Sinton, M. C. , Hay, D. C. and Drake, A. J. (2019) Metabolic control of gene transcription in non-alcoholic fatty liver disease: the role of the epigenome. Clinical Epigenetics, 11, 104. (doi: 10.1186/s13148-019-0702-5) (PMID:31319896) (PMCID:PMC6637519)
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is estimated to affect 24% of the global adult population. NAFLD is a major risk factor for the development of cirrhosis and hepatocellular carcinoma, as well as being strongly associated with type 2 diabetes and cardiovascular disease. It has been proposed that up to 88% of obese adults have NAFLD, and with global obesity rates increasing, this disease is set to become even more prevalent. Despite intense research in this field, the molecular processes underlying the pathology of NAFLD remain poorly understood. Hepatic intracellular lipid accumulation may lead to dysregulated tricarboxylic acid (TCA) cycle activity and associated alterations in metabolite levels. The TCA cycle metabolites alpha-ketoglutarate, succinate and fumarate are allosteric regulators of the alpha-ketoglutarate-dependent dioxygenase family of enzymes. The enzymes within this family have multiple targets, including DNA and chromatin, and thus may be capable of modulating gene transcription in response to intracellular lipid accumulation through alteration of the epigenome. In this review, we discuss what is currently understood in the field and suggest areas for future research which may lead to the development of novel preventative or therapeutic interventions for NAFLD.
| Item Type: | Articles |
|---|---|
| Additional Information: | MCS is funded by a British Heart Foundation PhD studentship FS/16/54/32730. DCH was funded by the Chief Scientist Office (TCS/16/37). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Sinton, Dr Matthew |
| Authors: | Sinton, M. C., Hay, D. C., and Drake, A. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Clinical Epigenetics |
| Publisher: | BioMed Central |
| ISSN: | 1868-7075 |
| ISSN (Online): | 1868-7075 |
| Copyright Holders: | Copyright © 2019 The Authors |
| First Published: | First published in Clinical Epigenetics 11: 104 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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