Regulation of Cholesterol Metabolism in Liver: Link to NAFLD and Impact of n-3 PUFAs

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease that affects one-third of adults in westernized countries. NAFLD represents a wide spectrum of hepatic alterations, ranging from simple triglyceride accumulation in the liver to steatohepatitis. Several pharmaceutical approaches to NAFLD management have been examined, but no particular treatment has been considered both safe and highly effective. Growing evidence reveal that supplemental fish oil, seal oil and purified n-3 fatty acids can reduce hepatic lipid content in NAFLD through extensive regulation by inhibiting lipogenesis, promoting fatty acid oxidation and suppressing inflammatory responses. Recently, the fat-1 transgenic mice capable of converting n-6 to n-3 polyunsaturated fatty acids (PUFAs) have been used to examine the effects of endogenous n-3 PUFAs on NAFLD. The increased n-3 PUFAs in fat-1 transgenic mice reduced diet-induced hyperlipidemia and fatty liver through induction of CYP7A1 expression and activation of cholesterol catabolism to bile acid. This article introduces the n-3 PUFAs, and addresses the evidence and mechanisms by which endogenously synthesized n-3 PUFAs or increased dietary n-3 PUFAs may ameliorate NAFLD.