Schumann, Tina, Koenig, Joerg, von Loeffelholz, Christian, Vatner, Daniel F., Zhang, Dongyan, Perry, Rachel J., Bernier, Michel ORCID: 0000-0002-5948-368X, Chami, Jason ORCID: 0000-0002-1683-2800, Henke, Christine, Kurzbach, Anica, El-Agroudy, Nermeen N., Willmes, Diana M., Pesta, Dominik, de Cabo, Rafael, Sullivan, John F. O., Simon, Eric, Shulman, Gerald, I, 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. Commun. Biol., 4 (1). BERLIN: NATURE RESEARCH. ISSN 2399-3642

Full text not available from this repository.

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 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-PKC epsilon 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. Schumann et al. demonstrate that the loss of a lactate transporter Slc16a13 increases mitochondrial respiration in the liver, which reduces hepatic lipid accumulation while increasing hepatic insulin sensitivity in mice fed a high-fat diet. This study suggests SLC16A13 as a potential target for the treatment of type 2 diabetes and non-alcoholic fatty liver disease.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schumann, TinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koenig, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Loeffelholz, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vatner, Daniel F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, DongyanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perry, Rachel J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bernier, MichelUNSPECIFIEDorcid.org/0000-0002-5948-368XUNSPECIFIED
Chami, JasonUNSPECIFIEDorcid.org/0000-0002-1683-2800UNSPECIFIED
Henke, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurzbach, AnicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
El-Agroudy, Nermeen N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Willmes, Diana M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pesta, DominikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Cabo, RafaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sullivan, John F. O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simon, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shulman, Gerald, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamilton, Bradford S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Birkenfeld, Andreas L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-604510
DOI: 10.1038/s42003-021-02279-8
Journal or Publication Title: Commun. Biol.
Volume: 4
Number: 1
Date: 2021
Publisher: NATURE RESEARCH
Place of Publication: BERLIN
ISSN: 2399-3642
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FATTY LIVER-DISEASE; INDUCED HEPATIC STEATOSIS; MONOCARBOXYLATE TRANSPORTER-1; TYPE-2; VARIANTS; LACTATE; OBESITY; ASSOCIATION; ACTIVATION; FAMILYMultiple languages
Biology; Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60451

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item