Why severe fatty liver leads to liver damage

[Joachim]

In hepatic steatosis, hepatocytes "die," resulting in liver damage. Severe steatosis increases hepatocellular deaths, thus aggravating liver damage. The mechanism is unclear. Using mice, we show that mild steatosis causes apoptosis whereas severe steatosis predominantly causes necroptosis leading to cell rupture. This induces strong inflammation and new cell death, producing further liver damage. We reveal the transcription factor ATF3 to be involved in this process. Our results are expected to contribute to therapeutic method development.

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