Dietary Omega-3 and Omega-6 Polyunsaturated Fatty Acids Modulate Hepatic Pathology

Authors

Saraswoti Khadge, University of Nebraska Medical Center
J. Graham Sharp, University of Nebraska Medical CenterFollow
Geoffrey M. Thiele, University of Nebraska Medical CenterFollow
Timothy R. McGuireFollow
Lynell W. Klassen, University of Nebraska Medical CenterFollow
Michael J. Duryee, University of Nebraska Medical CenterFollow
Holly C. Britton, University of Nebraska Medical CenterFollow
Jordan Beck, University of Nebraska-Lincoln
Paul N. Black, University of Nebraska-LincolnFollow
Concetta DiRusso, University of Nebraska - LincolnFollow
James Talmadge, University of Nebraska Medical CenterFollow

Date of this Version

2018

Citation

Published in final edited form as: J Nutr Biochem. 2018 February ; 52: 92–102. doi:10.1016/j.jnutbio.2017.09.017.

Comments

HHS Public Access Author manuscript J Nutr Biochem. Author manuscript; available in PMC 2019 February 01.

Abstract

Recent evidence has suggested that dietary polyunsaturated fatty acids (PUFAs) modulate inflammation; however, few studies have focused on the pathobiology of PUFA using isocaloric and isolipidic diets and it is unclear if the associated pathologies are due to dietary PUFA composition, lipid metabolism or obesity, as most studies compare diets fed ad libitum. Our studies used isocaloric and isolipidic liquid diets (35% of calories from fat), with differing compositions of omega (ω)-6 or long chain (Lc) ω-3 PUFA that were pair-fed and assessed hepatic pathology, inflammation and lipid metabolism. Consistent with an isocaloric, pair-fed model we observed no significant difference in diet consumption between the groups. In contrast, the body and liver weight, total lipid level and abdominal fat deposits were significantly higher in mice fed an ω-6 diet. An analysis of the fatty acid profile in plasma and liver showed that mice on the ω-6 diet had significantly more arachidonic acid (AA) in the plasma and liver, whereas, in these mice ω-3 fatty acids such as eicosapentaenoic acid (EPA) were not detected and docosahexaenoic acid (DHA) was significantly lower. Histopathologic analyses documented that mice on the ω-6 diet had a significant increase in macrovesicular steatosis, extramedullary myelopoiesis (EMM), apoptotic hepatocytes and decreased glycogen storage in lobular hepatocytes, and hepatocyte proliferation relative to mice fed the Lc ω-3 diet. Together, these results support PUFA dietary regulation of hepatic pathology and inflammation with implications for enteral feeding regulation of steatosis and other hepatic lesions.