# Aryl hydrocarbon receptor regulation of energy metabolism

> **NIH NIH R15** · SOUTHERN ILLINOIS UNIVERSITY SCH OF MED · 2024 · $445,500

## Abstract

Metabolic syndrome and diabetes are pandemic in modern society. Humans with increased an
elevated body burden of certain lipophilic xenobiotics such as dioxins are at increased risk for
type 2 diabetes and metabolic syndrome. These anthropogenic substances exert their effects
through activation of aryl hydrocarbon receptor (AhR). Results under the previous award
present a compelling argument that disruption of circadian rhythmicity, particularly
desynchronization of the central clock from those in metabolically important organs, occurs
subsequent to long-term AhR activation, in a sex-specific manner. Metabolic syndrome
develops in mice that have a disrupted circadian clock, and diabetic mice display marked
alterations in circadian rhythms. Chronic AhR activation causes a similar disruption in rhythms in
liver and adipose tissue. This proposal thus seeks to alleviate AhR-induced metabolic
dysfunction using a treatment that involves bolstering circadian clock function. Previous findings
also demonstrate that AhR regulation of adipose tissue is more important in females, and that
female adipose tissue has significant impact in regulating systemic glucose metabolism. We
hypothesize that restricted feeding can regulate can restore depleted rhythms in adipose
tissue function and rescue metabolism from the detrimental effects of chronic AhR
activation. Further we hypothesize that estrogen/AhR interactions underlie adipose
regulation of systemic metabolism in females. The proposal combines approaches that
examine systemic metabolic parameters and behavioral circadian rhythms and molecular
studies that focus on mechanisms of AhR/estrogen interactions. Specific aim I explores
restricted feeding as a mechanism to reset clock function after its ablation by chronic AhR
activation. Aim II explores molecular mechanisms of AhR interactions with estrogen signaling
specifically in female adipose tissue. The project provides a framework for training
undergraduate, graduate and medical students in preparation for careers in the biomedical
sciences. The proposal highlights a novel mechanism for xenobiotic action in the
development of metabolic syndrome, explores a biological basis for sex-specific
therapeutics, and provides insight into the potential for chronotherapy as a treatment for
diabetes and metabolic syndrome.

## Key facts

- **NIH application ID:** 10974201
- **Project number:** 2R15ES030556-02
- **Recipient organization:** SOUTHERN ILLINOIS UNIVERSITY SCH OF MED
- **Principal Investigator:** Shelley A Tischkau
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $445,500
- **Award type:** 2
- **Project period:** 2020-09-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10974201

## Citation

> US National Institutes of Health, RePORTER application 10974201, Aryl hydrocarbon receptor regulation of energy metabolism (2R15ES030556-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10974201. Licensed CC0.

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