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Aryl hydrocarbon receptor regulation of energy metabolism

Award Number: R15ES030556
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Aryl hydrocarbon receptor regulation of energy metabolism - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $445,500 )
2024	2024	SOUTHERN ILLINOIS UNIVERSITY SCHOOL OF MEDICINE	801 N RUTLEGE	SPRINGFIELD	IL	62794	SANGAMON	USA	Environmental Health	000	2	7/23/2024	COMPETING CONTINUATION	$445,500
2024	2024	SOUTHERN ILLINOIS UNIVERSITY SCHOOL OF MEDICINE	801 N RUTLEGE	SPRINGFIELD	IL	62794	SANGAMON	USA	Environmental Health	002	2	8/28/2024	COMPETING CONTINUATION	$8,751
2024	2020	SOUTHERN ILLINOIS UNIVERSITY SCHOOL OF MEDICINE	801 N RUTLEGE	SPRINGFIELD	IL	62794	SANGAMON	USA	Environmental Health	001	1	8/28/2024	NEW	-$8,751
														Subtotal = $445,500

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	SOUTHERN ILLINOIS UNIVERSITY SCHOOL OF MEDICINE	801 N RUTLEGE	SPRINGFIELD	IL	62794	SANGAMON	USA	Environmental Health	000	1	8/30/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $442,500 )
2020	2020	SOUTHERN ILLINOIS UNIVERSITY	801 N RUTLEDGE ST FL 2	SPRINGFIELD	IL	62702	SANGAMON	USA	Environmental Health	000	1	8/14/2020	NEW	$442,500
2020	2020	SOUTHERN ILLINOIS UNIVERSITY	801 N RUTLEDGE ST FL 2	SPRINGFIELD	IL	62702	SANGAMON	USA	Environmental Health	001	1	8/19/2020	NEW	$0
														Subtotal = $442,500

Grand Total All Awards = $888,000

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Aryl hydrocarbon receptor regulation of energy metabolism

Award Number: R15ES030556

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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