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

J Gastroenterol Hepatol. 2011 Feb;26(2):356-63. doi: 10.1111/j.1440-1746.2010.06326.x.

Abstract

Background and aim: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Choline Deficiency / complications
  • Chromatography, Gas
  • Dietary Supplements*
  • Disease Models, Animal
  • Fatty Acids, Omega-3 / pharmacology*
  • Fatty Liver / drug therapy*
  • Fatty Liver / etiology
  • Fatty Liver / metabolism
  • Inflammation Mediators / metabolism
  • Interleukin-6 / metabolism
  • Lipid Metabolism / drug effects*
  • Liver / drug effects*
  • Liver / metabolism
  • Magnetic Resonance Spectroscopy*
  • Male
  • Methionine / deficiency
  • Rats
  • Rats, Wistar
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • Fatty Acids, Omega-3
  • Inflammation Mediators
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Methionine