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

Schumann, Tina and König, Jörg and von Loeffelholz, Christian and Vatner, Daniel F. and Zhang, Dongyan and Perry, Rachel J. and Bernier, Michel and Chami, Jason and Henke, Christine and Kurzbach, Anica and El-Agroudy, Nermeen N. and Willmes, Diana M. and Pesta, Dominik and de Cabo, Rafael and Simon, Eric and O´Sullivan, John F. and Shulman, Gerald I. and Hamilton, Bradford S. and Birkenfeld, Andreas L. (2021) Deletion of the diabetes candidate gene Slc16a13 in mice attenuates diet-induced ectopic lipid accumulation and insulin resistance. Communications Biology, 4 (1), p. 826. Springer Nature. doi: 10.1038/s42003-021-02279-8. ISSN 2399-3642.

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Official URL: http://dx.doi.org/10.1038/s42003-021-02279-8

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.

Item URL in elib:https://elib.dlr.de/144662/
Document Type:Article
Title:Deletion of the diabetes candidate gene Slc16a13 in mice attenuates diet-induced ectopic lipid accumulation and insulin resistance
Authors:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iD
Schumann, TinaDresden University School of Medicine, Technische Universität DresdenUNSPECIFIED
König, JörgUNSPECIFIEDUNSPECIFIED
von Loeffelholz, ChristianUNSPECIFIEDUNSPECIFIED
Vatner, Daniel F.UNSPECIFIEDUNSPECIFIED
Zhang, DongyanUNSPECIFIEDUNSPECIFIED
Perry, Rachel J.UNSPECIFIEDUNSPECIFIED
Bernier, MichelUNSPECIFIEDUNSPECIFIED
Chami, JasonUNSPECIFIEDUNSPECIFIED
Henke, ChristineDresden University School of Medicine, Technische Universität DresdenUNSPECIFIED
Kurzbach, AnicaUniversity School of Medicine, Technische Universität DresdenUNSPECIFIED
El-Agroudy, Nermeen N.UNSPECIFIEDUNSPECIFIED
Willmes, Diana M.University Hospital Dresden, Dresden, GermanyUNSPECIFIED
Pesta, DominikInstitute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germanyhttps://orcid.org/0000-0002-5089-3586
de Cabo, RafaelUNSPECIFIEDUNSPECIFIED
Simon, EricUNSPECIFIEDUNSPECIFIED
O´Sullivan, John F.UNSPECIFIEDUNSPECIFIED
Shulman, Gerald I.UNSPECIFIEDUNSPECIFIED
Hamilton, Bradford S.UNSPECIFIEDUNSPECIFIED
Birkenfeld, Andreas L.University Hospital Carl-Gustav Carus, Dresden, GermanyUNSPECIFIED
Date:1 July 2021
Journal or Publication Title:Communications Biology
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:4
DOI :10.1038/s42003-021-02279-8
Page Range:p. 826
Publisher:Springer Nature
ISSN:2399-3642
Status:Published
Keywords:Type 2 diabetes, Fat metabolism, Animal disease models, Non-alcoholic fatty liver disease
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Research under Space Conditions
DLR - Research theme (Project):R - Bone metabolism and structural adaptation
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Muscle and Bone Metabolism
Deposited By: Schönenberg, Sandra
Deposited On:21 Oct 2021 17:21
Last Modified:21 Oct 2021 17:21

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