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
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¹ÎÇý¼÷(Min Hye-Sook) - Korea University College of Medicine Department of Internal Medicine
±èÁ¤Àº(Kim Jung-Eun) - Korea University College of Medicine Department of Internal Medicine
À̹ÌÈ(Lee Mi-Hwa) - Korea University College of Medicine Department of Internal Medicine
¼ÛÇý°æ(Song Hye-Kyoung) - Korea University College of Medicine Department of Internal Medicine
À̹ÌÁø(Lee Mi-Jin) - Korea University College of Medicine Department of Internal Medicine
ÀÌÁöÀº(Lee Ji-Eun) - Wonkwang University College of Medicine Department of Internal Medicine
±èÇö¿í(Kim Hyun-Wook) - Wonkwang University College of Medicine Department of Internal Medicine
Â÷ÁøÁÖ(Cha Jin-Joo) - Korea University College of Medicine Department of Internal Medicine
Çö¿µÀ²(Hyun Young-Youl) - Sungkyunkwan University School of Medicine Department of Internal Medicine
ÇÑÁö¿µ(Han Jee-Young) - Inha University College of Medicine Department of Pathology
Â÷´ë·æ(Cha Dae-Ryong) - Korea University College of Medicine Department of Internal Medicine
°¿µ¼±(Kang Young-Sun) - Korea University College of Medicine Department of Internal Medicine
Abstract
Background: Obesity-related metabolic disorders are closely associated with in?ammation induced by innate immunity. Toll-like receptors (TLRs) play a pivotal role in the innate immune system by activating proin?ammatorysignaling 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 ¥á [as well as interleukin (IL)-1¥â, IL-10, and interferon g]. However, the effect of TLR antagonist on kidney diseases has rarely been reported. We investigated whether the TLR antagonist GIT27 has bene?cial 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¨ù4); mice fed with a HFD (60% of total calories from fat, 5.5% from soybean oil, and 54.5% from lard, N¨ù4); and GIT27-treated mice fed with a HFD (N¨ù7).
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 in?ammatory cytokine levels. This treatment inhibited the expression of proin?ammatory cytokines in the kidneys and adipose tissue, and improved extracellular matrix expansion and tubulointerstitial ?brosis in obesity- related kidney disease.
Conclusion: 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-in?ammatory properties.
& 2014.The Korean Society of Nephrology.Published by Elsevier. All rights reserved.
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Kidney disease, Metabolic syndrome, Obesity, Toll-likereceptors
KMID :
0359920140330010033
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