title: Glucocorticoids and non-alcoholic fatty liver disease.
abstract: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the global obesity and metabolic disease epidemic and is rapidly becoming the leading cause of liver cirrhosis and indication for liver transplantation worldwide. The hallmark pathological finding in NAFLD is excess lipid accumulation within hepatocytes, but it is a spectrum of disease ranging from benign hepatic steatosis to steatohepatitis through to fibrosis, cirrhosis and risk of hepatocellular carcinoma. The exact pathophysiology remains unclear with a multi-hit hypothesis generally accepted as being required for inflammation and fibrosis to develop after initial steatosis. Glucocorticoids have been implicated in the pathogenesis of NAFLD across all stages. They have a diverse array of metabolic functions that have the potential to drive NAFLD acting on both liver and adipose tissue. In the fasting state, they are able to mobilize lipid, increasing fatty acid delivery and in the fed state can promote lipid accumulation. Their action is controlled at multiple levels and in this review will outline the evidence base for the role of GCs in the pathogenesis of NAFLD from cell systems, rodent models and clinical studies and describe interventional strategies that have been employed to modulate glucocorticoid action as a potential therapeutic strategy.
authors.affiliation: Oxford Centre for Diabetes Endocrinology & Metabolism (OCDEM), Churchill Hospital, Headington, Oxford, OX3 7LJ, UK.
authors.forename: Conor P
authors.initials: CP
authors.lastname: Woods
authors.affiliation: Oxford Centre for Diabetes Endocrinology & Metabolism (OCDEM), Churchill Hospital, Headington, Oxford, OX3 7LJ, UK.
authors.forename: Jonathon M
authors.initials: JM
authors.lastname: Hazlehurst
authors.affiliation: Oxford Centre for Diabetes Endocrinology & Metabolism (OCDEM), Churchill Hospital, Headington, Oxford, OX3 7LJ, UK. Electronic address: Jeremy.tomlinson@ocdem.ox.ac.uk.
authors.forename: Jeremy W
authors.initials: JW
authors.lastname: Tomlinson
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D001066:Appetite / Q000502:physiology; D005938:Glucocorticoids / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D005938:Glucocorticoids
keywords: Adipose tissue; Cortisol; Glucocorticoid Receptor; Glucocorticoids; NAFLD; NASH