Exposure to high-fat style diet induced renal and liver structural changes, lipid accumulation and inflammation in intact and ovariectomized female rats

Sucedaram, Yamuna and Johns, Edward James and Husain, Ruby and Sattar, Munavvar Abdul and Abdulla, Mohammed H. and Nelli, Giribabu and Rahim, Nur Syahrina and Khalilpourfarshbafi, Manizheh and Abdullah, Nor Azizan (2021) Exposure to high-fat style diet induced renal and liver structural changes, lipid accumulation and inflammation in intact and ovariectomized female rats. Journal of Inflammation Research, 14. pp. 689-710. ISSN 1178-7031, DOI https://doi.org/10.2147/JIR.S299083.

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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.

Item Type: Article
Funders: Fundamental Research Grant Scheme (FRGS) [FP006-2017A], University Malaya Research Fund Special Assistance (BKS) grant [BKS072-2017], Postgraduate Research Fund (PPP) grant - Universiti Malaya, Malaysia [PG122-2016A]
Uncontrolled Keywords: Obesity; Ovariectomy; Macrophage infiltration; Mesangial expansion; Hepatic steatosis
Subjects: Q Science > QR Microbiology > QR180 Immunology
Divisions: Faculty of Pharmacy
Depositing User: Ms Zaharah Ramly
Date Deposited: 13 Jun 2022 02:34
Last Modified: 13 Jun 2022 02:34
URI: http://eprints.um.edu.my/id/eprint/34278

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