Protective effect of rosiglitazone on kidney function in high-fat challenged human-CRP transgenic mice: A possible role for adiponectin and miR-21?

Martine C. Morrison*, Gopala K. Yakala, Wen Liang, Peter Y. Wielinga, Kanita Salic, Arianne van Koppen, Tushar Tomar, Robert Kleemann, Peter Heeringa, Teake Kooistra

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Obesity-related albuminuria is associated with decline of kidney function and is considered a first sign of diabetic nephropathy. Suggested factors linking obesity to kidney dysfunction include low-grade inflammation, insulin resistance and adipokine dysregulation. Here, we investigated the effects of two pharmacological compounds with established anti-inflammatory properties, rosiglitazone and rosuvastatin, on kidney dysfunction during high-fat diet (HFD)-induced obesity. For this, human CRP transgenic mice were fed standard chow, a lard-based HFD, HFD+ rosuvastatin or HFD+ rosiglitazone for 42 weeks to study effects on insulin resistance; plasma inflammatory markers and adipokines; and renal pathology. Rosiglitazone but not rosuvastatin prevented HFD-induced albuminuria and renal fibrosis and inflammation. Also, rosiglitazone prevented HFD-induced KIM-1 expression, while levels were doubled with rosuvastatin. This was mirrored by miR-21 expression, which plays a role in fibrosis and is associated with renal dysfunction. Plasma insulin did not correlate with albuminuria. Only rosiglitazone increased circulating adiponectin concentrations. In all, HFD-induced albuminuria, and renal inflammation, injury and fibrosis is prevented by rosiglitazone but not by rosuvastatin. These beneficial effects of rosiglitazone are linked to lowered miR-21 expression but not connected with the selectively enhanced plasma adiponectin levels observed in rosiglitazone-treated animals.

Original languageEnglish
Article number2915
Number of pages10
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - Jun-2017

Keywords

  • PROXIMAL TUBULAR CELLS
  • C-REACTIVE PROTEIN
  • DIABETES-MELLITUS
  • ALBUMINURIA
  • OBESITY
  • DISEASE
  • INFLAMMATION
  • DYSFUNCTION
  • RECEPTOR
  • INSULIN

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