Dehydrozingerone inhibits renal lipotoxicity in high-fat diet–induced obese mice

Eun Soo Lee, Jeong Suk Kang, Hong Min Kim, Su Jin Kim, Nami Kim, Jung Ok Lee, Hyeon Soo Kim, Eun Young Lee, Choon Hee Chung

Research output: Contribution to journalArticlepeer-review

Abstract

Ectopic fat accumulation in the kidneys causes oxidative stress, inflammation and cell death. Dehydrozingerone (DHZ) is a curcumin analog that exhibits antitumour, antioxidant and antidiabetic effects. However, the efficacy of DHZ in diabetic nephropathy (DN) is unknown. Here, we verified the efficacy of DHZ on DN. We divided the experimental animals into three groups: regular diet, 60% high-fat diet (HFD) and HFD with DHZ for 12 weeks. We analysed levels of renal triglycerides and urinary albumin and albumin-creatinine ratio, renal morphological changes and molecular changes via real-time polymerase chain reaction and immunoblotting. Furthermore, high glucose (HG)- or palmitate (PA)-stimulated mouse mesangial cells or mouse podocytes were treated with DHZ for 24 h. As a result, DHZ markedly reduced renal glycerol accumulation and albuminuria excretion through improvement of thickened glomerular basement membrane, podocyte loss and slit diaphragm reduction. In the renal cortex in the HFD group, phospho-AMPK and nephrin expression reduced, whereas arginase 2 and CD68 expression increased; however, these changes were recovered after DHZ administration. Increased reactive oxygen species (ROS) stimulated by HG or PA in podocytes was inhibited by DHZ treatment. Collectively, these findings indicate that DHZ ameliorates DN via inhibits of lipotoxicity-induced inflammation and ROS formation.

Original languageEnglish
Pages (from-to)8725-8733
Number of pages9
JournalJournal of Cellular and Molecular Medicine
Volume25
Issue number18
DOIs
Publication statusPublished - 2021 Sep

Keywords

  • dehydrozingerone
  • diabetic nephropathy
  • inflammation
  • lipotoxicity
  • reactive oxygen species

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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