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


CONCLUSIONS
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.
Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Hendrik A
HA
Marsman
Michal
M
Heger
Jaap J
JJ
Kloek
Syert L
SL
Nienhuis
Jochem R
JR
van Werven
Aart J
AJ
Nederveen
Fiebo Jw
FJ
Ten Kate
Jaap
J
Stoker
Thomas M
TM
van Gulik
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002796:Choline Deficiency / Q000150:complications; D002849:Chromatography, Gas; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008715:Methionine / Q000172:deficiency; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D008715:Methionine