ABSTRACT
Different fasting regimens are known to promote health, mitigate chronic immunological disorders, and improve age-related pathophysiological parameters in animals and humans. Indeed, several clinical trials are currently ongoing using fasting as a potential therapy for a wide range of conditions. Fasting alters metabolism by acting as a reset for energy homeostasis. However, the molecular mechanisms underlying the beneficial effects of short-term fasting (STF) are still not well understood, particularly at the systems or multi-organ level. Here, we investigated the dynamic gene expression patterns associated with six periods of STF in nine different mouse organs. We cataloged the transcriptional dynamics within and between organs during STF and discovered differential temporal effects of STF among organs. Using gene ontology enrichment analysis, we identified an organ network sharing 37 common biological pathways perturbed by STF. This network incorporates the brain, liver, interscapular brown adipose tissue, and posterior-subcutaneous white adipose tissue, hence we named it the brain-liver-fats organ network. Using Reactome pathways analysis, we identified the immune system, dominated by T cell regulation processes, as a central and prominent target of systemic modulations during STF in this organ network. The changes we identified in specific immune components point to the priming of adaptive immunity and parallel the fine-tuning of innate immune signaling. Our study provides a comprehensive multi-organ transcriptomic profiling of mice subjected to multiple periods of STF, and adds new insights into the molecular modulators involved in the systemic immuno-transcriptomic changes that occur during short-term energy loss.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
We updated the title and corrected the abstract, as it contained a couple of errors.
ABBREVIATIONS
- STF
- Short-term fasting
- OB
- olfactory bulb
- BRN
- brain
- CBL
- cerebellum
- BST
- brainstem
- STM
- stomach
- LIV
- liver
- iBAT
- interscapular brown adipose tissue
- pgWAT
- perigonadal white adipose tissue
- psWAT
- posterior-subcutaneous white adipose tissue
- HVG
- highly-variable genes
- log2(x+1) NC
- log2 expression values
- HCA
- hierarchical clustering analysis
- FDR
- false discovery rate
- DEGs
- differentially expressed genes
- FC
- fold change
- log2FC
- log2 fold change
- GO
- Gene Ontology
- subcDEGs
- sub-clustered DEGs
- LitLabTM
- Acumenta Literature Lab
- MeSH
- Medical Subject Headings
- GH
- growth hormone
- IGF
- insulin-like growth factors
- BDNF
- brain-derived neurotropic factor
- NE
- norepinephrine