Characterizing the role of dietary fat in the development and progression of liver dysfunction.

摘要

Obesity and metabolic dysfunction are worldwide health epidemics and they have grown to unprecedented levels. Human NAFLD is directly linked to obesity and metabolic dysfunction, so attention was given to elucidating a more complete understanding of the liver's role in mediating the metabolically healthy obese phenotype and to better characterizing the potential contribution of dietary fat and fatty acids as a therapeutic supplement to obesogenic diets. Specifically, flaxseed is high in &agr;-linolenic acid (ALA; 18:3 n-3) and low in linoleic acid (LA; 18:2 n-6), and contains multiple other components such as fiber and lignans, and was investigated for its high potential to modify obesity phenotype and fatty liver disease. Additionally, we explored the temporal effect of initiating high-fat diets in various phases of adulthood. However, work in this field is complicated by an ongoing search for appropriate preclinical animal models of NAFLD as they have not been able to replicate the full spectrum of human NAFLD. As such, this dissertation sought to explore fatty liver disease in popular murine models of overnutrition, as well as a novel hen model. Major findings from this work showed that (1) exposure to a high-fat diet during early adulthood preserves metabolic homeostasis, modifies liver morphology, and protects against obesity-related disease, (2) dietary enrichment with flaxseed is capable of increasing tissue n3PUFA content, but this appeared to be only weakly related to metabolic and histological outcomes, and (3) there are limitations to the laying hen as a model of NAFLD as the pathogenic changes may not adequately match the human condition.