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Title: Factors determining the progression of nonalcoholic fatty liver disease : the role of abnormal fatty acid and glucocorticoid metabolism
Author: MacFarlane, David Peter
ISNI:       0000 0004 2728 8024
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2011
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Obesity and insulin resistance are associated with a constellation of features including hypertension, dyslipidaemia, type 2 diabetes, and premature cardiovascular disease, collectively termed the metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) represents the hepatic component of this syndrome, incorporating a spectrum of liver disease with increasing morbidity and mortality, from simple steatosis, to non-alcoholic steatohepatitis (or NASH), fibrosis, cirrhosis and ultimately hepatocellular carcinoma. However, factors influencing this progression are incompletely understood. In this thesis I sought to investigate pathways which promote hepatic inflammation and fibrosis by studying two contrasting dietary models of NAFLD in mice in which the risk of hepatic inflammation, insulin resistance and fibrosis differ; namely the methionine and choline deficient diet (MCDD) which induces steatohepatitis, hepatic insulin resistance, and weight loss, and the choline deficient diet (CDD) which may be protected from insulin resistance, and leads to steatosis without inflammation or weight loss. I investigated the possible molecular mechanisms underlying these differences, and whether they influenced progression to hepatic fibrosis induced by carbon tetrachloride (CCl4).
Supervisor: Walker, Brian. ; Andrew, Ruth. Sponsor: Wellcome Trust ; British Heart Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Non-alcoholic fatty liver disease ; NAFLD ; hepatic inflammation ; fibrosis ; hepatic fibrosis ; diet