# Circadian Mechanisms of Hedonic Feeding in Obesity

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2021 · $41,249

## Abstract

Project Summary
The circadian clock is an auto-regulatory transcription feedback loop present in the brain and peripheral tissues
that coordinates sleep/wake and physiology in anticipation of the rising of the sun each day. Epidemiologic,
clinical and genetic studies have shown clock dysregulation contributes to both obesity and its metabolic co-
morbidities. Recently, we have shown that abrogation of the core molecular clock component BMAL1 in
hypothalamic hunger neurons leads to increased feeding at the wrong phase of the day/night cycle and causes
impaired glucose tolerance, a hallmark of diabetes. AgRP neuron transcriptomics further identify circadian
regulation of dopaminergic neurotransmitter synapse, indicating that clock disruption may lead to alterations in
both the hedonic and homeostatic control of feeding. With a focus on understanding the mechanisms linking
circadian systems to hedonic feeding, I have generated new data demonstrating that disruption of the molecular
clock in dopaminergic neurons of the classical reward-promoting ventral tegmental area (VTA) results in
hyperphagia of palatable high fat food and accelerates diet-induced obesity, hyperglycemia, impaired oxidative
metabolism by respirometry, altered sleep patterns, and decreased daytime open field behavior. The scientific
rationale underlying my present proposal is that the circadian clock modulates time-of-day dependent feeding
and metabolic processes through the regulation of food-associated reward within midbrain dopaminergic
neurons. This proposal seeks to contribute new insight into how neuronal clocks synchronize behavioral and
transcriptional rhythms to impact physiology, findings which have broad implications for the treatment and
prevention of sleep-loss related disorders of obesity, metabolic syndrome, and type 2 diabetes mellitus.

## Key facts

- **NIH application ID:** 10315379
- **Project number:** 1F31DK130589-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Nathan James Waldeck
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $41,249
- **Award type:** 1
- **Project period:** 2021-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315379

## Citation

> US National Institutes of Health, RePORTER application 10315379, Circadian Mechanisms of Hedonic Feeding in Obesity (1F31DK130589-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10315379. Licensed CC0.

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