The role of sex-based differences in NASH regulation

Several recent studies have suggested the existence of a relationship between sex-based differences, liver injury, and cell survival in patients with non-alcoholic steatohepatitis (NASH). B cell lymphoma 6 (Bcl6), a nuclear transcription factor responsible for the regulation of sex-biased functional gene expression in the liver, has been linked to NASH.
PUBLISHED IN: Cells 2022

Comment:

Several recent studies have suggested the existence of a relationship between sex-based differences, liver injury, and cell survival in patients with non-alcoholic steatohepatitis (NASH). B cell lymphoma 6 (Bcl6), a nuclear transcription factor responsible for the regulation of sex-biased functional gene expression in the liver, has been linked to NASH.

This review aims to characterise the main molecular mechanisms and sex-biased functional differences controlling NASH, cell stress, and cell death. 

Key learnings:

Hepatic fat accumulation was found to be controlled by excessive calorie intake, fatty acid metabolism, blood cholesterol, and bile acid metabolism. Oxidative and endoplasmic reticulum stress also regulate the inflammation and hepatocyte death associated with NASH progression.

After confirmation in systemic gene-deficient mice models, both sex steroid hormones and Bcl6 were also found to be major players in the development of NASH. Oestrogen was found to be protective against inflammation and hepatic cell death, while Bcl6 contributed to the regulation of fatty acid metabolism. Bcl6 is further known to be a transcriptional regulator of hepatic sex-biased genes and may thus act alongside sex hormones to regulate cell stress and death in NASH. 

Future research should seek to clarify the sex-biased transcriptional network responsible for regulating NASH.

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Dr. S Duarte

Dr. S Duarte

Articles: 56

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