Ask about this productRelated genes to: SLC27A3 Blocking Peptide
- Gene:
- SLC27A3 NIH gene
- Name:
- solute carrier family 27 member 3
- Previous symbol:
- -
- Synonyms:
- FATP3, MGC4365, ACSVL3
- Chromosome:
- 1q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-08-20
- Date modifiied:
- 2016-10-05
Related products to: SLC27A3 Blocking Peptide
Related articles to: SLC27A3 Blocking Peptide
- Peri-lesional microglia are particularly sensitive to traumatic brain injury (TBI)-induced disruption of brain lipid homeostasis. This disruption is characterized by elevated levels of acylcarnitines and phospholipids in acute lipidomic profiling, reflecting global lipid alterations. Under physiological conditions, microglial lipid processing involves fatty acid uptake, storage, and mitochondrial oxidation. However, following TBI, excessive fatty acid uptake promotes lipid droplet accumulation, mitochondrial stress, and pro-inflammatory activation. In this study, we investigated whether modulating this process confers therapeutic benefits. Trilobatin (Tri), a natural flavonoid glycoside with potent immunometabolic modulatory activity, markedly reduced neuroinflammation and neuropathological damage while improving motor and cognitive performance in a mouse model of TBI. Integrated transcriptomic and metabolomic analyses revealed that Tri reduced excessive mitochondrial lipid accumulation, alleviated mitochondrial damage, and inhibited mitochondrial DNA release, thereby blocking the TLR9/MyD88/P-P65 pro-inflammatory pathway. Further screening and validation identified that Tri downregulates the lipid transporter SLC27A3, limits excessive lipid uptake, and consequently alleviates microglial pro-inflammatory responses driven by lipid overload. Collectively, these findings establish a link between microglial lipid metabolism and inflammatory activation and support trilobatin as a promising therapeutic agent targeting metabolic-inflammatory crosstalk in acute neural injury. - Source: PubMed
Publication date: 2026/05/13
Zhang Hui-WenWang Xue-JieChu Mao-MaoXing Guang-YuanQiu KaiZhang Yu-GeZhang Wen-FengZhang Yu-TongLiu XueLi LeiLu Xiao-WeiHuang Xin-XinZhang Lei-YangZhang Zhi-Yuan - Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease affecting the axial skeleton, characterized by progressive structural damage and functional impairment. Although biologic therapies targeting tumor necrosis factor and interleukin-17 have improved clinical outcomes, a substantial proportion of patients fail to achieve sustained disease control. Emerging evidence suggests that metabolic alterations may contribute to AS pathogenesis; however, systematic characterization of metabolism-related biomarkers and their regulatory networks remains limited, and the interplay between metabolic dysfunction and immune dysregulation in AS is poorly understood. Two whole-blood GEO datasets (GSE25101, GSE73754; = 104) were integrated as the primary analytical cohort. A third dataset (GSE11886, = 18; monocyte-derived macrophages) was included for exploratory cross-tissue analysis. Differential expression analysis identified 847 DEGs, which were refined to 16 metabolism-related genes through weighted gene co-expression network analysis (WGCNA) and GeneCards database filtering. Eleven machine learning algorithms with 5-fold cross-validation were applied to construct diagnostic models and identify hub genes. Validation analyses included immune cell infiltration estimation using CIBERSORT, metabolic pathway activity assessment via ssGSEA, single-cell transcriptomics from GSE268839, functional enrichment through GSEA/GSVA, and chromosomal localization analysis. A competing endogenous RNA (ceRNA) regulatory network was constructed to map post-transcriptional regulation. Natural compounds from 66 AS-treating traditional Chinese medicines were screened against hub genes using deep learning-based binding prediction. Multiple machine learning algorithms achieved comparable cross-validated performance (CV AUC range 0.741-0.836; top five models: 0.805-0.836) using the six hub genes (, , , , , ) identified through SHAP-based feature importance analysis of the PLS model. Leave-one-dataset-out validation between the two whole-blood cohorts showed that all algorithms exceeded an AUC of 0.77 in Round 1 (validate: GSE73754, = 72; best AUC 0.861), while Round 2 (validate: GSE25101, = 32) yielded more modest performance (best AUC, 0.715) reflecting the smaller validation sample. Exploratory application to GSE11886 (macrophage-derived samples) showed near-chance performance, consistent with the tissue-source discrepancy. AS patients exhibited significant downregulation of oxidative phosphorylation, TCA cycle, and glycolysis pathways ( < 0.01), accompanied by elevated glutathione metabolism ( < 0.001). Immune cell deconvolution revealed reduced CD8+ T cell proportions correlating with downregulation, and increased neutrophil frequencies correlating with upregulation. Exploratory single-cell analysis indicated that expression was relatively enriched in border-associated macrophages and fibroblasts, while was more prominently expressed in vascular endothelial cells and plasmacytoid dendritic cells. The ceRNA network identified 21 miRNAs and 65 lncRNAs forming 86 regulatory interactions, with four key regulatory axes (SATB1-AS1/miR-539-5p/, FAM95B1/miR-223-3p/, LINC01106/miR-106a-5p/, AATBC/miR-185-5p/) predicted to regulate hub gene expression. Compound screening identified betaine, pyruvic acid, citric acid, etc., as top-ranking candidates, with showing the highest binding capacity among hub genes. This study provides an integrative framework linking metabolic reprogramming with immune dysfunction in AS. The six-gene diagnostic signature showed preliminary discriminatory ability in the available datasets, while the ceRNA regulatory network and natural compound screening results prioritize candidate regulatory pathways and compounds for future validation. These findings advance our understanding of AS pathogenesis and may guide future biomarker development and targeted intervention strategies. - Source: PubMed
Publication date: 2026/04/27
Dan XuejianGuan XiangyuanHu HangjianLiu WeiWu ZhouruiHu XiaoXu WeiZhao YunfeiMa Bin - Pancreatic ductal adenocarcinoma (PDAC) is characterized by frequent SMAD4 inactivation and extensive lipid metabolic rewiring, yet the mechanistic crosstalk between these processes remains poorly elucidated. - Source: PubMed
Publication date: 2026/04/12
Wang YangZhang ShanSong YiranAn LiweiZhao ZhangtingZhou YingqunWang Feng - Life expectancy has steadily increased in the last two centuries, while healthspan has been lagging behind. Survival into extreme ages strongly clusters within families which often exhibit a delayed onset of (multi)morbidity, yet the underlying protective genetic mechanisms are still largely undefined. We performed affected sib-pair linkage analysis in 212 sibships enriched for ancestral longevity and identified four genomic regions (LOD ≥3.0) at ., and . Within these regions, we prioritized 12 rare protein-altering variants in seven candidate genes ( and ) located in longevity-associated loci. Notably, a missense variant in (rs200818241), was present in two sibships. Using human- and mouse-based cell models, we showed that rs200818241 reduced protein stability and attenuated activation of the canonical cGAS-STING pathway in a cell-type specific manner. This dampened signalling mitigated inflammation and delayed cellular senescence, mechanisms that may contribute to the survival advantage of variant carriers. Our findings indicate novel rare variants and candidate genes linked to familial longevity and highlight the cGAS-STING pathway as a potential contributor to the protective mechanisms underlying human longevity. - Source: PubMed
Publication date: 2025/12/08
Putter Pasquale CGuan DiGehrmann ThiesKolbe DanielYang JipingHan HyeRimKim SeungsooLakenberg NicoSuchiman H Eka DTrompet StellaLiu Georg CBallhysa EugenAntebi Adamvan den Berg Niels M ANebel AlmutBeekman MarianSuh YousinSlagboom P ElineDeelen Joris - Inborn errors of metabolism (IEMs) lead to early-onset neurodegenerative disorders often caused by mitochondrial dysfunction. In this study, we identified a homozygous frameshift mutation (c.283dupG; p.Cys65LeufsTer13) in SLC27A3, identified through exome sequencing in a 2-month-old female proband presenting with developmental regression, hypotonia, seizure, feeding difficulty, and bilateral putaminal lesions on brain magnetic resonance imaging (MRI). The mutation results in a truncated, non-functional protein and complete loss of SLC27A3 expression in proband-derived fibroblasts. Results show the absence of SLC27A3 and aberrant mitochondrial morphology with clumped networks. Metabolic profiling showed elevated acyl-carnitine levels in the cytosol of proband cells, indicative of disrupted fatty acid oxidation. Additionally, mitochondrial respiratory chain activity was significantly reduced, and flow cytometry revealed increased cell death in mutant cells compared to controls. Protein-protein interaction analysis revealed SLC27A3 networks linked to fatty acid metabolism, ER-associated degradation (ERAD), and ion transport. GO enrichment demonstrated strong associations with transporter activity, protein homeostasis, and ER-mitochondrial membrane networks. Regional expression profiling showed high SLC27A3 transcript levels in the basal ganglia, correlating with the observed neuropathology. These findings position SLC27A3 as a critical lipid transporter involved in neuronal energy metabolism and proteostasis, and implicate its loss in mitochondrial encephalopathy. This study expands the genotypic and phenotypic spectrum of metabolic neurodevelopmental disorders and highlights the importance of fatty acid transport proteins in mitochondrial health and brain development. Our findings propose SLC27A3 as a novel candidate gene for early-onset mitochondrial disorders. - Source: PubMed
Publication date: 2025/11/25
Rehan Ahmad SNasir NazimKumari AnupriyaUl Hassan Atiq