Alternate-day fasting resolves liver fibrosis via hepatocyte eNOS signaling
Nitric oxide produced by hepatocytes during fasting blocks autophagy in stellate cells to halt fibrotic progression in mice.
Advanced science (Weinheim, Baden-Wurttemberg, Germany) · Wang X et al. · Paper published 27 Sep 2026
In mouse models and human fibrotic liver samples, researchers investigated how intercellular communication between hepatocytes and hepatic stellate cells controls fibrotic progression. The team found that eNOS expression drops in fibrotic livers, and deleting eNOS specifically in mouse hepatocytes worsened tissue injury and fibrosis. Alternate-day fasting reversed this decline by enhancing hepatocyte eNOS expression and reducing scarring in mice. Mechanistically, fasting suppressed the mitochondrial chaperone SDHAF4, halting complex II assembly and stimulating hepatocyte nitric oxide synthesis. Paracrine delivery of nitric oxide to hepatic stellate cells induced S-nitrosylation of ATG7 at cysteine 184, which restricted autophagic flux and prevented stellate cell transdifferentiation. Deleting hepatocyte eNOS completely abolished the metabolic and anti-fibrotic benefits of the fasting regimen in mice.
Why it matters
Dietary interventions such as intermittent fasting alter tissue maintenance, and mapping these intercellular pathways reveals how nutrient-sensing circuits can counteract chronic organ scarring. Targeting the downstream molecular modifications identified here could offer alternatives to strict dietary restrictions for maintaining liver health.
Caveats
The functional and genetic intervention experiments were conducted in mice, meaning the therapeutic relevance of this fasting-induced axis in human patients requires direct validation.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
A Hepatocyte-to-Stellate Cell Axis Couples Alternate-Day Fasting to Liver Fibrosis Resolution via ATG7 S-Nitrosylation
Wang X, Zeng M, Sun C et al.
Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 27 Sep 2026 · Peer-reviewed
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