompose into the more toxic metabolite mono-2-ethylhexyl phthalic acid (MEHP) after entering the human body. However, the impacts and mechanisms of MEHP on neuroblastoma are unclear. We exposed MYCN-amplified neuroblastoma SK-N-BE(2)C cells to an environmentally related concentration of MEHP and found that MEHP increased the proliferation and migration ability of tumor cells. The peroxisome proliferator-activated receptor (PPAR) β/δ pathway was identified as a pivotal signaling pathway in neuroblastoma, mediating the effects of MEHP through transcriptional sequencing analysis. Because MEHP can bind to the PPARβ/δ protein and initiate the expression of the downstream gene angiopoietin-like 4 (ANGPTL4), the PPARβ/δ-specific agonist GW501516 and antagonist GSK3787, the recombinant human ANGPTL4 protein, and the knockdown of gene expression confirmed the regulation of the PPARβ/δ-ANGPTL4 axis on the malignant phenotype of neuroblastoma. Based on the critical role of PPARβ/δ and ANGPTL4 in the metabolic process, a non-targeted metabolomics analysis revealed that MEHP altered multiple metabolic pathways, particularly lipid metabolites involving fatty acyls, glycerophospholipids, and sterol lipids, which may also be potential factors promoting tumor progression. We have demonstrated for the first time that MEHP can target binding to PPARβ/δ and affect the progression of neuroblastoma by activating the PPARβ/δ-ANGPTL4 axis. This mechanism confirms the health risks of plasticizers as tumor promoters and provides new data support for targeted prevention and treatment of neuroblastoma.

Untargeted Lipidomics Study of Bipolar Disorder Patients in Serbia.

The Lipidomic profiles of serum samples from patients with bipolar disorder (BD) and healthy controls (C) were explored and compared. The sample cohort included 31 BD patients and 31 control individuals. An untargeted lipidomics study applying liquid chromatography (LC) coupled with high-resolution mass spectrometry (HRMS) was conducted to achieve the lipid profiles. Multivariate statistical analyses (principal component analysis and partial least squares discriminant analysis) were performed, and fifty-six differential lipids were confirmed in BD and controls. Our results pointed to alterations in lipid metabolism, including pathways of glycerophospholipids, sphingolipids, glycerolipids, and sterol lipids, in BD patient sera. This study emphasized the role of lipid pathways in BD, and comprehensive research using the LC-HRMS platform is necessary for future application in the diagnosis and improvement of BD treatments.

Abstract 19021: Metabolomic Characterization of Responses to Angiotensin Peptides in Human Brain Microvascular Endothelial Cells

Introduction and hypothesis: Metabolomics offers a robust platform for dissecting the intricate molecular responses of biological models under distinct stimulation scenarios. The mechanism by which Angiotensin 1-7 modulates Angiotensin II signaling in endothelial cells is unclear and may involve events at the cellular membrane or downstream signaling pathways. We hypothesize that metabolomics can help us identify shared and distinct metabolic responses induced by these two molecules. Methods: hCMEC/D3 cells were cultured and then subjected to stimulation with Ang-II and Ang 1-7 during their logarithmic growth phase. Subsequent metabolomic profiling incorporated both RP-LC-QTOF-MS and GC-QTOF-MS analytical techniques. Our data analysis strategy was multilayered, implementing quality control alongside various multivariate statistical methods, such as principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and hierarchical clustering. Results: Our results underscore a discernible pattern of decreased and increased metabolite expression in response to angiotensin treatments, with noteworthy variations observed in the expression of glycerophospholipids, sterol lipids, and sphingolipids amongst the Ang-II, Ang 1-7, and control groups. Intriguingly, an "ON/OFF" pattern for numerous metabolites emerged across the experimental groups, hinting at shared biological activity provoked by both angiotensin treatments. The compounds Erucamide, Dihydroxy-chol-en-oic Acid, and LPE O-19:0;O significantly contributed to the discrimination between Ang-II and Ang 1-7 treatment groups when compared with controls. Conclusions: These findings offer a novel perspective on the distinct metabolic responses induced by Ang-II and Ang 1-7 treatments in hCMEC/D3 cells, and may shed light on the cellular mechanisms that underlie the impact of these angiotensins, and other vasoactive peptides, on the blood-brain barrier. Overall, our study reaffirms the value of metabolomics as a powerful tool for gaining new insights into the molecular effects of vasoactive peptides on endothelial cells.

Methods for the relative quantitation of human plasma lipidome using liquid chromatography coupled with mass spectrometry using minimal sample manipulation.

Extraction protocols and liquid chromatography coupled with mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS/MS) methods for the measurement of four lipid categories, namely glycerophospholipids, glycerolipids, sphingolipids and sterol lipids in human plasma, are described here. Step-by-step instructions are provided for the liquid-liquid extraction methods, including solution preparation and the non-endogenous lipid internal standards used. All instrumental conditions, chromatography columns and solutions required for the LC-MS and LC-MS/MS methods are also provided in detail.

Unraveling the Metabolic Changes in Acute Pancreatitis: A Metabolomics-Based Approach for Etiological Differentiation and Acute Biomarker Discovery.

Acute pancreatitis (AP) remains a challenging medical condition, where a deeper metabolic insight could pave the way for innovative treatments. This research harnessed serum metabolomics to discern potential diagnostic markers for AP and distinguish between its biliary (BAP) and alcohol-induced (AAP) forms. Leveraging high-performance liquid chromatography coupled with mass spectrometry, the metabolic signatures of 34 AP patients were contrasted against 26 healthy participants, and then between different etiologies of AP. The results identified metabolites primarily from glycerophospholipids, glycerolipids, fatty acyls, sterol lipids, and pteridines and derivative classes, with the Human Metabolome Database aiding in classification. Notably, these metabolites differentiated AP from healthy states with high AUROC values above 0.8. Another set of metabolites revealed differences between BAP and AAP, but these results were not as marked as the former. This lipidomic analysis provides an introduction to the metabolic landscape of acute pancreatitis, revealing changes in multiple lipid classes and metabolites and identifying these metabolites. Future research could add and discover new diagnostic biomarkers and therapeutic strategies enhancing the management of acute pancreatitis.

Bisphenol AF Induces Alterations in the Plasma Lipidome of Rats: An Untargeted Lipidomics Approach.

Bisphenol AF has gained popularity as a substitute for bisphenol A in industrial applications, leading to its detection in various biological fluids and raising concerns for public health. While the effects of bisphenol A on lipid metabolism are known, the impact of bisphenol AF on different lipid classes remains understudied. This study aimed to address this gap by conducting an untargeted lipidomics analysis in rats to assess the influence of bisphenol AF on lipid homeostasis. The results of the study revealed significant alterations in lipid profiles in plasma with various lipid classes being affected by bisphenol AF exposure. High-dose exposure to bisphenol AF resulted in specific changes within lipid clusters, including a decrease in the fatty acyl lipid cluster, except for 3,6,9,12,15-octadecapentaenoic acid. Additionally, the compound 9-0-acetyl GTb1(d18:1/18:0) within the gangliosides subclass of the sphingolipids and the sterol lipid clusters was also affected. These findings contribute to a better understanding of how bisphenol AF disrupts lipid metabolism and its associated health effects. This study provides valuable insights into the potential risks posed by bisphenol AF. Further research in this area is warranted to explore the mechanisms underlying the bisphenol AF-induced dysregulation of lipid metabolism and its implications for human health.

An untargeted serum and urine lipidomics research based on UPLC-MS revealed the lipid alterations on adjuvant-induced arthritis rats.

Rheumatoid arthritis (RA) is a systemic autoimmune disease dominated by chronic inflammatory lesions of peripheral synovial joints. Growing evidence suggests that abnormal lipid metabolism levels contribute to the progression of RA. Although several metabolomics studies have shown abnormality in the RA lipidome, the relationship between the overall lipid metabolites and RA has not been systematically evaluated. In this study, an untargeted lipidomics method based on ultra performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the serum and urine lipidomes of adjuvant-induced arthritis rats to study the characteristics of lipid metabolism changes in the rats and search lipid markers for diagnosing RA. By combining with orthogonal partial least squares discriminant analysis, a total of 52 potential lipid markers were identified, mainly involved in sphingolipid metabolism, glycerophospholipid metabolism, sterol lipid metabolism, glycerolipid metabolism and fatty acid metabolism, which provided crucial insight into lipid metabolism disturbances in RA. Further receiver operating characteristic analysis revealed that the areas under the curve of PC(22:4/16:0), PI(18:1/16:0) and LacCer(d18:1/12:0) from serum and 25-hydroxycholesterol from urine were 0.94, 1.00, 1.00 and 1.00, respectively, indicating the high predictive ability of this method for RA. In this study, our results indicated that a combination of serum and urine analysis can provide a more comprehensive and reliable assessment of RA, and a UPLC-MS-based lipidomics strategy is a powerful tool to search for potential lipid markers associated with RA and explore the pathogenesis of RA.

Comparative analysis of sucrose-embedding for whole-body zebrafish MSI by IR-MALDESI.

Infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging (IR-MALDESI) conventionally utilizes fresh-frozen biological tissues with an ice matrix to improve the detection of analytes. Sucrose-embedding with paraformaldehyde fixation has demonstrated feasibility as an alternative matrix for analysis by IR-MALDESI by preserving tissue features and enhancing ionization of lipids. However, investigating multi-organ systems provides broader context for a biological study and can elucidate more information about a disease state as opposed to a single organ. Danio rerio, or zebrafish, are model organisms for various disease states and can be imaged as a multi-organ sample to analyze morphological and metabolomic preservation as a result of sample preparation. Herein, whole-body zebrafish were imaged to compare sucrose-embedding with paraformaldehyde fixation against conventional fresh-frozen sample preparation. Serial sections were analyzed with and without an ice matrix to evaluate if sucrose functions as an alternative energy-absorbing matrix for IR-MALDESI applications across whole-body tissues. The resulting four conditions were compared in terms of total putative lipid annotations and category diversity, coverage across the entire m/z range, and ion abundance. Ultimately, sucrose-embedded zebrafish had an increase in putative lipid annotations for the combination of putative annotations with and without the application of an ice matrix relative to fresh-frozen tissues which require the application of an ice matrix. Upon the use of an ice matrix, a greater number of high mass putative lipid annotations (e.g., glycerophospholipids, glycerolipids, and sphingolipids) were identified. Conversely, without an ice matrix, sucrose-embedded sections elucidated more putative annotations in lower molecular weight lipids, including fatty acyls and sterol lipids. Similar to the mouse brain model, sucrose-embedding increased putative lipid annotation and abundance for whole-body zebrafish.

Aziridination-Assisted Mass Spectrometry of Nonpolar Sterol Lipids with Isomeric Resolution.

Characterization of nonpolar lipids is crucial due to their essential biological functions and ability to exist in various isomeric forms. In this study, we introduce the N-H aziridination method to target carbon-carbon double bonds (C═C bonds) in nonpolar sterol lipids. The resulting fragments are readily dissociated upon collision-induced dissociation, generating specific fragment ions for C═C bond position determination and fingerprint fragments for backbone characterization. This method significantly enhances lipid ionization efficiency, thereby improving the sensitivity and accuracy of nonpolar lipid analysis. We demonstrated that aziridination of sterols leads to distinctive fragmentation pathways for chain and ring C═C bonds, enabling the identification of sterol isomers such as desmosterol and 7-dehydrocholesterol. Furthermore, aziridination can assist in identifying the sterol backbone by providing fingerprint tandem mass spectra. We also demonstrated the quantitative capacity of this approach with a limit of detection of 10 nM in the solvent mixture of methanol and water. To test the feasibility of this method in complex biological samples, we used mouse prostate cancerous tissues and found significant differences in nonpolar lipid profiles between healthy and cancerous samples. The high efficiency and specificity of aziridination-assisted mass spectrometric analysis, as well as its quantitative analysis ability, make it highly suitable for broad applications in nonpolar lipid research.

Enhanced Expression of p53 and Suppression of PI3K/Akt/mTOR by Three Red Sea Algal Extracts: Insights on Their Composition by LC-MS-Based Metabolic Profiling and Molecular Networking.

Brown algae comprise up to 2000 species with wide dissemination in temperate zones. A comprehensive untargeted metabolic profiling guided by molecular networking of three uninvestigated Red-Sea-derived brown algae, namely Sirophysalis trinodis, Polycladia myrica, and Turbinaria triquetra, led to the identification of over 115 metabolites categorized as glycerolipids, fatty acids, sterol lipids, sphingolipids, and phospholipids. The three algae exhibited low-to-moderate antioxidant capacity using DPPH and ABTS assays. Preliminary in vitro antiproliferative studies showed that the algal extracts displayed high cytotoxic activity against a panel of cancer cell lines. The most potent activity was recorded against MCF-7 with IC50 values of 51.37 ± 1.19, 63.44 ± 1.13, and 59.70 ± 1.22 µg/mL for S. trinodis, P. myrica, and T. triquetra, respectively. The cytotoxicity of the algae was selective to MCF-7 without showing notable effects on the proliferation of normal human WISH cells. Morphological studies revealed that the algae caused cell shrinkage, increased cellular debris, triggered detachment, cell rounding, and cytoplasmic condensation in MCF-7 cancer cells. Mechanistic investigations using flow cytometry, qPCR, and Western blot showed that the algae induced apoptosis, initiated cell cycle arrest in the sub-G0/G1 phase, and inhibited the proliferation of cancer cells via increasing mRNA and protein expression of p53, while reducing the expression of PI3K, Akt, and mTOR.

Random forest and live single-cell metabolomics reveal metabolic profiles of human macrophages upon polarization.

Human macrophages are innate immune cells with diverse, functionally distinct phenotypes, namely, pro-inflammatory M1 and anti-inflammatory M2 macrophages. Both are involved in multiple physiological and pathological processes, including would healing, infection, and cancer. However, the metabolic differences between these phenotypes are largely unexplored at single-cell resolution. To address this knowledge gap, an untargeted live single-cell mass spectrometry-based metabolomic profiling coupled with a machine-learning data analysis approach was developed to investigate the metabolic profile of each phenotype at the single-cell level. Results show that M1 and M2 macrophages have distinct metabolic profiles, with differential levels of fatty acyls, glycerophospholipids, and sterol lipids, which are important components of plasma membrane and involved in multiple biological processes. Furthermore, we could discern several putatively annotated molecules that contribute to inflammatory response of macrophages. The combination of random forest and live single-cell metabolomics provided an in-depth profile of the metabolome of primary human M1 and M2 macrophages at the single-cell level for the first time, which will pave the way for future studies targeting the differentiation of other immune cells.

Closed-loop fluid–fluid immiscibility in binary lipid–sterol membranes

We present two binary lipid-sterol membrane systems that exhibit fluid-fluid coexistence. Partial phase diagrams of binary mixtures of dimyristoylphosphatidylcholine with 25-hydroxyxholesterol and 27-hydroxycholesterol, determined from small-angle X-ray scattering and fluorescence microscopy studies, show closed-loop fluid-fluid immiscibility gaps, with the appearance of a single fluid phase both at higher and lower temperatures. Computer simulations suggest that this unusual phase behavior results from the ability of these oxysterol molecules to take different orientations in the membrane depending on the temperature.

Analysis of Lipid Molecule Profiling and Conversion Pathway in Mandarin Fish (Siniperca chuatsi) during Fermentation via Untargeted Lipidomics

Lipids are the key aroma contributors and nutrients in fermented fish products. A total of 376 lipid molecules were identified in mandarin fish during fermentation by untargeted lipidomics, including glycerolipids, glycerophospholipids, lysoglycerophospholipid, sphingolipids, fatty acids (FAs), and sterol lipids. Both lipid composition and content changed dynamically during fermentation. Triglyceride (TAG, 30.05%) and phosphatidylcholine (PC, 14.87%) were the two major lipids, with especially 39.36% saturated FAs in PCs and 35.34% polyunsaturated FAs in TAGs. The content of TAGs and PCs reached a peak point at 0 and 6 days, respectively. Fermented mandarin fish expressed a high nutritional value, and the ratio of total linoleic acid/total linolenic acid was about 5:1. Glycerophospholipid metabolism was a potential metabolic pathway, and the oxidation of derived FAs contributed to flavor. These data progress in understanding lipid dynamic variation during fermentation and provide thoughts on controlling the flavor quality and safety of fermented fish products.

Ebola virus–like particles reprogram cellular metabolism

Ebola virus can trigger a release of pro-inflammatory cytokines with subsequent vascular leakage and impairment of clotting finally leading to multiorgan failure and shock after entering and infecting patients. Ebola virus is known to directly target endothelial cells and macrophages, even without infecting them, through direct interactions with viral proteins. These interactions affect cellular mechanics and immune processes, which are tightly linked to other key cellular functions such as metabolism. However, research regarding metabolic activity of these cells upon viral exposure remains limited, hampering our understanding of its pathophysiology and progression. Therefore, in the present study, an untargeted cellular metabolomic approach was performed to investigate the metabolic alterations of primary human endothelial cells and M1 and M2 macrophages upon exposure to Ebola virus–like particles (VLP). The results show that Ebola VLP led to metabolic changes among endothelial, M1, and M2 cells. Differential metabolite abundance and perturbed signaling pathway analysis further identified specific metabolic features, mainly in fatty acid-, steroid-, and amino acid–related metabolism pathways for all the three cell types, in a host cell specific manner. Taken together, this work characterized for the first time the metabolic alternations of endothelial cells and two primary human macrophage subtypes after Ebola VLP exposure, and identified the potential metabolites and pathways differentially affected, highlighting the important role of those host cells in disease development and progression.Key messages• Ebola VLP can lead to metabolic alternations in endothelial cells and M1 and M2 macrophages.• Differential abundance of metabolites, mainly including fatty acids and sterol lipids, was observed after Ebola VLP exposure.• Multiple fatty acid-, steroid-, and amino acid–related metabolism pathways were observed perturbed.

Integrating the potential of ion mobility spectrometry-mass spectrometry in the separation and structural characterisation of lipid isomers.

It is increasingly evident that a more detailed molecular structure analysis of isomeric lipids is critical to better understand their roles in biological processes. The occurrence of isomeric interference complicates conventional tandem mass spectrometry (MS/MS)-based determination, necessitating the development of more specialised methodologies to separate lipid isomers. The present review examines and discusses recent lipidomic studies based on ion mobility spectrometry combined with mass spectrometry (IMS-MS). Selected examples of the separation and elucidation of structural and stereoisomers of lipids are described based on their ion mobility behaviour. These include fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids. Recent approaches for specific applications to improve isomeric lipid structural information using direct infusion, coupling imaging, or liquid chromatographic separation workflows prior to IMS-MS are also discussed, including: 1) strategies to improve ion mobility shifts; 2) advanced tandem MS methods based on activation of lipid ions with electrons or photons, or gas-phase ion-molecule reactions; and 3) the use of chemical derivatisation techniques for lipid characterisation.

Lipidomic Analysis of Hand Skin Surface Lipids Reveals Smoking-Related Skin Changes

Smoking contributes to the formation of skin wrinkles and reduces skin function, but the mechanism is not yet fully proven. This study aims to compare and analyze the effects of smoking on skin lipids and to further investigate the harmful effects of smoking on the skin. A total of 40 subjects (20 male smokers and 20 healthy control males) were recruited for this study. Measurement of hand skin-surface lipids (SSLs) in smoking and healthy control groups was undertaken using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Multivariate data analysis was used to investigate the differences in SSLs between the two groups. There were 1230 lipids detected in the two groups and significant differences in SSLs' composition were observed between them. Under selected conditions, 26 types of lipid with significant differences were observed between the two groups (p < 0.05). Sphingolipids (SP) and glycerolipids (GL) were significantly increased, and sterol lipids (ST) were significantly reduced. Smoking causes changes in skin lipids that disrupt skin homeostasis, making the skin more fragile and more susceptible to skin aging and diseases.