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Adipose tissue plasticity in health and disease

Award Number: R01DK122804
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: 07/01/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Adipose tissue plasticity in health and disease - Abstract The ability of adipose tissue to handle fluctuations in nutrient availability, by dynamically expanding and contracting, is critical for survival. However, dysregulation of this process can lead to lipodystrophy, obesity and dysregulated energy homeostasis. Various factors influence adipocyte plasticity, including anatomical location, neighboring immune cells, the vasculature and the surrounding extracellular matrix (ECM). While matrix metalloproteinases (MMPs) have been postulated to participate in the remodeling of the ECM, most attention has focused on the type I collagen-rich stromal/interstitial ECM. However, mature adipocytes are surrounded by a specialized form of ECM, termed the basement membrane, that mechanically regulates cell shape. Without modifying basement membrane assembly or remodeling, changes in adipocyte shape and storage capacity would not be possible. Nevertheless, the role of the basement membrane in regulating fat metabolism and function are almost uniformly overlooked. This proposal will seek to document the dynamic changes in MT1-MMP-mediated basement membrane remodeling in both physiological and pathological states while identifying the regulatory pathways involved in this process. Aim 1 will provide a characterization of basement membrane remodeling and corresponding alterations in adipose inflammation, glucose/insulin homeostasis transcriptional events. Aim 2 will elucidate the mechanism underlying MT1-MMP regulation by exploring its trafficking to the plasma membrane by insulin. Aim 3 will determine the physiological consequence of impaired adipose plasticity in states of obesity by investigating adipose-specific conditional KO mice of MT1-MMP. The experiments outlined in this proposal are designed to explore and expand insights into the role and regulation of the basement membrane in adipose tissue. The work proposed here lays the groundwork for future studies into how the basement membrane is modified in adipose tissue, and has potential to help develop therapeutic targets in the fight against obesity.


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 CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	9/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $599,749 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	5/1/2023	NON-COMPETING CONTINUATION	$599,749
														Subtotal = $599,749

Issue Date FY: 2022 ( Subtotal = $600,159 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/3/2022	NON-COMPETING CONTINUATION	$600,159
														Subtotal = $600,159

Issue Date FY: 2021 ( Subtotal = $602,878 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/19/2021	NON-COMPETING CONTINUATION	$602,878
														Subtotal = $602,878

Issue Date FY: 2020 ( Subtotal = $618,916 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/24/2020	NEW	$618,916
														Subtotal = $618,916

Grand Total All Awards = $2,421,702

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Adipose tissue plasticity in health and disease

Award Number: R01DK122804

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: 07/01/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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