Inhibition of sodium-glucose cotransporter 2 ameliorates renal injury in a novel medaka model of nonalcoholic steatohepatitis-related kidney disease

FEBS Open Bio. 2019 Dec;9(12):2016-2024. doi: 10.1002/2211-5463.12734. Epub 2019 Nov 1.


The effect of sodium-glucose cotransporter 2 inhibitor (SGLT2I) on nonalcoholic steatohepatitis (NASH) has been reported, but there are few studies on its effect on NASH-related renal injury. In this study, we examined the effect of SGLT2I using a novel medaka fish model of NASH-related kidney disease, which was developed by feeding the d-rR/Tokyo strain a high-fat diet. SGLT2I was administered by dissolving it in water of the feeding tank. SGLT2I ameliorates macrophage accumulation and oxidative stress and maintained mitochondrial function in the kidney. The results demonstrate the effect of SGLT2I on NASH-related renal injury and the usefulness of this novel animal model for research into NASH-related complications.

Keywords: Oryzias latipes; NASH; SGLT2 inhibitor; kidney; medaka disease model; renal disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / pharmacology*
  • Diabetes Mellitus, Type 2
  • Diet, High-Fat
  • Disease Models, Animal
  • Glucose / metabolism
  • Glucosides / pharmacology*
  • Glutamate Plasma Membrane Transport Proteins / antagonists & inhibitors
  • Glutamate Plasma Membrane Transport Proteins / metabolism*
  • Glutamate Plasma Membrane Transport Proteins / physiology
  • Hypoglycemic Agents
  • Kidney / pathology
  • Kidney Diseases / metabolism*
  • Kidney Diseases / physiopathology
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Oryzias / metabolism
  • Sodium / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology


  • Benzhydryl Compounds
  • Glucosides
  • Glutamate Plasma Membrane Transport Proteins
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sodium
  • Glucose
  • 6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol