Conversion of Omega-6 to Omega-3 Fatty Acids Protects Against Liver Injury in a Murine Model.

INTRODUCTION

Parenteral nutrition (PN) is life-saving for patients with intestinal malabsorption. Soybean oil lipid emulsions (SOLEs) administered as part of PN can cause liver injury that progresses to death or need for transplantation, partly due to high level of proinflammatory omega-6 (n6) polyunsaturated fatty acids. Fat-1 mice express an omega-3 (n3) fatty acid desaturase enzyme that converts n6 to n3 polyunsaturated fatty acids that have anti-inflammatory/anti-steatotic properties.

MATERIALS AND

METHODS

We hypothesized that fat-1 mice will have less severe fatty liver disease compared to C57Bl/6J mice when administered identical lipid doses (4 g/kg/d) of either SOLE or mixed-oil emulsion in a 19-d model of PN-induced hepatosteatosis. Chow-fed, age-matched mice served as controls. The primary outcome was hepatosteatosis severity assessed by histology and triglyceride assay.

RESULTS

Compared to C57Bl/6J mice, fat-1 mice had reduced histologic hepatosteatosis and lower liver triglyceride levels for PN + saline (P = 0.005) and PN + SOLE (P = 0.02) groups. C57Bl/6J mice had higher n6:n3 ratios than fat-1 mice for chow (P < 0.001), PN + saline (P = 0.01), PN + mixed-oil emulsion (P = 0.001), and PN + SOLE (P < 0.001) groups. Fat-1 mice developed less severe fatty liver disease compared to C57Bl/6J mice in a PN steatosis model.

CONCLUSIONS

In a murine model of PN-induced hepatosteatosis, fat-1 mice expressing an n3 fatty acid desaturase enzyme developed less severe fatty liver disease compared to C57Bl/6J mice administered identical doses of ILEs.