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Mechanisms Behind NAFLD: a System Genetics Perspective

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Abstract

Purpose of Review

To summarize the key factors contributing to the onset and progress of nonalcoholic fatty liver disease (NAFLD) and put them in a system genetics context. We particularly focus on how genetic regulation of hepatic lipids contributes to NAFLD.

Recent Findings

NAFLD is characterized by excessive accumulation of fat in the liver. This can progress to steatohepatitis (inflammation and hepatocyte injury) and eventually, cirrhosis. The severity of NAFLD is determined by a combination of factors including obesity, insulin resistance, and lipotoxic lipids, along with genetic susceptibility. Numerous studies have been conducted on large human cohorts and mouse panels, to identify key determinants in the genome, transcriptome, proteome, lipidome, microbiome and different environmental conditions contributing to NAFLD.

Summary

We review common factors contributing to NAFLD and put them in a systems genetics context. In particular, we describe how genetic regulation of liver lipids contributes to NAFLD. The combination of an unhealthy lifestyle and genetic predisposition increases the likelihood of accumulating lipotoxic specie lipids that may be one of the driving forces behind develo** severe forms of NAFLD.

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Acknowledgements

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Shirin Pourteymour has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 801133.

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  1. Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Blindern, PO Box 1046, 0317, Oslo, Norway

    Shirin Pourteymour, Christian A. Drevon, Knut Tomas Dalen & Frode A. Norheim

  2. Vitas Ltd. Oslo Science Park, Oslo, Norway

    Christian A. Drevon

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Pourteymour, S., Drevon, C.A., Dalen, K.T. et al. Mechanisms Behind NAFLD: a System Genetics Perspective. Curr Atheroscler Rep 25, 869–878 (2023). https://doi.org/10.1007/s11883-023-01158-3

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