# Regulation of circadian physiology by rhythmic food intake and the mTOR pathway

> **NIH NIH R01** · TEXAS A&M UNIVERSITY · 2022 · $370,896

## Abstract

PROJECT SUMMARY
Nearly every mammalian cell harbors a timekeeping mechanism, the circadian clock, that drives overt rhythms
in gene expression to coordinate the daily activity of biochemical and metabolic pathways. Consistent with the
large number of biological functions controlled by the circadian clock, disruption of rhythmic gene expression
leads to the development of a wide range of disorders that include metabolic diseases, cardiovascular
disorders and cancer. Moreover, most commonly used drugs in the United States directly target the products of
rhythmically expressed genes. For these reasons, characterizing the mechanisms underlying rhythmic gene
expression is critical to not only understand how clock dysfunction leads to pathological conditions, but also to
optimally time pharmacological treatment. Rhythmic gene expression is thought to be primarily regulated by
the molecular circadian clock found in every mammalian cell. However, increasing evidences from our lab and
others suggest that environmental signals like feeding rhythms generate 24-hour rhythms in gene expression
without involving the circadian clock oscillation. In Preliminary Studies, we show that the amplitude of feeding
rhythms controls the rhythmic expression of more than 2000 genes in mouse liver. Surprisingly, this effect on
gene expression does not seem to directly involve the hepatic circadian clock, which continues to exhibit
normal oscillations in core clock gene expression. Rather, our preliminary data suggest that rhythms in gene
expression rely on the rhythmic activity of the nutrient-sensing kinase mTOR. This proposal builds upon these
new exciting data and the proposed experiments will determine if feeding rhythms regulate rhythmic gene
expression by (1) controlling the rhythmic activity of mTOR signaling pathway, and (2) regulating the rhythmic
activity of metabolic transcription factors. Results from these experiments are expected to uncover novel and
important mechanisms for the regulation of rhythmic gene expression in mammals, and to provide a new
conceptual framework for how biological functions are synchronized to environmental cycles and coordinated
between tissues. They are also anticipated to lead to the development of novel strategies for advancements in
chronotherapy and for the restoration of rhythmic gene expression in humans showing poor circadian rhythms
like shift-workers and elders.

## Key facts

- **NIH application ID:** 10367363
- **Project number:** 1R01DK128133-01A1
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** Jerome Menet
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $370,896
- **Award type:** 1
- **Project period:** 2022-02-25 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367363

## Citation

> US National Institutes of Health, RePORTER application 10367363, Regulation of circadian physiology by rhythmic food intake and the mTOR pathway (1R01DK128133-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10367363. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*