Sodium glucose co-transporter 2 inhibitor ameliorates autophagic flux impairment on renal proximal tubular cells in obesity mice

Kazuhiko Fukushima, Shinji Kitamura, Kenji Tsuji, Yizhen Sang, Jun Wada

Research output: Contribution to journalArticle

Abstract

Obesity is supposed to cause renal injury via autophagy deficiency. Recently, sodium glucose co-transporter 2 inhibitors (SGLT2i) were reported to protect renal injury. However, the mechanisms of SGLT2i for renal protection are unclear. Here, we investigated the effect of SGLT2i for autophagy in renal proximal tubular cells (PTCs) on obesity mice. We fed C57BL/6J mice with a normal diet (ND) or high-fat and-sugar diet (HFSD) for nine weeks, then administered SGLT2i, empagliflozin, or control compound for one week. Each group contained N = 5. The urinary N-acetyl-beta-d-glucosaminidase level in the HFSD group significantly increased compared to ND group. The tubular damage was suppressed in the SGLT2i–HFSD group. In electron microscopic analysis, multi lamellar bodies that increased in autophagy deficiency were increased in PTCs in the HFSD group but significantly suppressed in the SGLT2i group. The autophagosomes of damaged mitochondria in PTCs in the HFSD group frequently appeared in the SGLT2i group. p62 accumulations in PTCs were significantly increased in HFSD group but significantly suppressed by SGLT2i. In addition, the mammalian target of rapamycin was activated in the HFSD group but significantly suppressed in SGLT2i group. These data suggest that SGLT2i has renal protective effects against obesity via improving autophagy flux impairment in PTCs on a HFSD.

Original languageEnglish
Article number4054
Pages (from-to)1-14
Number of pages14
JournalInternational journal of molecular sciences
Volume21
Issue number11
DOIs
Publication statusPublished - Jun 1 2020
Externally publishedYes

Keywords

  • Autophagy
  • Mammalian target of rapamycin (mTOR)
  • Multi lamellar body
  • Obesity
  • Sodium glucose co-transporter 2 inhibitor

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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