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dc.contributor.authorJersin, Regine Å.
dc.contributor.authorTallapragada, Divya Sri Priyanka
dc.contributor.authorMadsen, André
dc.contributor.authorSkartveit, Linn
dc.contributor.authorFjære, Even
dc.contributor.authorMcCann, Adrian
dc.contributor.authorDyer, Laurence
dc.contributor.authorWillems, Aron
dc.contributor.authorBjune, Jan-Inge
dc.contributor.authorBjune, Mona S.
dc.contributor.authorVåge, Villy
dc.contributor.authorNielsen, Hans Jørgen
dc.contributor.authorThorsen, Håvard Luong
dc.contributor.authorNedrebø, Bjørn Gunnar
dc.contributor.authorBusch, Christian
dc.contributor.authorSteen, Vidar M.
dc.contributor.authorBlüher, Matthias
dc.contributor.authorJacobson, Peter
dc.contributor.authorSvensson, Per-Arne
dc.contributor.authorFernø, Johan
dc.contributor.authorRydén, Mikael
dc.contributor.authorArner, Peter
dc.contributor.authorNygård, Ottar
dc.contributor.authorClaussnitzer, Melina
dc.contributor.authorEllingsen, Ståle
dc.contributor.authorMadsen, Lise
dc.contributor.authorSagen, Jørn V.
dc.contributor.authorMellgren, Gunnar
dc.contributor.authorDankel, Simon N
dc.date.accessioned2021-06-24T09:07:32Z
dc.date.available2021-06-24T09:07:32Z
dc.date.created2021-01-29T15:28:44Z
dc.date.issued2021
dc.identifier.issn0012-1797
dc.identifier.urihttps://hdl.handle.net/11250/2761061
dc.description.abstractElucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.en_US
dc.language.isoengen_US
dc.publisherAmerican Diabetes Associationen_US
dc.titleRole of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity and Insulin Resistanceen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionacceptedVersionen_US
dc.rights.holder© 2021 by the American Diabetes Associationen_US
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.fulltextpostprint
cristin.qualitycode2
dc.identifier.doi10.2337/db20-0096
dc.identifier.cristin1882710
dc.source.journalDiabetesen_US
dc.source.pagenumber680-695en_US
dc.identifier.citationDiabetes. 2021, 70 (3), 680-695.en_US
dc.source.volume70en_US
dc.source.issue3en_US


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