# Balance of sleep and circadian metabolic switches in Drosophila

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $504,417

## Abstract

PROJECT SUMMARY
 Sleep loss is increasingly recognized as a significant risk factor in numerous metabolic diseases such
 as diabetes, obesity, metabolic syndrome, cancer, and cardiometabolic disorders. Clinical and model studies
 have confirmed negative metabolic effects of sleep loss. Intriguingly, sleep loss also dampens peripheral
 rhythms in human populations, which raises the question of whether the metabolic-sleep connection is
 mediated through circadian rhythms. Time-dependent analysis of metabolic changes has revealed large-scale
 oscillations in metabolite pools through the course of the circadian day in humans and other model systems
 such as rodents and flies. Disruption of the molecular clock, either genetically or through dietary intervention
 such as high-fat diet or mis-timed restricted feeding, causes insulin resistance and a lack of so-called
 `metabolic flexibility', phenotypes shared with sleep loss. We hypothesize that effects of reduced sleep on
 metabolism are mediated through changes in rhythms of energetic and redox metabolic pathways.
 One major limitation in gleaning mechanistic understanding of the sleep-circadian-metabolism
 connection is difficulty in measuring metabolic flux at different times of day in vivo. Our team has developed an
 innovative model of circadian flux using Drosophila melanogaster (fruit fly). Furthermore, dietary manipulations,
 such as time-restricted feeding in the active period or caloric restriction, maintain amplitudes in metabolic
 cycles in face of circadian disruption and have been associated with cardio-metabolic health in flies. In this
 proposal, we will exploit the genetic flexibility of D. melanogaster to test the above hypothesis in the following
 related but independent aims:
 Aim 1: Determine the impact of sleep loss on metabolic rhythms.
 Impact: An impact of sleep loss on metabolic oscillations will clarify the approach towards understanding how
 circadian rhythms and sleep, each of which is currently studied independently, affect metabolism.
 Aim 2: Determine if nutritional challenge exacerbates the metabolic effects of sleep loss in a time-of-
 day specific manner.
 Impact: These studies will provide direct mechanistic insights into the origin of metabolic imbalance which
 has only been inferred in studies to date. Future pharmacological or behavioral interventions can be targeted
accordingly.
 Aim 3: Determine if time-restricted feeding can mitigate effects of sleep deprivation on metabolism.
 Impact: Demonstration that dietary manipulation mitigates negative metabolic consequences of sleep loss
has the potential for interventional applicability in at risk real-world human populations.

## Key facts

- **NIH application ID:** 9995477
- **Project number:** 5R01DK120757-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** AMITA SEHGAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $504,417
- **Award type:** 5
- **Project period:** 2019-08-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995477

## Citation

> US National Institutes of Health, RePORTER application 9995477, Balance of sleep and circadian metabolic switches in Drosophila (5R01DK120757-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9995477. Licensed CC0.

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