nam 22 uu 4500 dbt_mods_00056574 10.1038/s42003-021-02279-8 doi dbt_mods_00056574 ger DE-601 rda eng 610 sdnb Schumann, Tina Author aut German Center for Diabetes Research (DZD), Neuherberg, Germany Deletion of the diabetes candidate gene Slc16a13 in mice attenuates diet-induced ectopic lipid accumulation and insulin resistance Schumann, Tina;König, Jörg;von Loeffelholz, Christian;Vatner, Daniel F.;Zhang, Dongyan;Perry, Rachel J.;Bernier, Michel;Chami, Jason;Henke, Christine;Kurzbach, Anica;El-Agroudy, Nermeen N.;Willmes, Diana M.;Pesta, Dominik;de Cabo, Rafael;O´Sullivan, John F.;Simon, Eric;Shulman, Gerald I.;Hamilton, Bradford S.;Birkenfeld, Andreas L. 2021-07-01 17 Seiten text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Zweitveröffentlichung Abstract Genome-wide association studies have identified SLC16A13 as a novel susceptibility gene for type 2 diabetes. The SLC16A13 gene encodes SLC16A13/MCT13, a member of the solute carrier 16 family of monocarboxylate transporters. Despite its potential importance to diabetes development, the physiological function of SLC16A13 is unknown. Here, we validate Slc16a13 as a lactate transporter expressed at the plasma membrane and report on the effect of Slc16a13 deletion in a mouse model. We show that loss of Slc16a13 increases mitochondrial respiration in the liver, leading to reduced hepatic lipid accumulation and increased hepatic insulin sensitivity in high-fat diet fed Slc16a13 knockout mice. We propose a mechanism for improved hepatic insulin sensitivity in the context of Slc16a13 deficiency in which reduced intrahepatocellular lactate availability drives increased AMPK activation and increased mitochondrial respiration, while reducing hepatic lipid content. Slc16a13 deficiency thereby attenuates hepatic diacylglycerol-PKCε mediated insulin resistance in obese mice. Together, these data suggest that SLC16A13 is a potential target for the treatment of type 2 diabetes and non-alcoholic fatty liver disease. Animal disease models Fat metabolism Non-alcoholic fatty liver disease Type 2 diabetes article König, Jörg Author aut Clinical Pharmacology and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany von Loeffelholz, Christian Author aut Department of Anaesthesiology and Intensive Care, Jena University Hospital, Jena, Germany (DE-588)12444086X Vatner, Daniel F. Author aut Department of Internal Medicine, Yale School of Medicine, New Haven, USA Zhang, Dongyan Author aut Department of Internal Medicine, Yale School of Medicine, New Haven, USA Perry, Rachel J. Author aut Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, USA Bernier, Michel Author aut Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, USA Chami, Jason Author aut Heart Research Institute, Newtown, Australia Henke, Christine Author aut German Center for Diabetes Research (DZD), Neuherberg, Germany Kurzbach, Anica Author aut German Center for Diabetes Research (DZD), Neuherberg, Germany El-Agroudy, Nermeen N. Author aut German Center for Diabetes Research (DZD), Neuherberg, Germany Willmes, Diana M. Author aut German Center for Diabetes Research (DZD), Neuherberg, Germany Pesta, Dominik Author aut German Center for Diabetes Research (DZD), Neuherberg, Germany de Cabo, Rafael Author aut Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, USA O´Sullivan, John F. Author aut Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, Australia Simon, Eric Author aut Computational Biology, Boehringer-Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany Shulman, Gerald I. Author aut Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, USA Hamilton, Bradford S. Author aut CardioMetabolic Diseases Research, Boehringer-Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany Birkenfeld, Andreas L. Author aut Department of Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany Friedrich-Schiller-Universität Jena Medizinische Fakultät host institution his 4:1:826 Communications Biology 2399-3642 dbt_mods_00056573 https://www.db-thueringen.de/receive/dbt_mods_00056574 object in context https://www.db-thueringen.de/servlets/MCRFileNodeServlet/dbt_derivate_00059549/s42003-021-02279-8.pdf raw object https://www.db-thueringen.de/rsc/thumbnail/dbt_mods_00056574.png preview https://www.db-thueringen.de/receive/dbt_mods_00056574 uri