Abstract: SA-PO505
Deletion of Peroxisome-Proliferator-Activated Receptor δ in Mice Promotes High-Fat-Diet-Induced Renal Injury
Session Information
- Diabetic Kidney Disease: Basic - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- You, Yongke, The Chinese University of HongKong, Hong Kong, China
- Chen, Hai-Yong, The University of Hong Kong, Hong Kong, China
- Huang, Yu, The Chinese University of Hong Kong, Shatin, China
- Lan, Hui Y., The Chinese University of HongKong, Hong Kong, China
Background
Peroxisome proliferator-activated receptor δ (PPARδ), the least studied member of the PPAR group in the nuclear receptor superfamily, plays a crucial role in cellular metabolic functions and other physiological processes. Recent evidence highlights the therapeutic potential of PPARδ agonists in obesity, dyslipidaemia, insulin resistance/type 2 diabetes. However, little is known the role of PPARδ in the pathogenesis of obesity related renal injury. It is reported that PPARδ gene is a primary target of 1a,25-dihydroxyvitamin D3 (calcitriol), the aim of this study is to investigate the effects of calcitriol on the role of PPARδ in HFD-induced renal injury.
Methods
Diet-induced obese (DIO) micewere generated on PPARδ KO, age-matched PPARδ wildtype (WT) littermates at the 6 weeks of age and were fed with high-fat-diet (HFD) for 12 weeks. In addition,12 weeks after HFD feeding, mice were treated with 1a,25-dihydroxyvitamin D3 (calcitriol) or vehicle by intraperitoneal injection at the dosage of 100 ng/kg three times a week for 4 weeks.The effects of calcitriol on the role of PPARδ in HFD-induced renal injury were evaluated by real-time quantitative polymerase-chain-reaction (qRT-PCR), western blot analysis, as well as a histological examination.
Results
Compared with control mice on a normal diet, DIO PPARδ WT mice exhibited significant renal injury, which were further exacerbated in DIO PPARδ KO mice: including 1) obviously increased expression of kidney injury molecule-1 (KIM-1),as well as histological injury revealed by Masson‘s Trichrome &PAS Staining; 2) marked up-regulation of pro-inflammatory cytokines TNF-a; 3) exacerbated renal fibrosis as demonstrated by significantly up-regulation of fibrotic matrix proteins deposition, such as a-smooth muscle actin (a-SMA) , collagen 1 and fibronectin. However, all these changes were dramatically attenuated after administration of calcitriol.
Conclusion
In conclusion, deletion of PPARδ promotes HFD-induced renal fibrosis and inflammation, and these changes could be partially attenuated by calcitriol treatment. Targeting PPARδ gene may offer a new treatment approach for obesity-related renal injury.