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The role of endocannabinoids in circadian disruption induced metabolic dysregulation

Award Number: R01DK119811
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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The role of endocannabinoids in circadian disruption induced metabolic dysregulation - ABSTRACT: Obesity and its co-morbid pathologies cardiovascular disease and diabetes are significant and growing public health problems. Obesity occurs as a result of interactions between multiple organs (e.g. liver, muscle, adipose), genetic factors, physiological factors (e.g. insulin, cytokines, and glucocorticoids), and environmental factors, particularly those associated with modern life (e.g. diet, lack of exercise, stress). Growing evidence suggests one of the most insidious of these environmental factors is the change in our circadian (daily) rhythms, driven by inappropriately timed exposure to light, shiftwork, and a 24h “always-on” society. Both epidemiologic and experimental data, including work from our own laboratory, support a role for circadian disruption in metabolic dysregulation. As such, manipulating environmental light-dark (LD) cycles could serve as a powerful tool to probe the mechanisms of environmentally driven metabolic dysregulation. Importantly, the mechanisms that link environmental circadian desynchronization (CD) to metabolic dysregulation remain unknown, limiting our mechanistic understanding of the role of circadian rhythms in the development of obesity. This proposal builds upon our published findings in mouse showing CD caused by shortening the LD cycle from 24h to 20h (LD10:10) results in weight gain, hyperinsulinemia, and other aspects of metabolic syndrome. Our focus now is to determine the mechanisms by which this environmental challenge leads to obesity. New data from our lab demonstrates that the endocannabinoid (eCB) system may be an important link between circadian rhythms and metabolic dysregulation. This is strengthened by recent data in humans that show rhythmic profiles of eCBs in the blood, that sleep/circadian disruption can alter these rhythms, and that over-activity in the eCB system is associated with obesity. The objective of this proposal is to mechanistically determine if the eCB system is an essential factor by which environmental and genetic circadian disruption contribute to changes in metabolic function, including increases in adiposity. We will use state-of-the art behavioral and metabolic phenotyping, gene expression and mass spectrometry to assess outcomes, and targeted pharmacology and tissue specific genetic manipulations to probe the mechanistic links between eCB signaling, circadian desynchronization, and metabolic dysregulation.


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: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF MASSACHUSETTS	101 COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	4/17/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $474,657 )
2023	2023	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	5	1/10/2023	NON-COMPETING CONTINUATION	$40,379
2023	2023	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	11/29/2022	SUPPLEMENT FOR EXPANSION	$70,867
2023	2023	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	11/28/2022	NON-COMPETING CONTINUATION	$363,411
														Subtotal = $474,657

Issue Date FY: 2022 ( Subtotal = $444,940 )
2022	2022	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	2/11/2022	SUPPLEMENT FOR EXPANSION	$41,150
2022	2022	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	12/17/2021	NON-COMPETING CONTINUATION	$363,410
2022	2022	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	4	4/7/2022	NON-COMPETING CONTINUATION	$40,380
														Subtotal = $444,940

Issue Date FY: 2021 ( Subtotal = $403,790 )
2021	2021	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	2/12/2021	NON-COMPETING CONTINUATION	$40,380
2021	2021	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	11/18/2020	NON-COMPETING CONTINUATION	$363,410
														Subtotal = $403,790

Issue Date FY: 2020 ( Subtotal = $403,790 )
2020	2020	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	2	6/8/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$156,054
2020	2020	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	2	6/2/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$1,155
2020	2020	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/8/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$404,945
2020	2019	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	5/7/2020	NEW	$0
2020	2019	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	1	6/8/2020	NEW	-$156,054
														Subtotal = $403,790

Issue Date FY: 2019 ( Subtotal = $388,584 )
2019	2019	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	1/31/2019	NEW	-$6,156
2019	2019	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	12/12/2018	NEW	$394,740
														Subtotal = $388,584

Grand Total All Awards = $2,115,761

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The role of endocannabinoids in circadian disruption induced metabolic dysregulation

Award Number: R01DK119811

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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