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Deletion of the diabetes candidate gene Slc16a13 in mice attenuates diet-induced ectopic lipid accumulation and insulin resistance

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Tina Schumann, Jörg König, Christian von Loeffelholz, Daniel F. Vatner, Dongyan Zhang, Rachel J. Perry, Michel Bernier, Jason Chami, Christine Henke, Anica Kurzbach, Nermeen N. El-Agroudy, Diana M. Willmes, Dominik Pesta, Rafael de Cabo, John F. O´Sullivan, Eric Simon, Gerald I. Shulman, Bradford S. Hamilton, Andreas L. Birkenfeld

Original languageEnglish
Article number826
JournalCommunications Biology
Issue number1
PublishedDec 2021

Bibliographical note

Funding Information: We thank Doreen Ussath, Julia Paditz, Stephan Friebe, and David Arturo Juárez López for excellent technical assistance. We thank Mario Kahn for the analysis of DAGs and ceramides, Werner Rust, and Dr. Tobias Hildebrandt for conducting the next-generation sequencing and Taconic Biosciences for the generation of Slc16a13 knockout mice. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—BI 1292/10-1 and the Deutsche Diabetes Gesellschaft (DDG, German Diabetes Association) as well as an unrestricted grant from Boehringer Ingelheim Pharma GmbH & Co. KG. This work was also supported, in part, by the Intramural Research Program of the National Institute on Aging, NIH. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


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 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.

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