Hepatic regeneration and functional recovery following partial liver resection in an experimental model of hepatic steatosis treated with omega-3 fatty acids

Abstract

Omega-3 fatty acids (FAs) have been shown to reduce experimental hepatic steatosis and protect the liver from ischaemia-reperfusion injury. The aim of this study was to examine the effects of omega-3 FAs on regeneration of steatotic liver. Steatosis was induced in rats by a 3-week methionine/choline-deficient diet, which was continued for an additional 2 weeks in conjunction with oral administration of omega-3 FAs or saline solution. Steatosis was graded histologically and quantified by proton magnetic resonance spectroscopy ((1) H-MRS) before and after the diet/treatment. Liver function was determined by (99m) Tc-labelled mebrofenin hepatobiliary scintigraphy (HBS). In separate experiments, the hepatic regenerative capacity and functional recovery of omega-3 FA-treated, saline-treated or non-steatotic (control) rats were investigated 1, 2, 3 and 5 days after partial (70 per cent) liver resection by measurement of liver weight change and hepatocyte proliferation (Ki-67) and HBS. Severe steatosis (over 66 per cent) in the saline group was reduced by omega-3 FAs to mild steatosis (less than 33 per cent), and hepatic fat content as assessed by (1) H-MRS decreased 2·2-fold. (99m) Tc-mebrofenin uptake in the saline group was more than 50 per cent lower than in the control group, confirming the functional effects of steatosis. (99m) Tc-mebrofenin uptake and regenerated liver mass were significantly greater in the omega-3 group compared with the saline group on days 1 and 3. The posthepatectomy proliferation peak response was delayed until day 2 in saline-treated rats, compared with day 1 in the omega-3 and control groups. Omega-3 FAs effectively reduced severe hepatic steatosis, which was associated with improved liver regeneration and functional recovery following partial hepatectomy.