Friday, October 31, 2025 10/31/2025

Physiological Role of Dedifferentiating Dermal Adipose Tissue

Award Number: R01DK131537
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: 12/01/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2025

Group Awards By:

View Award Description

Physiological Role of Dedifferentiating Dermal Adipose Tissue - Abstract Physiological Role of De-differentiating Dermal Adipose Tissue Adipose tissue fibrosis is an integral component of dysfunctional fat tissue. This fibrosis exerts detrimental effects on local metabolic responses within adipose tissue, in addition to initiating maladaptive systemic responses. The exact cause(s) of fibrosis in adipose tissue are still a matter of debate and as such, are not well defined. Here, we aim to focus on “dermal adipose tissue fibrosis”, primarily due to its 1) ease of accessibility, 2) our new genetic mouse models that we generated to specifically examine dermal adipose tissue dysfunction and, 3) our initial observation that identified extensive dermal adipocyte differentiation and de-differentiation. We believe that the latter processes are a key aspect of the pathological road to adipose tissue fibrosis. Dermal adipose tissue is skin-associated fat located directly under the reticular dermis. Compared to other well-defined fat pads, dermal adipose tissue displays a high degree of plasticity. Under a variety of physiological conditions, dermal adipose tissue has the capacity to either rapidly and locally expand, or reduce its volume. Our in vivo preliminary studies showed that dermal adipose tissue is negatively associated with collagen production in skin fibroblasts. Importantly, more recent studies in our laboratory identified that the highly dynamic nature of dermal adipocytes allows them to 1) undergo de-differentiation into pre-adipocytes or, 2) convert into alpha-SMA-positive myofibroblasts (when examined in a bleomycin-induced fibrosis model). Here, we propose to examine the following hypothesis: that the adipocyte itself is the major player in preventing adipose tissue fibrosis in response to a metabolic challenge of high fat diet feeding, or bleomycin induction. We will address our hypothesis in three Specific Aims: I) We will retain fat cells in a fully differentiated state, by either ectopically exposing dermal adipocytes to PPARgamma agonists. In parallel, we aim to genetically overexpress PPARgamma then assess the impact on the fibrotic response. In addition to this, we will examine the impact of a complete elimination of adipocytes upon the local fibrotic response in the skin. II) Through lineage tracing, we aim to genetically label and track mature adipocytes as they de-differentiate into pre-adipocytes. Some of these pre- adipocytes can convert to myofibroblasts. We have developed a genetic approach to selectively eliminate myofibroblasts that originate from mature adipocytes. This will allow us, for the first time, to examine the functional relevance of these adipocyte-derived myofibroblasts towards the fibrotic response in adipose tissue. III) With a newly developed “Split Cre” system, we take advantage of a dual promoter system that ensures expression uniquely in the dermal adipocyte. We will manipulate leptin and adiponectin levels locally, then address the impact of local adipokine action in the microenvironment of the dermal adipose tissue on the fibrotic response. While we focus on dermal adipose tissue, results from the proposed studies will also have a profound impact on the understanding of the fibrotic response in other fat depots.


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 = $518,240 )
2025	2025	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	11/22/2024	NON-COMPETING CONTINUATION	$466,417
2025	2025	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	7/16/2025	NON-COMPETING CONTINUATION	$51,823
														Subtotal = $518,240

Issue Date FY: 2024 ( Subtotal = $497,510 )
2024	2024	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	11/29/2023	NON-COMPETING CONTINUATION	$466,417
2024	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	5/17/2024	NON-COMPETING CONTINUATION	$31,093
														Subtotal = $497,510

Issue Date FY: 2023 ( Subtotal = $518,240 )
2023	2023	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	2/2/2023	NON-COMPETING CONTINUATION	$51,823
2023	2023	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	11/30/2022	NON-COMPETING CONTINUATION	$466,417
														Subtotal = $518,240

Issue Date FY: 2022 ( Subtotal = $518,240 )
2022	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	11/25/2021	NEW	$518,240
														Subtotal = $518,240

Grand Total All Awards = $2,052,230

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Physiological Role of Dedifferentiating Dermal Adipose Tissue

Award Number: R01DK131537

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: 12/01/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer