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Analysis of Lipolytic Trafficking in Adipocytes.

Award Number: R01DK076629
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2009
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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View Award Description

Analysis of Lipolytic Trafficking in Adipocytes. - Project Summary/Abstract Disruption of cellular neutral lipid metabolism promotes the progression of obesity, diabetes, fatty liver disease, and cancer. The long-term scientific goal of the project is to understand the molecular mechanisms that control lipid storage and mobilization in order to identify novel points for therapeutic intervention. ABHD5 regulates cellular lipid metabolism, including PNPLA2/ATGL, the rate-limiting triglyceride lipase in key metabolic tissues. Nonetheless, the mechanisms by which ABHD5, a protein lacking enzymatic activity, activates PNPLA2 (and other PNPLAs) remains an important mystery. We hypothesize that the remodeling of biological membranes is a general mechanism by which ABHD5 regulates enzyme access to membrane-delimited neutral lipid substrates. Mechanistically, we hypothesize that ligand binding stabilizes ABHD5 molecular and macromolecular conformations that target and alter membrane biophysical properties (tension and curvature) to allow the lipase access to specific substrates sequestered within lipid droplets (LDs). We will test this hypothesis using novel chemical probes of ABHD5 and informative genetic mutants in live adipocytes (Aim 1). We will directly assess the impact ABHD5 on the biophysical properties of membranes in model LD systems using an array of high resolution and high throughput approaches (Aim 2). These Aims are designed to be highly complementary and to provide strong cross- validation between experimental platforms. In addition, we present data demonstrating that ABHD5 is targeted to specific subcellular sites where LDs form upon fatty acid supplementation. Furthermore, the interaction of ABHD5 with PLIN5, driven by the ABHD5 ligand oleoyl-CoA, facilitates LD formation. Aim 3 will dissect the biochemical pathways promoted by ABHD5/PLIN5 complexes and, in concert with Aim 2, evaluate the impact of this interaction on the biophysical properties of model membranes. ABHD5 is emerging as a compelling therapeutic target for metabolic diseases and cancer. The results of this project will provide new insights into specific mechanisms by which ABHD5 regulates fatty acid flux at the cytosol/LD interface.


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: 2026 ( Subtotal = $0 )
2026	2025	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	16	2/18/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $463,992 )
2025	2025	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	16	4/17/2025	NON-COMPETING CONTINUATION	$463,992
														Subtotal = $463,992

Issue Date FY: 2024 ( Subtotal = $445,433 )
2024	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	15	4/5/2024	NON-COMPETING CONTINUATION	$417,592
2024	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	15	5/20/2024	NON-COMPETING CONTINUATION	$27,841
														Subtotal = $445,433

Issue Date FY: 2023 ( Subtotal = $463,992 )
2023	2023	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	3/24/2023	NON-COMPETING CONTINUATION	$463,992
														Subtotal = $463,992

Issue Date FY: 2022 ( Subtotal = $463,992 )
2022	2022	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	13	3/31/2022	NON-COMPETING CONTINUATION	$46,403
2022	2022	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	2/24/2022	NON-COMPETING CONTINUATION	$417,589
														Subtotal = $463,992

Issue Date FY: 2021 ( Subtotal = $463,992 )
2021	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	12	3/22/2021	COMPETING CONTINUATION	$463,992
2021	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	12	9/22/2021	COMPETING CONTINUATION	$275,902
2021	2020	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	11	9/22/2021	NON-COMPETING CONTINUATION	-$275,902
2021	2020	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	3/16/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $463,992

Issue Date FY: 2020 ( Subtotal = $439,846 )
2020	2020	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	3/12/2020	NON-COMPETING CONTINUATION	$439,846
														Subtotal = $439,846

Issue Date FY: 2019 ( Subtotal = $439,846 )
2019	2019	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	4/2/2019	NON-COMPETING CONTINUATION	$439,846
														Subtotal = $439,846

Issue Date FY: 2018 ( Subtotal = $563,133 )
2018	2018	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	9	8/24/2018	SUPPLEMENT FOR EXPANSION	$47,000
2018	2018	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	2/27/2018	NON-COMPETING CONTINUATION	$464,517
2018	2018	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	9	4/26/2018	NON-COMPETING CONTINUATION	$51,616
														Subtotal = $563,133

Issue Date FY: 2017 ( Subtotal = $529,633 )
2017	2017	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	8	3/24/2017	SUPPLEMENT FOR EXPANSION	$86,727
2017	2017	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	8	6/15/2017	NON-COMPETING CONTINUATION	$44,292
2017	2017	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	2/28/2017	NON-COMPETING CONTINUATION	$398,614
														Subtotal = $529,633

Issue Date FY: 2016 ( Subtotal = $383,750 )
2016	2016	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	7	4/28/2016	COMPETING CONTINUATION	$383,750
2016	2014	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	4/22/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $383,750

Issue Date FY: 2014 ( Subtotal = $311,600 )
2014	2014	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	6/17/2014	NON-COMPETING CONTINUATION	$311,600
														Subtotal = $311,600

Issue Date FY: 2013 ( Subtotal = $300,694 )
2013	2013	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	6/24/2013	NON-COMPETING CONTINUATION	$300,694
														Subtotal = $300,694

Issue Date FY: 2012 ( Subtotal = $311,600 )
2012	2012	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	5/17/2012	NON-COMPETING CONTINUATION	$311,600
														Subtotal = $311,600

Issue Date FY: 2011 ( Subtotal = $342,000 )
2011	2011	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	7/8/2011	COMPETING CONTINUATION	$342,000
2011	2011	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	3	7/25/2011	COMPETING CONTINUATION	$0
2011	2010	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Trans-NIH Recovery Act Research Support	002	2	7/25/2011	NON-COMPETING CONTINUATION	$0
2011	2010	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Trans-NIH Recovery Act Research Support	001	2	7/8/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $342,000

Issue Date FY: 2010 ( Subtotal = $266,000 )
2010	2010	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Trans-NIH Recovery Act Research Support	000	2	6/23/2010	NON-COMPETING CONTINUATION	$266,000
														Subtotal = $266,000

Issue Date FY: 2009 ( Subtotal = $316,416 )
2009	2009	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Trans-NIH Recovery Act Research Support	000	1	5/26/2009	NEW	$316,416
														Subtotal = $316,416

Grand Total All Awards = $6,505,919

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Analysis of Lipolytic Trafficking in Adipocytes.

Award Number: R01DK076629

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2009

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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