Lowering the dietary omega-6: omega-3 does not hinder nonalcoholic fatty-liver disease development in a murine model.
It is hypothesized that a high dietary n-6:n-3 (eg, 10-20:1) is partly responsible for the rise in obesity and related health ailments. However, no tightly controlled studies using high-fat diets differing in the n-6:n-3 have tested this hypothesis. The aim of the study was to determine the role that the dietary n-6:n-3 plays in non-alcoholic fatty-liver disease (NAFLD) and colitis development. We hypothesized that reducing the dietary n-6:n-3 would hinder the development of NAFLD and colitis. Male C57BL/6 J mice were fed high-fat diets, differing in the n-6:n-3 (1:1, 5:1, 10:1, 20:1), for 20 weeks. Gas chromatography-mass spectrometry was used to analyze the hepatic phospholipid arachidonic acid (AA):eicosapentaenoic acid and AA:docosahexaenoic acid. Hepatic metabolism, inflammatory signaling, macrophage polarization, gene expression of inflammatory mediators, oxidative and endoplasmic reticulum stress, and oxidative capacity were assessed as well as colonic inflammatory signaling, and gene expression of inflammatory mediators and tight-junction proteins. Although reducing the dietary n-6:n-3 lowered the hepatic phospholipid AA:eicosapentaenoic acid and AA:docosahexaenoic acid in a dose-dependent manner and mildly influenced inflammatory signaling, it did not significantly attenuate NAFLD development. Furthermore, the onset of NAFLD was not paired to colitis development or changes in tight-junction protein gene expression. In conclusion, reducing the dietary n-6:n-3 did not attenuate NAFLD progression; nor is it likely that colitis, or gut permeability, plays a role in NAFLD initiation in this model.
Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, SC, 29209, USA.
Reilly T
RT
Enos
Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, SC, 29209, USA.
Kandy T
KT
Velázquez
Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, SC, 29209, USA.
Jamie L
JL
McClellan
Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, SC, 29209, USA.
Taryn L
TL
Cranford
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA.
Michael D
MD
Walla
Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, SC, 29209, USA. Electronic address: Angela.Murphy@uscmed.sc.edu.
E Angela
EA
Murphy
D000818:Animals; D016718:Arachidonic Acid / Q000032:analysis / Q000378:metabolism; D003092:Colitis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018752:Diet, Fat-Restricted; D066273:Diet, Western / Q000009:adverse effects; D004195:Disease Models, Animal; D018450:Disease Progression; D059865:Endoplasmic Reticulum Stress; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000009:adverse effects* / Q000032:analysis / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage / Q000009:adverse effects*; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D018384:Oxidative Stress; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D011897:Random Allocation; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D018836:Inflammation Mediators; D010743:Phospholipids; D062725:Tight Junction Proteins; D016718:Arachidonic Acid
Colitis; High-fat diet; Murine model; Nonalcoholic fatty-liver disease; Omega-6:omega-3; α-Linolenic acid