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BMC Genomics Jun 2024Global per capita meat consumption continues to rise, especially pork. Meat quality is influenced by the content of intramuscular fat (IMF) as a key factor. The...
BACKGROUND
Global per capita meat consumption continues to rise, especially pork. Meat quality is influenced by the content of intramuscular fat (IMF) as a key factor. The longissimus dorsi muscle of Dahe pigs (DHM, IMF: 7.98% ± 1.96%) and Dahe black pigs (DHBM, IMF: 3.30% ± 0.64%) was studied to explore cellular heterogeneity and differentially expressed genes (DEGs) associated with IMF deposition using single-nucleus RNA sequencing (snRNA-seq). The lipid composition was then analyzed using non-targeted lipidomics.
RESULTS
A total of seven cell subpopulations were identified, including myocytes, fibroblast/fibro/adipogenic progenitors (FAPs), satellite cells, endothelial cells, macrophages, pericytes, and adipocytes. Among them, FAPs and adipocytes were more focused because they could be associated with lipid deposition. 1623 DEGs in the FAPs subpopulation of DHBM were up-regulated compared with DHM, while 1535 were down-regulated. These DEGs enriched in the glycolysis/gluconeogenesis pathway. 109 DEGs were up-regulated and 806 were down-regulated in the adipocyte subpopulation of DHBM compared with DHM, which were mainly enriched in the PPAR signaling pathway and fatty acid (FA) biosynthesis. The expression level of PPARG, ABP4, LEP, and ACSL1 genes in DHM was higher than that in DHBM. Lipidomics reveals porcine lipid composition characteristics of muscle tissue. A total of 41 lipid classes and 2699 lipid species were identified in DHM and DHBM groups. The top ten relative peak areas of lipid classes in DHM and DHBM were triglyceride (TG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), diglyceride (DG), cardiolipin (CL), ceramides (Cer), Simple Glc series (Hex1Cer), sphingomyelin (phSM), and phosphatidylinositol (PI). The relative peak areas of 35 lipid species in DHM were lower than DHBM, and 28 lipid species that were higher. There was a significant increase in the TG fatty acyl chains C6:0, C17:0, and C11:4, and a significant decrease in C16:0, C18:1, C18:2, and C22:4 in DHBM (p < 0.05).
CONCLUSIONS
C16:0 FA may downregulate the expression level of PPARG gene, which leads to the downregulation of fat metabolism-related genes such as ACSL, PLIN2, and FABP4 in DHBM compared with DHM. This may be the reason that the lipid deposition ability of Dahe pigs is stronger than that of Dahe black pigs, which need further investigation.
Topics: Animals; Swine; Muscle, Skeletal; Lipid Metabolism; Lipidomics; Sequence Analysis, RNA; Single-Cell Analysis; Lipids; Gene Expression Profiling
PubMed: 38902599
DOI: 10.1186/s12864-024-10488-8 -
The Journal of Nutrition Jun 2024Healthy plant-based diets have been associated with lower risk of type 2 diabetes (T2D). Metabolomics can be leveraged to identify potential pathways through which diet...
BACKGROUND
Healthy plant-based diets have been associated with lower risk of type 2 diabetes (T2D). Metabolomics can be leveraged to identify potential pathways through which diet influences disease risk.
OBJECTIVE
To identify profiles of serum metabolites reflective of plant-based diets of varying quality and examine associations with cardiometabolic risk and T2D.
METHODS
We included data from 687 participants of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort. An overall plant-based diet index (PDI), healthy PDI (hPDI), and unhealthful PDI (uPDI) were estimated from food frequency questionnaires. Serum metabolites were assayed using ultra-performance liquid chromatography mass spectrometry. Elastic net regression was used to identify sets of metabolites predictive of each diet index and metabolite profile scores were calculated as the weighted sum of the selected metabolites. Cross-sectional associations between metabolite profile scores and cardiometabolic measures and prospective associations with incident T2D were evaluated with multivariable adjusted linear and logistic regressions.
RESULTS
Metabolite profiles for PDI, hPDI, and uPDI consisted of n=51, 55, and 45 metabolites, respectively. Metabolites strongly positively correlated with diet indices included phosphatidylcholine (16:0/18:3) for PDI, phosphatidylethanolamine (20:1/20:4) and pantothenate for hPDI, and lysophosphatidylglycerol (18:2/0:0), proline, and lauric acid for uPDI. Higher metabolite profile scores for PDI and hPDI were associated with lower glycemia and lipids measures, whereas a higher uPDI metabolite score was associated with higher triglycerides and lower LDL-C and HDL-C. A higher metabolite score for hPDI was additionally associated with lower adiposity measures, higher liver fat attenuation, higher adiponectin), lower odds of overweight and obesity (OR 0.64 [95% CI: 0.51-0.81] and 0.59 [95% CI: 0.48-0.74], respectively) and lower odds of incident T2D (OR 0.66 [95% CI: 0.45-0.97]).
CONCLUSION
Metabolite profiles of different plant-based diets were identified. Metabolite profiles of overall and healthy plant-based diets were associated with favorable cardiometabolic risk profiles.
PubMed: 38901635
DOI: 10.1016/j.tjnut.2024.06.007 -
Journal of Chromatography. B,... Jun 2024Lipidomics is focusing on the screening of lipid species in complex mixtures using mass spectrometry-based approaches. In this work, we aim to enhance the intestinal...
Lipidomics is focusing on the screening of lipid species in complex mixtures using mass spectrometry-based approaches. In this work, we aim to enhance the intestinal lipidome coverage within the Oligo-Mouse-Microbiota (OMM) colonized mouse model by testing eight mobile phase conditions on five reversed-phase columns. Our selected mobile phase modifiers included two ammonium salts, two concentrations, and the addition of respective acids at 0.1 %. We compared two columns with hybrid surface technology, two with ethylene bridged hybrid technology and one with core-shell particles. Best performance was attained for standards and intestinal lipidome, using either ammonium formate or acetate in ESI(+) or ammonium acetate in ESI(-) for all column technologies. Notably, a concentration of 5 mM ammonium salt showed optimal results for both modes, while the addition of acids had a negligible effect on lipid ionization efficiency. The HST BEH C18 column improved peak width and tailing factor parameters compared to other technologies. We achieved the highest lipid count in colon and ileum content, including ceramides, phosphatidylethanolamines and phosphatidylcholines, when using 5 mM ammonium acetate in ESI(-). Conversely, in ESI(+) 5 mM ammonium formate demonstrated superior coverage for diacylglycerols and triacylglycerols.
PubMed: 38901159
DOI: 10.1016/j.jchromb.2024.124188 -
Cell Reports Jun 2024Protective immunity to dengue virus (DENV) requires antibody response to all four serotypes. Systems vaccinology identifies a multi-OMICs pre-vaccination signature and...
Protective immunity to dengue virus (DENV) requires antibody response to all four serotypes. Systems vaccinology identifies a multi-OMICs pre-vaccination signature and mechanisms predictive of broad antibody responses after immunization with a tetravalent live attenuated DENV vaccine candidate (Butantan-DV/TV003). Anti-inflammatory pathways, including TGF-β signaling expressed by CD68 monocytes, and the metabolites phosphatidylcholine (PC) and phosphatidylethanolamine (PE) positively correlate with broadly neutralizing antibody responses against DENV. In contrast, expression of pro-inflammatory pathways and cytokines (IFN and IL-1) in CD68 monocytes and primary and secondary bile acids negatively correlates with broad DENV-specific antibody responses. Induction of TGF-β and IFNs is done respectively by PC/PE and bile acids in CD68 and CD68 monocytes. The inhibition of viral sensing by PC/PE-induced TGF-β is confirmed in vitro. Our studies show that the balance between metabolites and the pro- or anti-inflammatory state of innate immune cells drives broad and protective B cell response to a live attenuated dengue vaccine.
PubMed: 38900640
DOI: 10.1016/j.celrep.2024.114370 -
Advanced Science (Weinheim,... Jun 2024Non-alcoholic fatty liver disease (NAFLD) is a prominent cause of various chronic metabolic hepatic diseases with limited therapeutics. Rubicon, an essential regulator...
Non-alcoholic fatty liver disease (NAFLD) is a prominent cause of various chronic metabolic hepatic diseases with limited therapeutics. Rubicon, an essential regulator in lysosomal degradation, is reported to exacerbate hepatic steatosis in NAFLD mice and patients, indicating its probability of being a therapeutic target for NAFLD treatment. In this study, the therapeutic potential of Rubicon blockage is investigated. Lipid nanoparticles carrying Rubicon-specific CRISPR-Cas9 components exhibited liver accumulation, cell internalization, and Rubicon knockdown. A single administration of the nanoparticles results in attenuated lipid deposition and hepatic steatosis, with lower circulating lipid levels and decreased adipocyte size in NAFLD mice. Furthermore, the increase of phosphatidylcholine and phosphatidylethanolamine levels can be observed in the NAFLD mice livers after Rubicon silencing, along with regulatory effects on metabolism-related genes such as CD36, Gpcpd1, Chka, and Lpin2. The results indicate that knockdown of Rubicon improves glycerophospholipid metabolism and thereby ameliorates the NAFLD progression, which provides a potential strategy for NAFLD therapy via the restoration of Rubicon.
PubMed: 38894572
DOI: 10.1002/advs.202400493 -
Cancers May 2024This review delves into the enzymatic processes governing the initial stages of glycerophospholipid (phosphatidylcholine, phosphatidylethanolamine, and... (Review)
Review
This review delves into the enzymatic processes governing the initial stages of glycerophospholipid (phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine) and triacylglycerol synthesis. The key enzymes under scrutiny include GPAT and AGPAT. Additionally, as most AGPATs exhibit LPLAT activity, enzymes participating in the Lands cycle with similar functions are also covered. The review begins by discussing the properties of these enzymes, emphasizing their specificity in enzymatic reactions, notably the incorporation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid and docosahexaenoic acid (DHA) into phospholipids. The paper sheds light on the intricate involvement of these enzymes in various diseases, including obesity, insulin resistance, and cancer. To underscore the relevance of these enzymes in cancer processes, a bioinformatics analysis was conducted. The expression levels of the described enzymes were correlated with the overall survival of patients across 33 different types of cancer using the GEPIA portal. This review further explores the potential therapeutic implications of inhibiting these enzymes in the treatment of metabolic diseases and cancer. By elucidating the intricate enzymatic pathways involved in lipid synthesis and their impact on various pathological conditions, this paper contributes to a comprehensive understanding of these processes and their potential as therapeutic targets.
PubMed: 38893234
DOI: 10.3390/cancers16112115 -
Journal of Nanobiotechnology Jun 2024Osteoarthritis (OA) is a common degenerative joint disease which currently lacks of effective agents. It is therefore urgent and necessary to seek an effective approach...
Cartilage progenitor cells derived extracellular vesicles-based cell-free strategy for osteoarthritis treatment by efficient inflammation inhibition and extracellular matrix homeostasis restoration.
Osteoarthritis (OA) is a common degenerative joint disease which currently lacks of effective agents. It is therefore urgent and necessary to seek an effective approach that can inhibit inflammation and promote cartilage matrix homeostasis. Cartilage progenitor cells (CPCs) are identified as a cell population of superficial zone in articular cartilage which possess strong migration ability, proliferative capacity, and chondrogenic potential. Recently, the application of CPCs may represent a novel cell therapy strategy for OA treatment. There is growing evidence that extracellular vesicles (EVs) are primary mediators of the benefits of stem cell-based therapy. In this study, we explored the protective effects of CPCs-derived EVs (CPCs-EVs) on IL-1β-induced chondrocytes. We found CPCs-EVs exhibited chondro-protective effects in vitro. Furthermore, our study demonstrated that CPCs-EVs promoted matrix anabolism and inhibited inflammatory response at least partially via blocking STAT3 activation. In addition, liquid chromatography-tandem mass spectrometry analysis identified 991 proteins encapsulated in CPCs-EVs. By bioinformatics analysis, we showed that STAT3 regulatory proteins were enriched in CPCs-EVs and could be transported to chondrocytes. To promoting the protective function of CPCs-EVs in vivo, CPCs-EVs were modified with cationic peptide ε-polylysine-polyethylene-distearyl phosphatidylethanolamine (PPD) for surface charge reverse. In posttraumatic OA mice, our results showed PPD modified CPCs-EVs (PPD-EVs) effectively inhibited extracellular matrix catabolism and attenuated cartilage degeneration. Moreover, PPD-EVs down-regulated inflammatory factors expressions and reduced OA-related pain in OA mice. In ex-vivo cultured OA cartilage explants, PPD-EVs successfully promoted matrix anabolism and inhibited inflammation. Collectively, CPCs-EVs-based cell-free therapy is a promising strategy for OA treatment.
Topics: Extracellular Vesicles; Animals; Osteoarthritis; Extracellular Matrix; Mice; Chondrocytes; Inflammation; Cartilage, Articular; Stem Cells; Homeostasis; Mice, Inbred C57BL; Male; STAT3 Transcription Factor; Cells, Cultured; Interleukin-1beta
PubMed: 38890638
DOI: 10.1186/s12951-024-02632-z -
Journal of Microbiological Methods Jun 2024The mucin-degrading gut commensal Akkermansia muciniphila (A. muciniphila) negatively correlates with various diseases, including metabolic disorders, neurodegenerative...
The mucin-degrading gut commensal Akkermansia muciniphila (A. muciniphila) negatively correlates with various diseases, including metabolic disorders, neurodegenerative disorders, and cancers, through interacting with host receptors by diverse molecules. Still, their exact metabolic capability within the nutrient-rich environment (such as in the human gut) is not fully characterized. Therefore, in the present study, we investigated the comprehensive metabolome and lipidome of A. muciniphila after supplementation of four major gut microbial nutrients: mucin, inorganic salts, bile salts, and short-chain fatty acids (SCFAs). Our results showed that mucin is the predominant driver of the different lipidomic and metabolomic profiles of A. muciniphila, and it promotes the overall growth of this bacteria. While the addition of inorganic salts, bile salts, and SCFAs was found to inhibit the growth of A. muciniphila. Interestingly, inorganic salts affected the purine metabolism in A. muciniphila cultures, while adding bile salts significantly increased the production of other bile acids and N-acyl amides. Lastly, SCFAs were identified to alter the A. muciniphila energy utilization of triglycerides, fatty acyls, and phosphatidylethanolamines. To our knowledge, this is the first study to examine the comprehensive lipidome and metabolome of A. muciniphila, which highlights the importance of nutritional impacts on the lipidome and metabolome of A. muciniphila and hence providing foundational knowledge to unveil the potential effects of A. muciniphila on host health.
PubMed: 38889842
DOI: 10.1016/j.mimet.2024.106975 -
International Journal of Systematic and... Jun 2024A novel bacterial strain, designated as MAH-18, was isolated from soil sampled in a flower garden. Cells of strain MAH-18 were Gram-stain-positive, aerobic, motile, and...
A novel bacterial strain, designated as MAH-18, was isolated from soil sampled in a flower garden. Cells of strain MAH-18 were Gram-stain-positive, aerobic, motile, and rod-shaped. The colonies were beige in colour, smooth, and spherical when grown on Reasoner's 2A agar medium. Strain MAH-18 grew at 20-40 °C, pH 6.0-8.0, and 0-1.0 % NaCl. Cells were able to hydrolyse aesculin, gelatin, and Tween 20. According to the 16S rRNA gene sequence comparisons, the isolate was determined to be a member of the genus and most closely related to OS4 (97.9 %), DS-30 (97.9 %), GW-9 (97.6 %), mbc-2 (97.5 %), HWE 2-02 (97.4 %), and GBK3QG-3 (96.3 %). Strain MAH-18 has a draft genome size of 4 788 325 bp (eight contigs), 4572 protein-coding genes, 46 tRNA, and three rRNA genes. The average nucleotide identity and digital DNA-DNA hybridization values between strain MAH-18 and the closest type strains were 81.5-83.4 % and 24.4-25.8 %, respectively. genome mining revealed several biosynthetic gene clusters in the genome of the novel strain MAH-18. The G+C content of the genomic DNA of strain was 72.2 mol% and the predominant isoprenoid quinone was MK-8 (H). The main polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, and unknown phospholipids. The major cellular fatty acids were determined to be C iso and C 6. The DNA-DNA hybridization results and phenotypic, genotypic, and chemotaxonomic data demonstrated that strain MAH-18 represents a novel species, for which the name sp. nov. is proposed, with MAH-18 as the type strain (=KACC 19744=CGMCC 1.13656).
Topics: Soil Microbiology; Fatty Acids; Base Composition; RNA, Ribosomal, 16S; Phylogeny; DNA, Bacterial; Nucleic Acid Hybridization; Sequence Analysis, DNA; Bacterial Typing Techniques; Actinomycetales; Genome, Bacterial; Gardens; Phospholipids
PubMed: 38888593
DOI: 10.1099/ijsem.0.006407 -
Frontiers in Physiology 2024Intrahepatic cholestasis of pregnancy (ICP) stands as the predominant liver disorder affecting pregnant women, with a prevalence ranging from 0.2% to 15.6%. While ICP...
Intrahepatic cholestasis of pregnancy (ICP) stands as the predominant liver disorder affecting pregnant women, with a prevalence ranging from 0.2% to 15.6%. While ICP is known to heighten the chances of perinatal mortality and morbidity, its pathogenesis remains elusive, and therapeutic options are limited. The objective of this study was to explore the characteristic lipid signature in placentas collected from normal pregnancies and those with mild and severe intrahepatic cholestasis of pregnancy. This research aims to clarify the pathogenesis and identify lipid biomarker for ICP through LC-MS/MS based lipidomic analysis. Placenta samples were collected from 30 normal pregnancy women and 30 mild and severe ICP women respectively. Women with normal pregnancy and ICP were recruit from April 2021 to July 2022 in Chengdu, China. And LC-MS/MS based lipidomic analysis was used to explore the characteristic placental lipids in mild and severe ICP. Fourty-four lipids were differentially expressed both in mild and severe ICP placenta. The pathway analysis revealed these lipids are mainly enriched in glycerophospholipid metabolism and autophagy pathway. Weighted correlation network analysis (WGCNA) identified the correlation network module of lipids highly related to ICP. Using multiple logistic regression analysis, we identified three and four combined metabolites that had an area under receiver operating characteristic curves (AUC) ≥ 0.90. Our results systematically revealed the lipid signature in mild and severe ICP placenta. The results may provide new insight into the treatment and early prediction of ICP.
PubMed: 38887316
DOI: 10.3389/fphys.2024.1276722