Uninephrectomy augments the effects of high fat diet induced obesity on gene expression in mouse kidney

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1842

Article

Gai, Zhibo¹  Hiller, Christian¹  Chin, Siew Hung^2,3,4  Hofstetter, Lia¹  Stieger, Bruno¹  Konrad, Daniel^2,3,4  Kullak-Ublick, Gerd A.¹ 

[1] Univ Zurich Hosp, Dept Clin Pharmacol & Toxicol, Zurich, Switzerland

[2] Univ Childrens Hosp, Div Pediat Endocrinol & Diabetol, Zurich, Switzerland

[3] Univ Childrens Hosp, Childrens Res Ctr, Zurich, Switzerland

[4] Univ Zurich, Zurich Ctr Integrat Human Physiol, CH-8006 Zurich, Switzerland

关键词: Gene regulation;    Nuclear receptor;    Bile acids;    Organic anion transporter;    Wnt signaling, BMP pathway;   

DOI  :  10.1016/j.bbadis.2014.07.001

来源: Elsevier

【 摘 要 】

Obesity has been reported as an independent risk factor for chronic kidney disease, leading to glomerulosclerosis and renal insufficiency. To assess the relationship between a reduced nephron number and a particular susceptibility to obesity-induced renal damage, mice underwent uninephrectomy (UNX) followed by either normal chow or high-fat diet (HFD) and were compared with sham-operated control mice. After 20 weeks of dietary intervention, HFD-fed control mice presented characteristic features of progressive nephropathy, including albuminuria, glomerulosclerosis, renal fibrosis and oxidative stress. These changes were more pronounced in HFD-fed mice that had undergone uninephrectomy. Analysis of gene expression in mouse kidney by whole genome microarrays indicated that high fat diet led to more changes in gene expression than uninephrectomy. HFD affected mainly genes involved in lipid metabolism and transport, whereas the combination of UNX and HFD additionally altered the expression of genes belonging to cytoskeleton remodeling, fibrosis and hypoxia pathways. Canonical pathway analyses identified the farnesoid X receptor (FXR) as a potential key mediator for the observed changes in gene expression associated with UNX-HFD. In conclusion, HFD-induced kidney damage is more pronounced following uninephrectomy and is associated with changes in gene expression that implicate FXR as a central regulatory pathway. (C) 2014 The Authors. Published by Elsevier B.V.

【 授权许可】

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