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Med Sci Monit. 2019 Mar 1;25:1582-1589. doi: 10.12659/MSM.913461.

Renal-Protective Effects of the Peroxisome Proliferator-Activated Receptor-γ Agonist Pioglitazone in ob/ob Mice.

Li Y1,2, Xia T2, Li R2, Tse G3,4, Liu T1, Li G1.

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Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China (mainland).
Department of Nephrology, Second Hospital of Tianjin Medical University, Tianjin, China (mainland).
Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, Hong Kong.
Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China (mainland).


BACKGROUND This study investigated the therapeutic effects of the peroxisome proliferator-activated receptor-γ (PPARγ) agonist pioglitazone in ob/ob mice with obesity-related glomerulopathy (ORG). MATERIAL AND METHODS A total of 24 mice were divided into 3 groups: wild-type C57BL/6 mice (n=8), ob/ob mice (n=8), and ob/ob mice receiving pioglitazone treatment (n=8). Body mass, blood glucose, serum adiponectin (ADP), and urine microalbumin (mALB) levels were determined. Renal histology was examined using light and electron microscopy. Wilms tumor 1 (WT1), Zonula occludens-1 (ZO-1), AMP activated protein kinase (AMPK), and NADPH oxidase-4 (NOX-4) expression were evaluated by immunohistochemistry and Western blot. RESULTS Serum ADP did not alter between weeks 0 and 12 in the control group, while the ob/ob mice showed a time-dependent decrease that was prevented by pioglitazone. Urinary mALB did not alter between week 0 and 12 in the control group, but was higher in week 0 and week 12 in the ob/ob group. Pioglitazone prevented the rise in urinary mALB in week 12. Histology revealed glomerulomegaly, mesangial proliferation, focal segmental glomerulosclerosis, and foot processes fusion in the ob/ob group, which were ameliorated by pioglitazone treatment. Compared to the control group, ob/ob mice had a higher kidney index and glomerular diameter, which were reduced by pioglitazone treatment. Immunohistochemical and Western blot experiments revealed lower expression levels of WT1, ZO-1, and AMPK and higher NOX-4 expression level in the ob/ob group, which was prevented by pioglitazone treatment. CONCLUSIONS Pioglitazone, a PPARγ agonist, can prevent ORG, probably by reducing oxidative stress.


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