Resveratrol alleviates obesity‑associated podocyte injury in ovariectomized obese rats

Li,Bing; Xiao,Xiaoyan; Miao,Yulian; Guo,Ling; Zhen,Junhui; Li,Xianhua; Jiang,Bei; Hu,Zhao

doi:10.3892/etm.2019.8178

Resveratrol alleviates obesity‑associated podocyte injury in ovariectomized obese rats

Authors:
- Bing Li
- Xiaoyan Xiao
- Yulian Miao
- Ling Guo
- Junhui Zhen
- Xianhua Li
- Bei Jiang
- Zhao Hu
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Affiliations: Department of Nephrology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Medical Administration, Weifang Traditional Chinese Medicine Hospital, Weifang, Shandong 261041, P.R. China, Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: November 8, 2019 https://doi.org/10.3892/etm.2019.8178
Pages: 123-130
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Obesity‑associated podocyte injury increases in parallel with inflammatory responses. Resveratrol, as an anti‑inflammatory and antioxidative agent, has been proven to be effective in obesity. The purpose of the present study was to investigate the function of resveratrol in the early stages of podocyte injury in ovariectomized rats fed a high‑fat diet (HFD). The 3‑month‑old female Wistar rats were randomly divided into four groups: Sham operation with a standard diet; sham operation with a HFD; ovariectomy with a HFD (O+H); and ovariectomy plus HFD treatment with resveratrol (40 mg/kg/day) (O+H+R). Following 12 weeks, the weights of the rats were measured and serum was obtained to measure the levels of 17β‑estradiol (E2), serum lipids, serum creatinine, fasting blood glucose (FBG) and insulin. Periodic acid‑schiff staining was used to detect renal pathological changes. Meanwhile, the expression of the podocyte‑associated proteins nephrin and Wilms' tumor‑1 was investigated using immunohistochemical staining, and the levels of tumor necrosis factor‑α, interleukin‑6 and monocyte chemotactic protein‑1 in renal tissues were determined using western blotting. Compared with the O+H group, resveratrol significantly reduced the body weight, serum levels of total cholesterol, low‑density lipoprotein cholesterol, FBG and insulin resistance, and increased the levels of E2 in obese rats with an ovariectomy combined with an HFD (P<0.05). Compared with the O+H group, although the O+H+R group had no significant changes in renal pathology, the changes in the levels of podocyte‑associated proteins and inflammatory markers were significantly reversed (P<0.05). These results suggest that resveratrol may attenuate early podocyte injury by improving lipid metabolism and insulin sensitivity, and subsequently inhibiting inflammatory responses in obese rats induced by an ovariectomy with a HFD.

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1	Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, et al: National, regional, and global trends in body-mass index since 1980: Systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants. Lancet. 377:578–586. 2011. View Article : Google Scholar : PubMed/NCBI
2	Xu H: Obesity and metabolic inflammation. Drug Discov Today Dis Mech. 10:e21–e25. 2013. View Article : Google Scholar
3	Hsu CY, Iribarren C, McCulloch CE, Darbinian J and Go AS: Risk factors for end-stage renal disease: 25-year follow-up. Arch Intern Med. 169:342–350. 2009. View Article : Google Scholar : PubMed/NCBI
4	Morandi A and Maffeis C: Urogenital complications of obesity. Best Pract Res Clin Endocrinol Metab. 27:209–218. 2013. View Article : Google Scholar : PubMed/NCBI
5	Kastarinen M, Juutilainen A, Kastarinen H, Salomaa V, Karhapaa P, Tuomilehto J, Gronhagen-Riska C, Jousilahti P and Finne P: Risk factors for end-stage renal disease in a community-based population: 26-year follow-up of 25,821 men and women in eastern Finland. J Intern Med. 267:612–620. 2010. View Article : Google Scholar : PubMed/NCBI
6	Gambacciani M, Ciaponi M, Cappagli B, Benussi C, De Simone L and Genazzani AR: Climacteric modifications in body weight and fat tissue distribution. Climacteric. 2:37–44. 1999. View Article : Google Scholar : PubMed/NCBI
7	Burns KA and Korach KS: Estrogen receptors and human disease: An update. Arch Toxicol. 86:1491–1504. 2012. View Article : Google Scholar : PubMed/NCBI
8	Sayakhot P, Vincent A, Deeks A and Teede H: Potential adverse impact of ovariectomy on physical and psychological function of younger women with breast cancer. Menopause. 18:786–793. 2011. View Article : Google Scholar : PubMed/NCBI
9	Chedraui P, Escobar GS, Ramírez C, Pérez-López FR, Hidalgo L, Mannella P, Genazzani A and Simoncini T: Nitric oxide and pro-inflammatory cytokine serum levels in postmenopausal women with the metabolic syndrome. Gynecol Endocrinol. 28:787–791. 2012. View Article : Google Scholar : PubMed/NCBI
10	Mercantepe T, Unal D, Selli J, Mercantepe F, Unal B and Karabiyik TN: Protective effects of estrogen and bortezomib in kidney tissue of post-menopausal rats: An ultrastructural study. Ren Fail. 38:1129–1135. 2016. View Article : Google Scholar : PubMed/NCBI
11	Amaral LS, Silva JA, Trindade TM, Ribas WB, Macedo CL, Coimbra TM, Belo NO, Magalhaes AC and Soares TJ: Renal changes in the early stages of diet-induced obesity in ovariectomized rats. Physiol Res. 63:723–732. 2014.PubMed/NCBI
12	Meydani M and Hasan HS: Dietary polyphenols and obesity. Nutrients. 2:737–751. 2010. View Article : Google Scholar : PubMed/NCBI
13	Nagao K, Jinnouchi T, Kai S and Yanagita T: Effect of dietary resveratrol on the metabolic profile of nutrients in obese OLETF rats. Lipids Health Dis. 12:1–6. 2013. View Article : Google Scholar : PubMed/NCBI
14	Chen DQ, Hu HH, Wang YN, Feng YL, Cao G and Zhao YY: Natural products for the prevention and treatment of kidney disease. Phytomedicine. 50:50–60. 2018. View Article : Google Scholar : PubMed/NCBI
15	Chen DQ, Feng YL, Cao G and Zhao YY: Natural products as a source for antifibrosis therapy. Trends Pharmacol Sci. 39:937–952. 2018. View Article : Google Scholar : PubMed/NCBI
16	Hu HH, Chen DQ, Wang YN, Feng YL, Cao G, Vaziri ND and Zhao YY: New insights into TGF-β/Smad signaling in tissue fibrosis. Chem Biol Interact. 292:76–83. 2018. View Article : Google Scholar : PubMed/NCBI
17	Wang M, Chen DQ, Chen L, Cao G, Zhao H, Liu D, Vaziri ND, Guo Y and Zhao YY: Novel inhibitors of the cellular renin-angiotensin system components, poricoic acids, target Smad3 phosphorylation and Wnt/β-catenin pathway against renal fibrosis. Br J Pharmacol. 175:2689–2708. 2018. View Article : Google Scholar : PubMed/NCBI
18	Feng YL, Chen DQ, Vaziri ND, Guo Y and Zhao YY: Small molecule inhibitors of epithelial-mesenchymal transition for the treatment of cancer and fibrosis. Med Res Rev. 2019.(Epub ahead of print). View Article : Google Scholar
19	Chen L, Yang T, Lu DW, Zhao H, Feng YL, Chen H, Chen DQ, Vaziri ND and Zhao YY: Central role of dysregulation of TGF-β/Smad in CKD progression and potential targets of its treatment. Biomed Pharmacother. 101:670–681. 2018. View Article : Google Scholar : PubMed/NCBI
20	de la Lastra CA and Villegas I: Resveratrol as an anti-inflammatory and anti-aging agent: Mechanisms and clinical implications. Mol Nutr Food Res. 49:405–430. 2005. View Article : Google Scholar : PubMed/NCBI
21	Xia N, Daiber A, Forstermann U and Li H: Antioxidant effects of resveratrol in the cardiovascular system. Br J Pharmacol. 174:1633–1646. 2017. View Article : Google Scholar : PubMed/NCBI
22	Zhu Y, Feng B, He S, Su Z and Zheng G: Resveratrol combined with total flavones of hawthorn alleviate the endothelial cells injury after coronary bypass graft surgery. Phytomedicine. 40:20–26. 2018. View Article : Google Scholar : PubMed/NCBI
23	Huo X, Zhang T, Meng Q, Li C and You B: Resveratrol effects on a diabetic rat model with coronary heart disease. Med Sci Monit. 25:540–546. 2019. View Article : Google Scholar : PubMed/NCBI
24	Fulda S: Resveratrol and derivatives for the prevention and treatment of cancer. Drug Discov Today. 15:757–765. 2010. View Article : Google Scholar : PubMed/NCBI
25	Jeon BT, Jeong EA, Shin HJ, Lee Y, Lee DH, Kim HJ, Kang SS, Cho GJ, Choi WS and Roh GS: Resveratrol attenuates obesity-associated peripheral and central inflammation and improves memory deficit in mice fed a high-fat diet. Diabetes. 61:1444–1454. 2012. View Article : Google Scholar : PubMed/NCBI
26	Tsai CC, Tey SL, Lee MC, Liu CW, Su YT and Huang SC: Mechanism of resveratrol-induced relaxation of the guinea pig fundus. Phytomedicine. 43:55–59. 2018. View Article : Google Scholar : PubMed/NCBI
27	Kim S, Jin Y, Choi Y and Park T: Resveratrol exerts anti-obesity effects via mechanisms involving down-regulation of adipogenic and inflammatory processes in mice. Biochem Pharmacol. 81:1343–1351. 2011. View Article : Google Scholar : PubMed/NCBI
28	Tou JC: Resveratrol supplementation affects bone acquisition and osteoporosis: Pre-clinical evidence toward translational diet therapy. Biochim Biophys Acta. 1852:1186–1194. 2015. View Article : Google Scholar : PubMed/NCBI
29	Alberdi G, Rodríguez VM, Miranda J, Macarulla MT, Arias N, Andrés-Lacueva C and Portillo MP: Changes in white adipose tissue metabolism induced by resveratrol in rats. Nutr Metab (Lond). 8:292011. View Article : Google Scholar : PubMed/NCBI
30	Pan QR, Ren YL, Zhu JJ, Hu YJ, Zheng JS, Fan H, Xu Y, Wang G and Liu WX: Resveratrol increases nephrin and podocin expression and alleviates renal damage in rats fed a high-fat diet. Nutrients. 6:2619–2631. 2014. View Article : Google Scholar : PubMed/NCBI
31	Kato T and Mizuno S: Nephron, Wilms' tumor-1 (WT1), and synaptopodin expression in developingpodocytes of mice. Exp Anim. 66:183–189. 2017. View Article : Google Scholar : PubMed/NCBI
32	Zagotta I, Dimova EY, Debatin KM, Wabitsch M, Kietzmann T and Fischer-Posovszky P: Obesity and inflammation: Reduced cytokine expression due to resveratrol in a human in vitro model of inflamed adipose tissue. Front Pharmacol. 6:792015. View Article : Google Scholar : PubMed/NCBI
33	Sharma R, Sharma NK and Thungapathra M: Resveratrol regulates body weight in healthy and ovariectomized rats. Nutr Metab (Lond). 14:302017. View Article : Google Scholar : PubMed/NCBI
34	Tang J, Yan H and Zhuang S: Inflammation and oxidative stress in obesity-related glomerulopathy. Int J Nephrol. 2012:6083972012. View Article : Google Scholar : PubMed/NCBI
35	Abu-Taha M, Rius C, Hermenegildo C, Noguera I, Cerda-Nicolas JM, Issekutz AC, Jose PJ, Cortijo J, Morcillo EJ and Sanz MJ: Menopause and ovariectomy cause a low grade of systemic inflammation that may be prevented by chronic treatment with low doses of estrogen or losartan. J Immunol. 183:1393–1402. 2009. View Article : Google Scholar : PubMed/NCBI
36	Brunskill EW and Potter SS: Changes in the gene expression programs of renal mesangial cells during diabetic nephropathy. BMC Nephrol. 13:702012. View Article : Google Scholar : PubMed/NCBI
37	Batlle D, Wysocki J, Soler MJ and Ranganath K: Angiotensin-converting enzyme 2: Enhancing the degradation of angiotensin II as a potential therapy for diabetic nephropathy. Kidney Int. 81:520–528. 2012. View Article : Google Scholar : PubMed/NCBI
38	Kalani A, Mohan A, Godbole MM, Bhatia E, Gupta A, Sharma RK and Tiwari S: Wilm's tumor-1 protein levels in urinary exosomes from diabetic patients with or without proteinuria. PLoS One. 8:e601772013. View Article : Google Scholar : PubMed/NCBI
39	Matoba K, Kawanami D, Ishizawa S, Kanazawa Y, Yokota T and Utsunomiya K: Rho-kinase mediates TNF-α-induced MCP-1 expression via p38 MAPK signaling pathway in mesangial cells. Biochem Biophys Res Commun. 402:725–730. 2010. View Article : Google Scholar : PubMed/NCBI
40	Li L, Xiao N, Yang X, Gao J, Ding J, Wang T, Hu G and Xiao M: A high cholesterol diet ameliorates hippocampus-related cognitive and pathological deficits in ovariectomized mice. Behav Brain Res. 230:251–258. 2012. View Article : Google Scholar : PubMed/NCBI
41	Huang SS, Ding DF, Chen S, Dong CL, Ye XL, Yuan YG, Feng YM, You N, Xu JR, Miao H, et al: Resveratrol protects podocytes against apoptosis via stimulation of autophagy in a mouse model of diabetic nephropathy. Sci Rep. 7:456922017. View Article : Google Scholar : PubMed/NCBI