# Investigating the metabolic effects and de novo establishment of circadian timing differences between brain and liver

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2024 · $78,892

## Abstract

Project Summary/Abstract
Circadian disruptions are strongly associated with metabolic dysfunction, yet the mechanisms by which the
circadian and metabolic systems influence one another are unclear. Elucidating the relationship between the
two systems is especially important because of the prevalence of both metabolic and circadian disruptions and
the safety and tractability of the circadian system as a therapeutic target. To address this need, the proposed
work will determine whether changes to the relative timing of the circadian oscillators in the brain, which
houses the central clock (the suprachiasmatic nucleus, or SCN) and controls feeding and metabolic rate, and
liver, which controls both glucose and fat metabolism, underlie light- and diet-induced metabolic disorders. This
work will test the hypothesis that relative timing of the brain and the liver is disrupted by aberrant light exposure
and/or maladaptive feeding, and that this relative timing is established under typical conditions by tissue-
specific period changes stemming from circadian transcriptional regulation differences. The proposed work will
test these hypotheses using mouse models of clock disruption, obesogenic diets, and altered light timing to
investigate the relative timing of the brain and liver and how that timing can be tuned. The resulting
understanding of the origin and plasticity of the endogenous relative timing between the two tissues will provide
a framework for prevention and intervention from metabolic disease with circadian etiology.
The fellowship training plan developed around the research project described above will combine skills that I
have developed during my Ph.D. studies with the expertise of the laboratory of my sponsor. Specifically, I will
take advantage of my extensive experience with circadian biology, particularly with regards to the SCN and its
influence over physiological rhythms, as well as my training in the production, maintenance, data acquisition,
and analysis of organotypic tissue cultures expressing circadian clock gene reporters. I will apply these skills to
the metabolic research questions described above by taking advantage of the expertise in the Lazar Lab in
metabolic and liver health and functional genomic techniques. The synergistic combination of my past
experience and the expertise of the Lazar Lab will thoroughly broaden and deepen my scientific and technical
skillset, which will aid me in my preparation for becoming an independent investigator. The proposed
experiments will be carried out at the world-class University of Pennsylvania, which will provide technical
support in the form of collaboration, expertise, and core facilities as well as career development support in the
form of training sessions, guidance, and networking opportunities.

## Key facts

- **NIH application ID:** 10814927
- **Project number:** 5F32DK132830-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Michael Tackenberg
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $78,892
- **Award type:** 5
- **Project period:** 2022-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10814927

## Citation

> US National Institutes of Health, RePORTER application 10814927, Investigating the metabolic effects and de novo establishment of circadian timing differences between brain and liver (5F32DK132830-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10814927. Licensed CC0.

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