Uncovering shared and tissue-specific molecular adaptations to intermittent fasting in liver, brain, and muscle.
Level 5 - mechanism / opinion, no new human data
Preclinical animal research
PubMed 41995076 · doi:10.7554/eLife.107332
What was done
Male C57BL/6 mice were subjected to a 16-hour daily fasting regimen (IF16) for 4 months. The researchers measured systemic metabolic markers (blood glucose, HbA1c, cholesterol, ketone bodies) and performed comprehensive transcriptomic and proteomic profiling across three tissues: liver, skeletal muscle, and cerebral cortex.
What was found
The abstract reports directional pathway and marker alterations without quantitative numbers or effect sizes. Intermittent fasting reduced blood glucose, HbA1c, and cholesterol while increasing ketone bodies. Tissue-specific proteomic profiles revealed: - Liver: Upregulated fatty acid oxidation, ketogenesis, and glycan degradation; downregulated steroid hormone and cholesterol metabolism. - Skeletal muscle: Upregulated pyruvate metabolism, fatty acid biosynthesis, and AMPK signaling; downregulated oxidative phosphorylation and thermogenesis. - Cerebral cortex: Upregulated autophagy, PPAR signaling, and metabolic pathways; downregulated TGF-beta and p53 signaling. - Shared: Serpin A1c was the only protein consistently upregulated across all three tissues. Transcriptomic and proteomic expression showed only partial concordance.
Why it matters
This study provides an integrated multi-tissue map of the molecular adaptations to time-restricted feeding in mice, identifying Serpin A1c as a candidate mediator of systemic metabolic flexibility.
Limits
The study was conducted exclusively in male mice, limiting generalizability to females and humans. Sample size (n) and exact numerical effect sizes are not reported in the abstract. Functional validation of Serpin A1c was not described.
Cited by
- supports Tissues like the liver, brain, and muscle are sensitive to fasting-induced autophagy, whereas blood cells have a restricted autophagy response to fasting.