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Exposure to High-Fat Style Diet Induced Renal and Liver Structural Changes, Lipid Accumulation and Inflammation in Intact and Ovariectomized Female Rats

Authors Sucedaram Y, Johns EJ, Husain R, Abdul Sattar M, H Abdulla M, Nelli G, Rahim NS, Khalilpourfarshbafi M, Abdullah NA

Received 25 December 2020

Accepted for publication 18 February 2021

Published 5 March 2021 Volume 2021:14 Pages 689—710

DOI https://doi.org/10.2147/JIR.S299083

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Ning Quan


Yamuna Sucedaram,1 Edward James Johns,2 Ruby Husain,3 Munavvar Abdul Sattar4 , Mohammed H Abdulla,2 Giribabu Nelli,3 Nur Syahrina Rahim,5 Manizheh Khalilpourfarshbafi,1 Nor Azizan Abdullah1

1Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia; 2Department of Physiology, University College Cork, Cork, T12 K8AF, Ireland; 3Department of Physiology, Universiti Malaya, Kuala Lumpur, 50603, Malaysia; 4School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, 11800, Pulau Pinang, Malaysia; 5Faculty of Medicine & Health Science, Universiti Sains Islam Malaysia, Nilai, 71800, Malaysia

†Prof. Dr. Munavvar Abdul Sattar passed away on January 6, 2021

Correspondence: Nor Azizan Abdullah
Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia
Tel +60122386655
Fax +60379674791
Email [email protected]

Purpose: We hypothesized that low estrogen levels aggravate obesity-related complications. Diet-induced obesity can cause distinct pathologies, including impaired glucose tolerance, inflammation, and organ injury that leads to fatty liver and chronic kidney diseases. To test this hypothesis, ovariectomized (OVX) rats were fed a high-fat style diet (HFSD), and we examined structural changes and inflammatory response in the kidney and liver.
Methods: Sprague-Dawley female rats were ovariectomized or sham-operated and divided into four groups: sham-operated rats fed a normal diet (ND); ovariectomized rats fed a normal diet (OVX-ND); sham-operated rats fed a HFSD; ovariectomized rats fed a high-fat style diet (OVX-HFSD). Mean blood pressure and fasting blood glucose were measured on weeks 0 and 10. The rats were sacrificed 10 weeks after initiation of ND or HFSD, the kidney and liver were harvested for histological, immunohistochemical and immunofluorescence studies.
Results: HFSD-fed rats presented a significantly greater adiposity index compared to their ND counterparts. Liver index, fasting blood glucose and mean blood pressure was increased in OVX-HFSD rats compared to HFSD rats at study terminal. Histological and morphometric studies showed focal interstitial mononuclear cell infiltration in the kidney of HFSD rats with mesangial expansion being greater in the OVX-HFSD rats. Both HFSD fed groups showed increased expressions of renal inflammatory markers, namely TNF-alpha, IL-6 and MCP-1, and infiltrating M1 macrophages with some influence of ovarian hormonal status. HFSD-feeding also caused hepatocellular steatosis which was aggravated in ovariectomized rats fed the same diet. Furthermore, hepatocellular ballooning was observed only in the OVX-HFSD rats. Similarly, HFSD-fed rats showed increased expressions of the inflammatory markers and M1 macrophage infiltration in the liver; however, only IL-6 expression was magnified in the OVX-HFSD.
Conclusion: Our data suggest that some of the structural changes and inflammatory response in the kidney and liver of rats fed a HFSD are exacerbated by ovariectomy.

Keywords: obesity, ovariectomy, macrophage infiltration, mesangial expansion, hepatic steatosis

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