# Determining The Role of Photic and Non-Photic Time Cues in Resetting Lipid Circadian Rhythms in Humans

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $886,157

## Abstract

Project Summary/Abstract
Circadian rhythm disruption is experienced by patients with Circadian Rhythm Sleep-Wake Disorders and
millions of shiftworkers worldwide, which may increase their risk of developing chronic health disorders including
cardiovascular disease. Treatment of circadian rhythm disruption requires appropriately-timed intervention to
either shift the circadian system earlier (advance) or later (delay). A Phase Response Curve (PRC) informs when
to administer the intervention, without which the disruption may either be prolonged due to inadequate phase
resetting or worsened due to shifting the system in the wrong direction. Currently, the field relies on the PRC for
resetting the melatonin rhythm as guide to reset the entire circadian system, despite the fact that circadian
rhythms are present in many other physiological features besides melatonin. Our preliminary data show that
there are robust circadian rhythms in circulating levels of total cholesterol and triglyceride in healthy young
individuals and that these rhythms can also be shifted. Our pilot studies further indicate that the timing of these
lipid rhythms may be more responsive to shifts in the timing of meals rather than light exposure. We have
constructed preliminary PRCs of these lipid rhythms in response to a combined stimulus of light exposure and
meals distributed across the 24-h day and detected robust phase advances and delays. Moreover, the shifts in
these lipid rhythms are larger than those for melatonin. We do not know, however, whether light exposure or
meal timing is the primary time cue for resetting these lipid rhythms. Without this knowledge, developing a
comprehensive treatment for circadian rhythm disruption of lipid rhythms that likely underlies the cardiometabolic
consequences of shiftwork, will remain difficult. The objective of this proposal is to construct three PRCs that
systematically examine the contribution of light and meal timing on resetting lipid circadian rhythms. Young
healthy adults will be randomized to three conditions: (1) bright light + 12-h meal window, (2) dim light + 12-h
meal window, and (3) dim light + 6.5-h meal window (time redistricted eating), each distributed across the 24-h
day. The primary outcomes include phase resetting of lipid and melatonin circadian rhythms measured under
each of the three conditions, and the area-under-the curve of the lipids during the 6.5-h time restricted eating.
The aims of the study are to: (1) determine if light is the primary time cue for resetting melatonin but not lipid
circadian rhythms, (2) determine if meal timing is the primary time cue for resetting lipid but not melatonin
circadian rhythms, and (3) evaluate the acute effects of eating across the 24-h day on circulating lipid levels. Our
work will be a comprehensive evaluation of how two daily events – light exposure and meals – synchronize lipid
circadian rhythms in humans. We expect our analytic paradigm to be a foundational resource ...

## Key facts

- **NIH application ID:** 10488652
- **Project number:** 5R01HL159207-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Shadab A Rahman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $886,157
- **Award type:** 5
- **Project period:** 2021-09-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10488652

## Citation

> US National Institutes of Health, RePORTER application 10488652, Determining The Role of Photic and Non-Photic Time Cues in Resetting Lipid Circadian Rhythms in Humans (5R01HL159207-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10488652. Licensed CC0.

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