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

Morrison, M. C., Yakala, G. K., Liang, W., Wielinga, P. Y., Salic, K., van Koppen, A., Tomar, T., Kleemann, R., Heeringa, P. & Kooistra, T. 6-Jun-2017 In : Scientific Reports. 7, 1, 2915

Research output: Scientific - peer-reviewArticle

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

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
JournalScientific Reports
Issue number1
StatePublished - 6-Jun-2017


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