title: Effects of Toll-like receptor antagonist 4,5-dihydro-3-phenyl-5-isoxasole acetic acid on the progression of kidney disease in mice on a high-fat diet.
abstract: BACKGROUND
  Obesity-related metabolic disorders are closely associated with inflammation induced by innate immunity. Toll-like receptors (TLRs) play a pivotal role in the innate immune system by activating proinflammatory signaling pathways. GIT27 (4,5-dihydro-3-phenyl-5-isoxasole acetic acid) is an active immunomodulatory agent that primarily targets macrophages and inhibits secretion of tumor necrosis factor α [as well as interleukin (IL)-1β, IL-10, and interferon γ]. However, the effect of TLR antagonist on kidney diseases has rarely been reported. We investigated whether the TLR antagonist GIT27 has beneficial effects on the progression of kidney disease in obese mice on a high-fat diet (HFD).
  
  
  METHODS
  Six-week-old male C57BL/6 mice were divided into three groups: mice fed with normal chow diet (N=4); mice fed with a HFD (60% of total calories from fat, 5.5% from soybean oil, and 54.5% from lard, N=4); and GIT27-treated mice fed with a HFD (N=7).
  
  
  RESULTS
  Glucose intolerance, oxidative stress, and lipid abnormalities in HFD mice were improved by GIT27 treatment. In addition, GIT27 treatment decreased the urinary excretion of albumin and protein in obesity-related kidney disease, urinary oxidative stress markers, and inflammatory cytokine levels. This treatment inhibited the expression of proinflammatory cytokines in the kidneys and adipose tissue, and improved extracellular matrix expansion and tubulointerstitial fibrosis in obesity-related kidney disease.
  
  
  CONCLUSIONS
  TLR inhibition by administering GIT27 improved metabolic parameters. GIT27 ameliorates abnormalities of lipid metabolism and may have renoprotective effects on obesity-related kidney disease through its anti-inflammatory properties.
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Ansan, Korea.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Min
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Ansan, Korea.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Ansan, Korea.
authors.forename: Mi Hwa
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Ansan, Korea.
authors.forename: Hye Kyoung
authors.initials: HK
authors.lastname: Song
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Ansan, Korea.
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Wonkwang University College of Medicine, Sanbon, Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Wonkwang University College of Medicine, Sanbon, Korea.
authors.forename: Hyun Wook
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Ansan, Korea.
authors.forename: Jin Joo
authors.initials: JJ
authors.lastname: Cha
authors.affiliation: Department of Internal Medicine, Sungkyunkwan University College of Medicine, Seoul, Korea.
authors.forename: Young Youl
authors.initials: YY
authors.lastname: Hyun
authors.affiliation: Department of Pathology, Inha University College of Medicine, Incheon, Korea.
authors.forename: Jee Young
authors.initials: JY
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Ansan, Korea.
authors.forename: Dae Ryong
authors.initials: DR
authors.lastname: Cha
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Ansan, Korea.
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Kang
keywords: Kidney disease; Metabolic syndrome; Obesity; Toll-like receptors