Human adipose tissue gene expression of solute carrier family 19 member 3 (<i>SLC19A3</i>); relation to obesity and weight‐loss

Pereira, Maria J.; Andersson‐Assarsson, Johanna C.; Jacobson, Peter; Kamble, Prasad G.; Taube, Magdalena; Sjöholm, Kajsa; Carlsson, Lena; Svensson, Per‐Arne

doi:10.1002/osp4.541

Cited by 5 publications

(5 citation statements)

References 31 publications

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“…S1a-b). An RNAseq-based screen identified ThTr2 as adipose tissue-specific; its highest expression in this tissue dominantly correlated with the expression of mitochondrial genes pointing to a possible link between the presence of ThTr2 and brown/beige adipocytes (Pereira et al, 2021). Analysis of RNAseq data of Perdikari et al (2018) reveals that ThTr2 expression is higher than ThTr1 expression (estimated by mRNA counts) in both human WAT and BAT obtained by needle biopsies from the neck area (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous study revealed that ThTr2 expression was lower in neck fat derived adipocytes isolated from individuals carrying FTO rs1421085 obesity risk alleles CC compared to healthy alleles TT [12]. A recent report demonstrated that SC adipose tissue isolated from individuals with obesity expressed lower ThTr2 as compared to lean individuals and the expression of ThTr2 positively correlated with weight loss [30] suggesting its possible role in augmentation of energy metabolism. Thiamine supplementation prevented obesity and obesity-associated metabolic disorders in OLETF rats [65].…”

Section: Discussionmentioning

confidence: 99%

“…The high affinity ThTr2 (ThTr2 has an influx constant Kt of 25 nM while ThTr1 works at 2.5 μM) (Manzetti et al, 2018) can play a more pronounced role than ThTr1 in the continuous uptake of thiamine during the thermogenic response of adipocytes since its expression level was found to be higher in potentially thermogenic adipocytes (Fig. 1) (Perdikari et al, 2018; Min et al, 2019; Pereira et al, 2021) and its inhibitor fedratinib could significantly decrease respiration in stimulated adipocytes. We could validate the expression pattern of ThTrs at protein level in human SC and DN adipose tissue biopsies as well where fedratinib could inhibit UCP1 induction by adrenergic stimulation.…”

Section: Discussionmentioning

confidence: 99%

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Availability of abundant thiamine determines efficiency of thermogenic activation in human neck area derived adipocytes

Arianti

Vinnai

Győry

et al. 2022

Preprint

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Objective: Brown/beige adipocytes are characterized by expression of uncoupling protein-1 (UCP1) that enables them to dissipate energy as heat instead of generating ATP. The activation of this process can alleviate obesity as it augments energy expenditure. Human brown adipose tissue is interspersed in distinct anatomical regions including the deep neck area. We found that UCP1 enriched adipocytes differentiated from progenitors of this depot highly expressed ThTr2 transporter of thiamine, the precursor of thiamine pyrophosphate (TPP) cofactor for mitochondrial fuel generating enzymes, and aimed to investigate the importance of thiamine availability during thermogenic activation. Methods: Human adipocytes were differentiated from subcutaneous and deep neck precursors and activated for thermogenesis by the cell permeable dibutyryl-cAMP, which mimics adrenergic stimulation. Proton leak respiration reflecting heat generation was monitored by Seahorse XF analyzer. Direct mitochondrial effect of TPP was observed in flux assay of permeabilized adipocytes. Expression of thermogenic genes and proteins was analyzed by RT-qPCR and immunoblotting, respectively. Results: Inhibition of ThTr2 during thermogenic activation of deep and subcutaneous neck derived adipocytes by cAMP led to decreased proton leak respiration reflecting lower uncoupling activity. In the absence of thiamine, cAMP-induced elevation of proton leak respiration was diminished but restored by thiamine addition reaching highest levels in deep neck adipocytes and at concentrations larger than present in human blood plasma. Addition of TPP to permeabilized adipocytes increased proton leak respiration fueled by one of the TPP-dependent enzymes, pyruvate dehydrogenase. ThTr2 inhibition also hampered cAMP-dependent induction of UCP1, PGC1a and other browning marker genes, along with mitochondrial complex subunits, and thermogenic induction of these genes was potentiated by thiamine in a concentration dependent manner. Conclusion: Our study has revealed the importance of amply supplied thiamine during thermogenic activation in human adipocytes. Thiamine may increase heat generation by providing TPP for TPP-dependent enzymes which lack this cofactor and by potentiating the induction of UCP1 and other thermogenic genes.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Availability of abundant thiamine determines efficiency of thermogenic activation in human neck area derived adipocytes

Arianti

Vinnai

Győry

et al. 2022

Preprint

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“…It should be noted that there were some DEGs that were not shared among IPF networks, but have been proven to play indispensable roles in IPF in recent years. Involvement of highly significant DEGs [131], SLC7A11 [132], CLIC5 [133], VIP (vasoactive intestinal peptide) [134], SMAD6 [135], BMPR2 [136], APOA1 [137], IN-SIG1 [138], TLR3 [139], NLRP12 [140], ADRB1 [141], TLR8 [142], GATA3 [143], CCR2 [144], TLR7 [145], CCRL2 [146], BMPER (BMP binding endothelial regulator) [147], CAV1 [148], TFPI (tissue factor pathway inhibitor) [149], FADS1 [150], SUCNR1 [151], CADM2 [152], SLC19A3 [153], SGCG (sarcoglycan gamma) [154] [177], WNT3A [178], APOH (apolipoprotein H) [179], CHRM3 [180], CD36 [181], TRIB3 [182], PCSK9 [183], ACVR1C [184], GPD1 [123], FFAR4 [185], GPX3 [186], FGF2 [187], FASN (fatty acid synthase) [188], DGAT2 [189], DACH1 [190], PNPLA3 [191], FGF9 [192], SLC7A11 [193], VIP (vasoactive intestinal peptide) [194], KL (klotho)…”

Section: Discussionmentioning

confidence: 99%

Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis

Giriyappagoudar,

Vastrad,

Horakeri

et al. 2023

Biomedicines

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Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with reduced quality of life and earlier mortality, but its pathogenesis and key genes are still unclear. In this investigation, bioinformatics was used to deeply analyze the pathogenesis of IPF and related key genes, so as to investigate the potential molecular pathogenesis of IPF and provide guidance for clinical treatment. Next-generation sequencing dataset GSE213001 was obtained from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) were identified between IPF and normal control group. The DEGs between IPF and normal control group were screened with the DESeq2 package of R language. The Gene Ontology (GO) and REACTOME pathway enrichment analyses of the DEGs were performed. Using the g:Profiler, the function and pathway enrichment analyses of DEGs were performed. Then, a protein–protein interaction (PPI) network was constructed via the Integrated Interactions Database (IID) database. Cytoscape with Network Analyzer was used to identify the hub genes. miRNet and NetworkAnalyst databaseswereused to construct the targeted microRNAs (miRNAs), transcription factors (TFs), and small drug molecules. Finally, receiver operating characteristic (ROC) curve analysis was used to validate the hub genes. A total of 958 DEGs were screened out in this study, including 479 up regulated genes and 479 down regulated genes. Most of the DEGs were significantly enriched in response to stimulus, GPCR ligand binding, microtubule-based process, and defective GALNT3 causes HFTC. In combination with the results of the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network, hub genes including LRRK2, BMI1, EBP, MNDA, KBTBD7, KRT15, OTX1, TEKT4, SPAG8, and EFHC2 were selected. Cyclothiazide and rotigotinethe are predicted small drug molecules for IPF treatment. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of IPF, and provide a novel strategy for clinical therapy.

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“…Signaling pathways include GPCR ligand binding [89], neutrophil degranulation [90], immune system [91], metabolism of lipids [92] and signal transduction [93] made great contribution to the development of IPF. MAP3K15 [94], PRTN3 [95], CX3CR1 [96], AGRP (agouti related neuropeptide) [97], MPO (myeloperoxidase) [98], CD5L [99], S100A8 [100], NPR3 [101], VEGFD (vascular endothelial growth factor D) [102], CXCL11 [103], IL1A [104], CBS (cystathionine beta-synthase) [105], WNT7A [106], SCD (stearoyl-CoA desaturase) [107], LRP2 [108], SLC6A4 [109], BDNF (brain derived neurotrophic factor) [110], CXCL10 [111], ANGPTL7 [112], S100A9 [113], NPY1R [114], IL1B [115], GPIHBP1 [116], CYP1B1 [117], CD36 [118], MACROD2 [119], TRIB3 [120], SPX (spexin hormone) [121], PCSK9 [122], GPD1 [123], CDH13 [124], FFAR4 [125], FGF2 [126], FASN (fatty acid synthase) [127], DGAT2 [128], DACH1 [129], PNPLA3 [130], FGF9 [131], SLC7A11 [132], CLIC5 [133], VIP (vasoactive intestinal peptide) [134], SMAD6 [135], BMPR2 [136], APOA1 [137], INSIG1 [138], TLR3 [139], NLRP12 [140], ADRB1 [141], TLR8 [142], GATA3 [143], CCR2 [144], TLR7 [145], CCRL2 [146], BMPER (BMP binding endothelial regulator) [147], CAV1 [148], TFPI (tissue factor pathway inhibitor) [149], FADS1 [150], SUCNR1 [151], CADM2 [152], SLC19A3 [153], SGCG (sarcoglycan gamma) [154], ADH1B [155], NEGR1 [156], HSD17B12 [157], OXTR (oxytocin receptor) [158] and ANKK1 […”

Section: Discussionmentioning

confidence: 99%

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2023

Preprint

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with reduced quality of life and earlier mortality, but its pathogenesis and key genes are still unclear. In this investigation, bioinformatics was used to deeply analyze the pathogenesis of IPF and related key genes, so as to investigate the potential molecular pathogenesis of IPF and provide guidance for clinical treatment. Next generation sequencing dataset GSE213001 was obtained from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were identified between IPF and normal control group. The DEGs between IPF and normal control group were screened with the DESeq2 package of R language. The Gene Ontology (GO) and REACTOME pathway enrichment analyses of the DEGs were performed. Using the g:Profiler, the function and pathway enrichment analysis of DEGs were performed. Then, a protein protein interaction (PPI) network was constructed via the Integrated Interactions Database (IID) database. Cytoscape with Network Analyzer was used to identify the hub genes. miRNet and NetworkAnalyst database was used to construct the targeted microRNAs (miRNAs) and transcription factors (TFs) of the hub genes. Finally receiver operating characteristic (ROC) curve analysis was used to validates the hub genes. A total of 958 DEGs were screened out in this study, including 479 up regulated genes and 479 down regulated genes. Most of the DEGs were significantly enriched in response to stimulus, GPCR ligand binding, microtubule-based process and defective GALNT3 causes HFTC. In combination with the results of the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network, hub genes including LRRK2, BMI1, EBP, MNDA, KBTBD7, KRT15, OTX1, TEKT4, SPAG8 and EFHC2 were selected. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of IPF, and provide a novel strategy for clinical therapy.

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Human adipose tissue gene expression of solute carrier family 19 member 3 (SLC19A3); relation to obesity and weight‐loss

Cited by 5 publications

References 31 publications

Availability of abundant thiamine determines efficiency of thermogenic activation in human neck area derived adipocytes

Availability of abundant thiamine determines efficiency of thermogenic activation in human neck area derived adipocytes

Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

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