Chapters authored
The Role of Cholesterol in the Pathogenesis of Hypertension- Associated Nonalcoholic Steatohepatitis
Dietary cholesterol is a crucial risk factor for nonalcoholic steatohepatitis (NASH). Our recent studies indicated that high cholesterol intake was associated with the pathogenesis of hypertension-associated NASH. We developed a novel hypertensive rat model of NASH by feeding stroke-prone spontaneously hypertensive rats (SHRSP5/Dmcr) a high fat and cholesterol (HFC) diet. Histological features resembling human NASH were observed in this model. Furthermore, we investigated the kinetics of cholesterol in the rats fed an HFC diet and determined that suppression of bile acid (BA) detoxification led by HFC feeding results in cytotoxic BA accumulation in hepatocytes, which induces inflammatory response and liver damage. Sex differences in fibrogenesis were also observed in this model, and we found this was associated with a different ability in BA detoxification. Since SHRSP5/Dmcr rats are hypertensive, we investigated the role of hypertension in NASH progression by comparing NASH development among SHRSP5/Dmcr rats, spontaneously hypertensive rats and their original strain, Wistar Kyoto, with normal blood pressure. HFC diet induced more severe hepatic fibrosis in the hypertensive strains compared with the normotensive one. In conclusion, dietary cholesterol plays an essential role in the pathogenesis of NASH, and the combined action of cholesterol and hypertension further aggravates its progression.
Part of the book: Cholesterol