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

Yamuna Sucedaram; Edward James Johns; Ruby Husain; Munavvar Abdul Sattar; Mohammed H Abdulla; Giribabu Nelli; Nur Syahrina Rahim; Manizheh Khalilpourfarshbafi; Nor Azizan Abdullah

doi:10.2147/JIR.S299083

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

J Inflamm Res. 2021 Mar 5:14:689-710. doi: 10.2147/JIR.S299083. eCollection 2021.

Authors

Yamuna Sucedaram¹, Edward James Johns², Ruby Husain³, Munavvar Abdul Sattar⁴, Mohammed H Abdulla², Giribabu Nelli³, Nur Syahrina Rahim⁵, Manizheh Khalilpourfarshbafi¹, Nor Azizan Abdullah¹

Affiliations

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

Abstract

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: hepatic steatosis; macrophage infiltration; mesangial expansion; obesity; ovariectomy.

Grants and funding

The authors fully acknowledge the Fundamental Research Grant Scheme (FRGS) grant (FP006-2017A), University Malaya Research Fund Special Assistance (BKS) grant (BKS072-2017) and Postgraduate Research Fund (PPP) grant (PG122-2016A) provided by the Universiti Malaya, Malaysia.