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

Takuro Nagoya; Kenya Kamimura; Ryo Goto; Yoko Shinagawa-Kobayashi; Yusuke Niwa; Atsushi Kimura; Norihiro Sakai; Masayoshi Ko; Hiroshi Nishina; Shuji Terai

doi:10.1002/2211-5463.12734

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.

Authors

Affiliations

¹ Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan.
² Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, Japan.

Abstract

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

Substances

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