SGLT6 - A pharmacological target for the treatment of obesity?

Adipocyte. 2018;7(4):277-284. doi: 10.1080/21623945.2018.1516098. Epub 2018 Oct 11.

Abstract

Despite increased knowledge of nutrient intake regulation and energy homeostasis, treatment options for obesity remain limited. Food reward consists of two branches: gustatory and post-ingestive nutritive information. Drosophila lacking dSLC5A11 (sodium/glucose cotransporter 6-SGLT6) prefer L-glucose over D-glucose independently of their state of satiety. Human SGLT6 is an active transporter of myo-inositol and D-glucose. We investigated expression of SGLT6 in human tissue and found a significant expression in the small intestine and brain. The preference between a metabolizable and a non-metabolizable sugar was tested in 3 mouse models with a selective and potent SGLT6 inhibitor. No influence on sugar preference was seen with SGLT6 inhibition. These studies suggest that SGLT6 does not play a significant role in nutrient sensing in mammals.

Keywords: SGLT6; hunger; obesity; reward; sugar.

MeSH terms

  • Animals
  • Anti-Obesity Agents / pharmacokinetics
  • Anti-Obesity Agents / pharmacology*
  • Anti-Obesity Agents / therapeutic use
  • Caco-2 Cells
  • Food Preferences / drug effects
  • Glucose / metabolism
  • HEK293 Cells
  • Heat-Shock Proteins / antagonists & inhibitors*
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Inositol / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Targeted Therapy
  • Obesity / drug therapy*
  • Obesity / metabolism*
  • Symporters / antagonists & inhibitors*
  • Symporters / metabolism*

Substances

  • Anti-Obesity Agents
  • Heat-Shock Proteins
  • Symporters
  • SLC5A3 protein, human
  • Inositol
  • Glucose