The role of SLC transporters in metabolic diseases

Solute Carrier (SLC) transporters mediate the transport of metabolically active carboxylates across membranes. Some of them have been linked to metabolic diseases, such as obesity and type 2 diabetes and some have already been identified as successful drug targets to treat these diseases.

We have recently identified the sodium-coupled citrate plasma membrane transporter INDY (I’m Not Dead Yet, SLC13A5) as a potential target to treat metabolic diseases. INDY is primarily expressed in metabolically active organs, providing cells with citrate and other dicarboxylates. The genetic knockout of the protein-coding gene mIndy has been found to protect various organisms from diet-induced obesity and insulin resistance as well as non-alcoholic fatty liver disease and to promote longevity. We are currently testing if the pharmacological inhibition of the transporter can mimic these promising results.

Quelle: modified from Birkenfeld et al, Cellular Metabolism (2011)

Main objectives

  • Elucidate the role of different SLC transporters in metabolic disease.
  • Investigate the effect of pharmacologic inhibition of SLC13A5 (INDY) in diabetes and NASH.

Project Supervisor

Prof. Dr. Andreas L. Birkenfeld and Dr. Anica Kurzbach

Project-related publications

Willmes, D. M. et al. The longevity gene mIndy (I'm Not Dead, Yet) affects blood pressure through sympathoadrenal mechanisms. JCI Insight 6, doi:10.1172/jci.insight.136083 (2021)

Henke, C. et al. Disruption of the sodium-dependent citrate transporter SLC13A5 in mice causes alterations in brain citrate levels and neuronal network excitability in the hippocampus. Neurobiol Dis 143, 105018, doi:10.1016/j.nbd.2020.105018 (2020)

Schumann, T. et al. Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease. Pharmacol Rev 72, 343-379, doi:10.1124/pr.118.015735 (2020)

von Loeffelholz, C. et al. The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism. Hepatology 66, 616-630, doi:10.1002/hep.29089 (2017)

Birkenfeld, A. L. et al. Deletion of the mammalian INDY homolog mimics aspects of dietary restriction and protects against adiposity and insulin resistance in mice. Cell Metab 14, 184-195, doi:10.1016/j.cmet.2011.06.009 (2011)