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01 March 2019 : Animal Research  

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

Ying Li12ABCDEFG, Tian Xia2A*, Rong Li2A, Gary Tse34EF, Tong Liu1EF, Guangping Li1A

DOI: 10.12659/MSM.913461

Med Sci Monit 2019; 25:1582-1589

Abstract

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.

Keywords: Nephrology, Obesity, Podocytes, PPAR gamma, Thiazolidinediones, Adiponectin, Blood Glucose, Glomerulonephritis, Membranous, Hypoglycemic Agents, Kidney, Mice, Inbred C57BL, Pioglitazone, Serum Albumin

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750