The Effects of Fenretinide in the ApoE -/- Mouse Model of Atherosclerosis

Abstract

Abstract: Background and Purpose Fenretinide is a synthetic retinoid that has shown positive results in preventing adiposity, enhancing insulin resistance, blocking lipid formation in mice fed a high fat diet. This project aimed to explore the effects of Fenretinide in the liver of the female ApoE-/- mice model of atherosclerosis. Experimental Approach The ApoE-/- mouse model of atherosclerosis, an established model for atherosclerosis and NAFLD, was used. Western blotting, RT-qPCR, and hepatic triglyceride assay techniques were used on samples from the liver and the serum of female ApoE-/- mice. Key Results Fenretinide prevented weight gain in the female ApoE-/- mice via lean mass, but did not prevent adiposity. Fenretinide normalized the expression of proinflammatory genes, TNF-α, MCP-1 (P < 0.05), trended down the expression of the other proinflammatory genes (IL-1β, CD68), and trended up the expression the anti-inflammatory gene (IL-10) when compared to the group on high fat diet. Fenretinide decreased the expression of FGF21 (P < 0.05). Fenretinide decreased the expression of total mTOR and total IRE1α (P < 0.05) Fenretinide trended up the phosphorylation of AMPKα when compared to the group on high fat diet. Fenretinide trended down the expression of Collagen 1(COL1A1) and MMP9 in the liver and decreased the expression of TIMP2 (P < 0.05) when compared to the group on high fat diet. . Conclusions and Implications The results of this project demonstrated that Fenretinide has favorable effects on the inflammatory response in the liver which is due to the high fat diet. Further investigations in other relevant tissues in this model might shed further understanding for the pathogenesis and a potential new approach for prevention and the treatment of NAFLD and Atherosclerosis.