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Fructose-mediated effects on gene expression and epigenetic mechanisms associated with NAFLD pathogenesis

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Abstract

Nonalcoholic fatty liver disease (NAFLD) is a chronic, frequently progressive condition that develops in response to excessive hepatocyte fat accumulation (i.e., steatosis) in the absence of significant alcohol consumption. Liver steatosis develops as a result of imbalanced lipid metabolism, driven largely by increased rates of de novo lipogenesis and hepatic fatty acid uptake and reduced fatty acid oxidation and/or disposal to the circulation. Fructose is a naturally occurring simple sugar, which is most commonly consumed in modern diets in the form of sucrose, a disaccharide comprised of one molecule of fructose covalently bonded with one molecule of glucose. A number of observational and experimental studies have demonstrated detrimental effects of dietary fructose consumption not only on diverse metabolic outcomes such as insulin resistance and obesity, but also on hepatic steatosis and NAFLD-related fibrosis. Despite the compelling evidence that excessive fructose consumption is associated with the presence of NAFLD and may even promote the development and progression of NAFLD to more clinically severe phenotypes, the molecular mechanisms by which fructose elicits effects on dysregulated liver metabolism remain unclear. Emerging data suggest that dietary fructose may directly alter the expression of genes involved in lipid metabolism, including those that increase hepatic fat accumulation or reduce hepatic fat removal. The aim of this review is to summarize the current research supporting a role for dietary fructose intake in the modulation of transcriptomic and epigenetic mechanisms underlying the pathogenesis of NAFLD.

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Acknowledgements

The author thanks Drs. Gabriel Q. Shaibi (Arizona State University) and Richard M. Watanabe (University of Southern California) for comments on the manuscript.

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  1. Diabetes and Fibrotic Disease Unit, Translational Genomics Research Institute, 445 N 5th Street, Phoenix, AZ, 85004, USA

    Johanna K. DiStefano

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DiStefano, J.K. Fructose-mediated effects on gene expression and epigenetic mechanisms associated with NAFLD pathogenesis. Cell. Mol. Life Sci. 77, 2079–2090 (2020). https://doi.org/10.1007/s00018-019-03390-0

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