GEO series

The outcomes of caloric restriction are driven by enhanced glucocorticoid rhythms.

GSE248866 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 114 samples Submitted 2025/11/04 Platform GPL17021Platform GPL34290Platform GPL24247

Summary

Caloric restriction extends lifespan and healthspan across species, with feeding times synchronized to circadian rhythms further maximizing its benefits. However, the mechanisms linking diet, diurnal rhythms, and lifespan are not fully understood. In mice, the time point most strongly tied to dietary effects on lifespan coincides with the peak of glucocorticoid secretion (ZT12, lights-off). Caloric restriction raises circulating glucocorticoid hormone levels, but their functional relevance remains untested. We show that the glucocorticoid receptor (GR) is critical for the effects of caloric restriction. Hepatocyte-specific GR mutant mice fail to respond to caloric restriction indicating that increased glucocorticoid amplitudes support its benefits. Using multiomics techniques in murine liver, we find that nutrient deprivation elicits a nuclear switch from active STAT signaling to increased FOXO1 activity, enabling the GR to activate a unique diet-specific gene expression program. Taken together, our results suggest that glucocorticoid rhythms are crucial for caloric restriction-induced metabolic reprogramming.

Published in

Hepatic metabolic reprogramming in male mice during short-term caloric restriction involves enhanced glucocorticoid rhythms

Makris K, Fonda V, Ramadhani FF et al. · Nature communications 2025 · PMID 41381594 · doi:10.1038/s41467-025-67228-z

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Direct links to NCBI, no account and no request form: the whole study as GSE248866_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 114 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1046130 and SRA study SRP474710. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41381594) ↗

Study design

11 conditions, mostly with about 4 replicates each

NRF_ZT8_WT ×4 NRF_ZT8_GRLKO ×4 NRF_ZT12_WT ×4 NRF_ZT12_GRLKO ×4 NRF_ZT16_WT ×4 NRF_ZT20_WT ×4 NRF_ZT0_WT ×3 NRF_ZT0_GRLKO ×3 +4 more

Supports a between-group comparison across 39 samples.

11 replicated groups read from the first 40 of 114 sample titles; they account for 39 of them. Check it against the sample list below before relying on it.

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