Reversal of hepatic steatosis by omega-3 fatty acids measured non-invasively by (1) H-magnetic resonance spectroscopy in a rat model

Living donors with marked (> 33%) macrovesicular steatosis (MaS) are excluded from living donor liver transplantation procedures. Experimental studies have shown that the development of steatosis can be prevented by supplementation with omega-3 fatty acids (FA), but no studies have investigated the reduction of steatosis using omega-3 FA. The aim of the present study was to investigate whether administration of omega-3 FA is effective in reducing steatosis. After fatty liver (FL) induction by a 3-week methionine/choline-deficient (MCD) diet, male Wistar rats were daily administered per gavage omega-3 FA (FL+Omega-3), omega-3-poor lipid solution (FL+Lipid), or NaCl (FL+NaCl) during 2 weeks. Control animals received standard chow without treatment. Determination of steatosis degree was performed before, during, and after treatment by clinical 3.0 T ¹H-magnetic resonance spectroscopy (¹H-MRS) and by histology and gas chromatography at the end of the 2-week treatment period. Hepatic fat content (¹H-MRS) was significantly reduced after 1 and 2 weeks of omega-3 FA treatment. Histological analysis revealed a mild (5-33%) MaS degree in omega-3-treated animals vs severe (> 66%) MaS in the FL+Lipid and FL+NaCl groups. Hepatic omega-6 : 3 FA ratio and total FA content were reduced in the FL+Omega-3 group. Furthermore, de novo lipogenesis (C16, C16 : 1ω7, C18 : 1ω9) was also lowered. The reduction in hepatic fat content was associated with decreased lobular inflammation and hepatic tumor necrosis factor- α and interleukin levels as well as an increased antioxidative capacity. Omega-3 FA are capable of reversing severe hepatic MaS and ameliorating pathophysiological features of non-alcoholic steatohepatitis such as hepatocellular damage, lobular inflammation, and a reduced antioxidative capacity.