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

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.

• Authors: Ying Li, Tian Xia, Rong Li, Gary Tse, Tong Liu, Guangping Li
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 25 Pg. 1582-1589 (Mar 01 2019) ISSN: 1643-3750 [Electronic] United States
• PMID: 30820023 (Publication Type: Journal Article)

Chemical References

• Adiponectin
• Blood Glucose
• Hypoglycemic Agents
• PPAR gamma
• Serum Albumin
• Thiazolidinediones
• Pioglitazone

Topics

• Adiponectin (analysis, blood)
• Animals
• Blood Glucose
• Glomerulonephritis, Membranous (metabolism)
• Hypoglycemic Agents
• Kidney (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (metabolism)
• Oxidative Stress
• PPAR gamma (agonists, metabolism)
• Pioglitazone (metabolism, pharmacology)
• Serum Albumin (analysis)
• Thiazolidinediones