Increased renal cellular senescence in murine high-fat diet: effect of the senolytic drug quercetin

Seo Rin Kim, Kai Jiang, Mikolaj Ogrodnik, Xiaojun Chen, Xiang Yang Zhu, Hannah Lohmeier, L. Ahmed, Hui Tang, Tamara Tchkonia, LaTonya Hickson, James L Kirkland, Lilach O Lerman

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Obesity and dyslipidemia can be associated with cellular senescence, and may impair kidney function. However, whether senescence contributes to renal dysfunction in these conditions remains unclear. Quercetin is an abundant dietary flavonoid that selectively clears inhibiting PI3K/AKT and p53/p21/serpines and inducing apoptosis. We hypothesized that high-fat-diet-induced obesity causes renal senescence, which would be mitigated by quercetin. C57BL/6J mice fed either standard chow or high-fat diets (HFDs) were treated with quercetin (50 mg/kg) or vehicle 5-days biweekly via oral gavage for 10 weeks. Subsequently, renal function was studied in vivo using magnetic resonance imaging, and renal senescence and histology were evaluated ex vivo. Mice fed with a HFD developed obesity and hypercholesterolemia, whereas renal size remained unchanged. Murine obesity impaired renal function and cortical oxygenation, and induced glomerulomegaly. Renal markers of senescence (eg, expression of p16, p19, and p53) and its secretory phenotype were upregulated in the obese hypercholesterolemic compared to lean mice in renal tubular cells, but attenuated in quercetin-treated murine kidneys, as was renal fibrosis. Quercetin treatment also increased renal cortical oxygenation and decreased plasma creatinine levels in obese mice, whereas body weight and cholesterol levels were unaltered. Therefore, murine obesity and dyslipidemia induce renal tissue senescence and impairs kidney function, which is alleviated by chronic senolytic treatment. These findings implicate senescence in loss of kidney function in murine dyslipidemia and obesity, and support further studies of senolytic therapy in obesity.

Original languageEnglish (US)
JournalTranslational Research
DOIs
StateAccepted/In press - Jan 1 2019

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Cell Aging
Quercetin
High Fat Diet
Nutrition
Fats
Kidney
Pharmaceutical Preparations
Oxygenation
Obesity
Histology
Magnetic resonance
Dyslipidemias
Phosphatidylinositol 3-Kinases
Flavonoids
Creatinine
Cholesterol
Tissue
Apoptosis
Plasmas
Imaging techniques

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Biochemistry, medical
  • Physiology (medical)

Cite this

Increased renal cellular senescence in murine high-fat diet : effect of the senolytic drug quercetin. / Kim, Seo Rin; Jiang, Kai; Ogrodnik, Mikolaj; Chen, Xiaojun; Zhu, Xiang Yang; Lohmeier, Hannah; Ahmed, L.; Tang, Hui; Tchkonia, Tamara; Hickson, LaTonya; Kirkland, James L; Lerman, Lilach O.

In: Translational Research, 01.01.2019.

Research output: Contribution to journalArticle

Kim, Seo Rin ; Jiang, Kai ; Ogrodnik, Mikolaj ; Chen, Xiaojun ; Zhu, Xiang Yang ; Lohmeier, Hannah ; Ahmed, L. ; Tang, Hui ; Tchkonia, Tamara ; Hickson, LaTonya ; Kirkland, James L ; Lerman, Lilach O. / Increased renal cellular senescence in murine high-fat diet : effect of the senolytic drug quercetin. In: Translational Research. 2019.
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AU - Zhu, Xiang Yang

AU - Lohmeier, Hannah

AU - Ahmed, L.

AU - Tang, Hui

AU - Tchkonia, Tamara

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