A novel rat model of fatty organ degeneration induced by poloxamer 407

Abstract

Abstract. Traditional methods of inducing hyperlipidemia in animal models are either costly (genetic manipulation) or it is difficult to control for the effects of other variables. For example, during high-fat feeding, the amount of high-fat diet intake per animal cannot be precisely controlled. The aim of this study was to develop an experimental model of fatty organ degeneration induced by poloxamer 407 (P-407). The study was conducted in 2-month-old, male Sprague-Dawley rats that were administered intraperitoneally with either 10% (w/w) P-407 (1 g/kg) or saline (10 mL/kg) for 4 months. Their lipid profile, organ degeneration due to fat deposition, and body mass were assessed. Intraperitoneal administration of P-407 resulted in significant increases in plasma triglycerides (P ≤ 0.001), total cholesterol (P < 0.001), high-density lipoprotein-cholesterol (P ≤ 0.001), and low-density lipoprotein (P < 0.001) cholesterol. In contrast to the control group, fatty tissue degeneration was observed in the liver, spleen, and kidneys of P-407-treated rats. Positive correlations between fatty tissue degeneration, and the atherogenic index of plasma (P < 0.001) and the ratio of total cholesterol to high-density-lipoprotein (P < 0.001) were identified. In addition, treatment with P-407 for 3 to 4 months caused a significant reduction in body mass relative to controls (P < 0.001). Thus, this study describes the development of a cost-effective experimental rat model of organ degeneration, characterized by fat accumulation in the liver, spleen, and kidneys, which could be used for the study of steatosis and related diseases arising from sustained untreated dyslipidemia. Furthermore, both the atherogenic index of plasma and the ratio of total cholesterol to high-density lipoprotein-cholesterol can be used to predict the risk of fatty tissue degeneration in this model. The study was approval of the University of Jishou Biomedical Research Ethics Committee, China.