{"database": "metadata", "table": "run_metadata", "rows": [[53267, "SRR9735183", "SRX6492143", "SRS5140739", "SRP216059", "PRJNA556239", "Adipocyte serine uptake curbs ROS generation and visceral adiposity [Zebrafish]", "GSE134733", "Transcriptome Analysis", "Obesity  and visceral adiposity in particular  increases the risk of common metabolic diseases  including type 2 diabetes  cardiovascular disease  and several forms of cancer. However  the molecular mechanisms responsible for regional fat storage remain poorly characterized  preventing therapeutic innovation. We here applied a systematic genome wide screen and translational approach  and discovered a novel role for the adipocyte expressed neutral amino acid transporter SLC7A10/ASC 1 in the regulation of visceral adiposity. Among 65 genes showing both adipose depot dependent and fat loss dependent expression  27 genes further showed significant correlations with waist to hip WHR ratio adjusted for BMI. Among these ASC 1 was expressed at the highest level in isolated visceral adipocytes. Further  we found decreased ASC 1 mRNA in visceral  and not subcutaneous adipose tissue  in carriers of the KLF14 type 2 diabetes risk allele compared to the protective allele. By profiling amino acid fluxes during adipocyte differentiation in vitro  we found that ASC 1 inhibition by a selective inhibitor decreased adipocyte uptake particularly of serine in mature adipocytes. Interestingly  radiometric amino acid uptake assays showed ASC 1 dependent uptake of the serine D enantiomere. Using primary human and murine adipocyte models  we uncovered marked effects of inhibiting ASC 1 on mitochondrial respiratory capacity within hours and lipid accumulation within days. Finally  Asc 1 knockout KO zebrafish had increased body weight and adipocyte enlargement upon eight week overfeeding compared to wild type WT fish. RNA sequencing data from zebrafish adipose tissue showed up regulation of genes involved in fatty acid and lipid metabolism in the ASC 1 KOs  consistent with the increased lipid accumulation in the inhibitor treated cell models. Additionally  duox  an enzyme involved in ROS generation  showed higher expression in the KOs compared to the WTs. Importantly  we confirmed increased reactive oxygen species ROS generation within minutes and within hours when inhibiting ASC 1 in our in vitro cell models. Our study points to increased ROS generation and reduced mitochondrial respiratory capacity as central early mechanisms in development of visceral adiposity  and a role for adipocyte D serine transport via ASC 1 in these processes. Enhancing ASC 1 expression and/or activity in adipocytes  likely through primary effects on one carbon metabolism and redox balance  is a promising therapeutic strategy for reducing visceral adiposity and related diseases. Overall design: Total RNA Seq of Zebrafish adipose tissue were sequenced on the Illumina HiSeq4000 platform", "parent bioproject:PRJNA557596", null, null, "Adipose KO A4", "GSM3964272", null, "source name:Adipose|genotype:ASC 1 KO|age:6 month|tissue:Adipose", "Adipose KO A4", "Illumina Casava v1.8 Reads were aligned to the Zebrafish reference genome GRCz10 using HiSat Version 2.05  with options \u201chisat2 align s   wrapper basic 0  p 140\u201d Aligned reads were then put into featureCounts Version 1.5.2 with options \u201cfeatureCounts  T 64  p  t exon  g gene id\u201d Differential expression analysis was performed via DESeq2 Version 1.14.1 Genome build: GRCz10 Supplementary files format and content: tab delimited text files include DESeq2 normalised counts for each Sample ...", "Adipose", "Individuals were overfed for a period of 2 month on GEMMA Micro 500 Skretting  USA 3 times per day and given 3 drops of freshly hatched Artemia once per day.", "Tissue biopsies from three fish in each tank were pooled together  snap frozen and processed for kit based extraction of RNA  using the RNeasy kit QIAGEN  and quality checked via spectrophotometer. RNA libraries were prepared for sequencing using standard Illumina protocols", "Zebrafish were housed in 3 litre tanks for a period of 4 month and subsequently housed for a further 2 month in 1.5 litre tanks with 3 individuals per tank.", "genotype:ASC 1 KO|age:6 month|tissue:Adipose", "GSM3964272", "GSM3964272: Adipose KO A4; Danio rerio; RNA Seq", "GSM3964272", null, "1", "Tissue biopsies from three fish in each tank were pooled together  snap frozen and processed for kit based extraction of RNA  using the RNeasy kit QIAGEN  and quality checked via spectrophotometer. RNA libraries were prepared for sequencing using standard Illumina protocols", "GEO Accession:GSM3964272", "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "ILLUMINA", "Illumina HiSeq 4000", null, "SRP216059", null, null, "KO-A4_S58_R1_001.fastq KO-A4_S58_R2_001.fastq", "fastq fastq", 6392993509.0, 42397316.0, "GSM3964272 r1", "0:75.43 1:75.36", "A:1675757830;C:1504320009;G:1478667713;T:1726331052;N:7916905", 75, 75, null, null, 1675757830, 1504320009, 1478667713, 1726331052, 7916905, "SRX6492143", "SRS5140739", "SRA925242", "GEO", "Hormone Laboratory, Clinical Institute, University of Bergen", 2, 0.93219, 0.93293, 0.07772, 0.07734, 0.63782, 0.64193, 0.4886, 0.49125, 75, 76, "B", "B", "biological fallback assumption", "illumina", "hiseq_era", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Norway", "2019-07-23", "Adult", "Adult", "Adipose Tissue", "Adipose Tissue"]], "columns": ["rowid", "run.accession", "experiment.accession", "sample.accession", "study.accession", "bioproject", "study.title", "study.alias", "study.type", "study.abstract", "study.attributes", "study.PMIDs", "sample.description", "sample.title", "sample.alias", "sample.centername", "sample.attributes", "GEOsample.title", "GEOsample.dataprocessing", "GEOsample.source", "GEOsample.treatmentprotocol", "GEOsample.extractprotocol", "GEOsample.growthprotocol", "GEOsample.characteristics", "GEOsample.accession", "experiment.title", "experiment.alias", "experiment.library_name", "experiment.design_description", "experiment.library_construction_protocol", "experiment.attributes", "experiment.library_strategy", "experiment.library_source", "experiment.library_selection", "experiment.library_layout", "experiment.platform", "experiment.instrument_model", "experiment.spot_descriptor", "experiment.study_ref", "run.title", "run.attributes", "run.filename", "run.semantic_name", "run.total_bases", "run.total_spots", "run.alias", "run.read_lengths", "run.base_counts", "run.r1_length", "run.r2_length", "run.r3_length", "run.r4_length", "run.Acount", "run.Ccount", "run.Gcount", "run.Tcount", "run.Ncount", "run.experiment", "run.pool_member", "submission.accession", "submission.srasource", "submission.bioprojectsource", "seqdetective.n_mates", "seqdetective.mapping_rate.mate1", "seqdetective.mapping_rate.mate2", "seqdetective.nofeature_rate.mate1", "seqdetective.nofeature_rate.mate2", "seqdetective.sparsity.mate1", "seqdetective.sparsity.mate2", "seqdetective.pos_strand_rate.mate1", "seqdetective.pos_strand_rate.mate2", "seqdetective.readlen.mate1", "seqdetective.readlen.mate2", "seqdetective.judgement.mate1", "seqdetective.judgement.mate2", "seqdetective.judgement.reason", "platform_family", "instrument_generation", "read_bias", "selection_class", "prep_kit", "sc_or_bulk", "tech_class", "technology", "tech_variant", "submission.bioprojectsource.country", "earliest_date", "devstage_curation", "devstage_curation_coarse", "tissue_curation", "tissue_curation_coarse"], "primary_keys": ["rowid"], "primary_key_values": ["53267"], "units": {}, "query_ms": 10.33361900044838}