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

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...

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Autores principales:	Martine C. Morrison, Gopala K. Yakala, Wen Liang, Peter Y. Wielinga, Kanita Salic, Arianne van Koppen, Tushar Tomar, Robert Kleemann, Peter Heeringa, Teake Kooistra
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5d0b11c397ed444ea48d9a196dac1f2f
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spelling	oai:doaj.org-article:5d0b11c397ed444ea48d9a196dac1f2f2021-12-02T15:06:16ZProtective effect of rosiglitazone on kidney function in high-fat challenged human-CRP transgenic mice: a possible role for adiponectin and miR-21?10.1038/s41598-017-02444-22045-2322https://doaj.org/article/5d0b11c397ed444ea48d9a196dac1f2f2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02444-2https://doaj.org/toc/2045-2322Abstract 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.Martine C. MorrisonGopala K. YakalaWen LiangPeter Y. WielingaKanita SalicArianne van KoppenTushar TomarRobert KleemannPeter HeeringaTeake KooistraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Martine C. Morrison Gopala K. Yakala Wen Liang Peter Y. Wielinga Kanita Salic Arianne van Koppen Tushar Tomar Robert Kleemann Peter Heeringa Teake Kooistra Protective effect of rosiglitazone on kidney function in high-fat challenged human-CRP transgenic mice: a possible role for adiponectin and miR-21?
description	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.
format	article
author	Martine C. Morrison Gopala K. Yakala Wen Liang Peter Y. Wielinga Kanita Salic Arianne van Koppen Tushar Tomar Robert Kleemann Peter Heeringa Teake Kooistra
author_facet	Martine C. Morrison Gopala K. Yakala Wen Liang Peter Y. Wielinga Kanita Salic Arianne van Koppen Tushar Tomar Robert Kleemann Peter Heeringa Teake Kooistra
author_sort	Martine C. Morrison
title	Protective effect of rosiglitazone on kidney function in high-fat challenged human-CRP transgenic mice: a possible role for adiponectin and miR-21?
title_short	Protective effect of rosiglitazone on kidney function in high-fat challenged human-CRP transgenic mice: a possible role for adiponectin and miR-21?
title_full	Protective effect of rosiglitazone on kidney function in high-fat challenged human-CRP transgenic mice: a possible role for adiponectin and miR-21?
title_fullStr	Protective effect of rosiglitazone on kidney function in high-fat challenged human-CRP transgenic mice: a possible role for adiponectin and miR-21?
title_full_unstemmed	Protective effect of rosiglitazone on kidney function in high-fat challenged human-CRP transgenic mice: a possible role for adiponectin and miR-21?
title_sort	protective effect of rosiglitazone on kidney function in high-fat challenged human-crp transgenic mice: a possible role for adiponectin and mir-21?
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5d0b11c397ed444ea48d9a196dac1f2f
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Protective effect of rosiglitazone on kidney function in high-fat challenged human-CRP transgenic mice: a possible role for adiponectin and miR-21?

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