Rationale
Fatty acid esters of hydroxy fatty acids (FAHFAs) are recently discovered endogenous lipids with outstanding health benefits. FAHFAs are known to exhibit antioxidant, antidiabetic and ...anti‐inflammatory properties. The number of known long‐chain FAHFAs in mammalian tissues and dietary resources increased recently because of the latest developments in high‐resolution tandem mass spectrometry techniques. However, there are no reports on the identification of short‐chain fatty acid esterified hydroxy fatty acids (SFAHFAs).
Methods
Intestinal contents, tissues, and plasma of rats fed with high‐fat diet (HFD) and normal diet (ND) were analyzed for fatty acids, hydroxy fatty acids, and FAHFAs using ultra‐high‐performance liquid chromatography (UHPLC) and linear trap quadrupole‐Orbitrap mass spectrometry (LTQ Orbitrap MS) with negative heated electrospray ionization.
Results
Untargeted analysis of total lipid extracts from murine samples (male 13‐week‐old WKAH/HKmSlc rats) led to the identification of several new SFAHFAs of acetic acid or propanoic acid esterified long‐chain (>C20)‐hydroxy fatty acids. Furthermore, MS3 analysis revealed the position of the hydroxyl group in the long‐chain fatty acid as C‐2. The relative amounts of SFAHFAs were quantified in intestinal contents and their tissues (Cecum, small intestine, and large intestine), liver, and plasma of rats fed with HFD and ND. The large intestine showed the highest abundance of SFAHFAs with a concentration range from 0.84 to 57 pmol/mg followed by the cecum with a range of 0.66 to 28.6 pmol/mg. The SFAHFAs were significantly altered between the HFD and ND groups, with a strong decreasing tendency under HFD conditions.
Conclusions
Identification of these novel SFAHFAs can contribute to a better understanding of the chemical and biological properties of individual SFAHFAs and their possible sources in the gut, which in turn helps us tackle the role of these lipids in various metabolic diseases.
Myocardial infarction (MI) is a leading cause of heart failure (HF). After MI, lipids undergo several phasic changes implicated in cardiac repair if inflammation resolves on time. However, if ...inflammation continues, that leads to end stage HF progression and development. Numerous studies have analyzed the traditional risk factors; however, temporal lipidomics data for human and animal models are limited. Thus, we aimed to obtain sequential lipid profiling from acute to chronic HF.
Here, we report the comprehensive lipidome of the hearts from diseased and healthy subjects. To induce heart failure in mice, we used a non-reperfused model of coronary ligation, and MI was confirmed by echocardiography and histology, then temporal kinetics of lipids in different tissues (heart, spleen, kidney), and plasma was quantitated from heart failure mice and compared with naïve controls. For lipid analysis in mouse and human samples, untargeted liquid chromatography-linear trap quadrupole orbitrap mass spectrometry (LC-LTQ-Orbitrap MS) was performed.
In humans, multivariate analysis revealed distinct cardiac lipid profiles between healthy and ischemic subjects, with 16 lipid species significantly downregulated by 5-fold, mainly phosphatidylethanolamines (PE), in the ischemic heart. In contrast, PE levels were markedly increased in mouse tissues and plasma in chronic MI, indicating possible cardiac remodeling. Further, fold change analysis revealed site-specific lipid biomarkers for acute and chronic HF. A significant decrease in sulfatides (SHexCer (34:1; 2O)) and sphingomyelins (SM (d18:1/16:0)) was observed in mouse tissues and plasma in chronic HF.
Overall, a significant decreased lipidome in human ischemic LV and differential lipid metabolites in the transition of acute to chronic HF with inter-organ communication could provide novel insights into targeting integrative pathways for the early diagnosis or development of novel therapeutics to delay/prevent HF.
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•A first integrative study using human and murine hearts on association of lipids in heart failure was investigated.•Lipid fingerprinting led to the identification of 273 species in clinical and mouse samples.•A decrease in cardiac phosphatidylethanolamines is associated with human ischemic heart disease.•Inter-organ (heart, spleen, and kidney) and systemic lipid signatures were profiled in acute and chronic HF post-MI mice.
GPR34 is a recently identified G-protein coupled receptor, which has an immunomodulatory role and recognizes lysophosphatidylserine (LysoPS) as a putative ligand. Here, we report cryo-electron ...microscopy structures of human GPR34-G
complex bound with one of two ligands bound: either the LysoPS analogue S3E-LysoPS, or M1, a derivative of S3E-LysoPS in which oleic acid is substituted with a metabolically stable aromatic fatty acid surrogate. The ligand-binding pocket is laterally open toward the membrane, allowing lateral entry of lipidic agonists into the cavity. The amine and carboxylate groups of the serine moiety are recognized by the charged residue cluster. The acyl chain of S3E-LysoPS is bent and fits into the L-shaped hydrophobic pocket in TM4-5 gap, and the aromatic fatty acid surrogate of M1 fits more appropriately. Molecular dynamics simulations further account for the LysoPS-regioselectivity of GPR34. Thus, using a series of structural and physiological experiments, we provide evidence that chemically unstable 2-acyl LysoPS is the physiological ligand for GPR34. Overall, we anticipate the present structures will pave the way for development of novel anticancer drugs that specifically target GPR34.
The brain is a complex organ demonstrated by the occurrence of specific types of functional lipids. Despite some studies focusing on providing the animal brain lipid signature, there are limited ...studies focusing on the comprehensive and regiospecific characterization of multiple animal brain lipidome. Herein we characterized about 294 lipid molecular species from six different lipid classes in different portions of the brain after fixation from mammals of different habitats, fully-aquatic (n = 6), semi-aquatic (n = 6), and terrestrial (n = 4), using liquid chromatography-mass spectrometry. The untargeted brain lipid profiling revealed a significant difference in total lipid levels between fully-aquatic, semi-aquatic, and terrestrial mammals. The polyunsaturated fatty acids and cholesterol esters are abundant in brain tissue of semi-aquatic followed by fully-aquatic mammals whereas phosphatidylethanolamines are profoundly high in terrestrial species. The regiospecific analysis revealed a predominance of sphingolipids in all the groups but no significant differences were observed between the different portions of the brain such as the cerebellum, cortex, pons, spinal cord, and thalamus. Interestingly the multivariate analysis showed almost the same lipid compositions in the spinal cord and thalamus of terrestrial mammals. Overall, this is the first report to compare the comprehensive brain-lipidome among different mammalian groups inhabiting three distinct habitats. These results indicate that the brain lipid composition is specific to the animal habitat.
Herbal teas and beverages have gained global attention because they are rich in natural bioactive compounds, which are known to have diverse biological effects, including antioxidant and ...anticarcinogenic properties. However, the lipidomic profiles of herbal teas remain unclear. In this study, we applied an untargeted lipidomics approach using high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry to comprehensively profile, compare, and identify unknown lipids in four herbal teas: dokudami, kumazasa, sugina, and yomogi. A total of 341 molecular species from five major classes of lipids were identified. Multivariate principal component analysis revealed distinct lipid compositions for each of the herbs. The fatty acid α-linolenic acid (FA 18:3) was found to be abundant in kumazasa, whereas arachidonic acid (FA 20:4) was the most abundant in sugina. Interestingly, novel lipids were discovered for the first time in plants; specifically, short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs) with 4-hydroxy phenyl nonanoic acid as the structural core. This study provides insight into the lipidomic diversity and potential bioactive lipid components of herbal teas, offering a foundation for further research into their health-promoting properties and biological significance.
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•Lipid fingerprinting of four types of herbs led to the detection of 341 lipid species.•Multivariate analysis revealed distinct lipid compositions for each herbal tea.•Novel short-chain fatty acid esters of hydroxy fatty acids are uncovered in herbs.•The abundance of PUFAs in herbal tea made it an excellent choice as a health promotional drink.
Short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs) are a new class of endogenous lipids belonging to the fatty acid esters of the hydroxy fatty acid family. We previously uncovered their ...chemical structure and discussed their potential biological significance. We anticipate an increased need for SFAHFA measurements as markers of metabolic and inflammatory health. In this study, we synthesized sixty isomeric SFAHFAs by combining 12 hydroxy fatty acids (C16–C24) and five short-chain fatty acids (C2–C6) including a labelled internal standard. SFAHFA enrichment was achieved by solid-phase extraction and established a sensitive method for their quantitation by targeted LC-MS/MS. The method was applied to profile SFAHFAs in intestinal contents and fecal samples collected from rats fed a high-fat diet (HFD). The results demonstrated a significant decrease in SFAHFAs in the intestinal contents of the HFD group compared with the control group. The fecal time course (0–8 weeks) profile of SFAHFAs showed significant downregulation of acetic and propanoic acid esters in just 2 weeks after HFD administration. This study offers the first synthesis and quantitation method for SFAHFAs, demonstrating their potential use in elucidating SFAHFA sources, their role in various diseases, and potential biochemical signalling pathways.
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•A first synthesis of sixty isomeric Short Chain Fatty acid Esters of Hydroxy Fatty acids (SFAHFAs) was achieved.•Quantitative LC/MS method for the determination of SFAHFAs was developed.•Regio-specific distributions of SFAHFAs in the rat intestine was studied.•High-fat diet decreased the acetic acid and propanoic acid derived SFAHFAs in rat intestinal contents and feces.
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