Sunday, June 1, 2025 6/1/2025

Defining the role of an endothelial-adipocyte precursor axis in adipocyte hyperplasia

Award Number: R01DK132563
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Description

Defining the role of an endothelial-adipocyte precursor axis in adipocyte hyperplasia - Project Summary Obesity, which is defined as the excess accumulation of white adipose tissue (WAT) is associated with the development of numerous metabolic, inflammatory, and cardiovascular derangements. However, it is the accumulation of visceral adipose (VWAT) that is associated with metabolic diseases, while the accumulation of subcutaneous adipose (SWAT) is thought to protect against the development of obesity-associated disease. Sex hormones are known to influence both the accumulation of adipose, adipose distribution between VWAT and subcutaneous adipose (SWAT), and the development of metabolic disease, but the precise mechanisms by which sex hormones influence adipose function and distribution remain unclear. We have previously shown that there is an obesity-specific mechanism of adipogenesis that drives adipocyte hyperplasia in a sex-specific pattern. Estrogen plays a role in this process, where exogenous estrogen drives a female-like patterning (both VWAT and SWAT) of adipocyte hyperplasia in male mice, while the absence of systemic estrogen in female mice results in male-like patterning (VWAT only response). Our preliminary data indicates that in the absence of systemic estrogen, estrogen signaling still plays a direct role in VWAT adipocyte hyperplasia at the onset of obesity. We show here that it is VWAT endothelial cells that express aromatase and thereby produce the estrogen required for adipocyte hyperplasia in males and ovariectomized females. We propose that aromatase expression in VWAT endothelium is controlled by glucocorticoids, linking the VWAT-specific actions of estrogen to the hypothalamic-pituitary-adrenal (HPA) axis. Based on our preliminary data, we hypothesize that estrogen and glucocorticoids participate in an endothelial cell-adipocyte precursor axis that regulates obesogenic adipogenesis, thereby influencing distribution of WAT and impacting metabolic disease. Here we will establish the role of adipose- produced estrogen in obesity and metabolic disease, determine the mechanisms that regulate aromatase in VWAT endothelial cells and define the molecular mechanisms of that regulate estrogen action in adipocyte precursors.


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 = $506,520 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	2/27/2025	NON-COMPETING CONTINUATION	$506,520
														Subtotal = $506,520

Issue Date FY: 2024 ( Subtotal = $540,289 )
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/20/2024	NON-COMPETING CONTINUATION	$33,769
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	3/2/2024	NON-COMPETING CONTINUATION	$506,520
														Subtotal = $540,289

Issue Date FY: 2023 ( Subtotal = $562,800 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/21/2023	NEW	$562,800
														Subtotal = $562,800

Grand Total All Awards = $1,609,609

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Defining the role of an endothelial-adipocyte precursor axis in adipocyte hyperplasia

Award Number: R01DK132563

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer