Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Natriuretic peptide and cGMP signaling in adipose tissue and energy metabolism

Award Number: R01DK126890
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: 04/15/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

Group Awards By:

View Award Description

Natriuretic peptide and cGMP signaling in adipose tissue and energy metabolism - PROJECT SUMMARY The epidemic of cardiometabolic disease occurring throughout the world is taking a heavy toll on individuals’ quality of life, along with a huge economic impact Excess caloric intake leading to obesity is a major driver of the cardiometabolic syndrome. Brown adipose tissue (BAT) evolved in homeotherms as a mean to maintain body temperature by generating heat from stored calories. Brown adipocytes are highly enriched in mitochondria and express a unique protein called uncoupling protein-1 (UCP1). UCP1 ‘uncouples’ the mitochondrial proton gradient from ATP production, thus avidly consuming glucose and fatty acids with the result being net energy expenditure. Active brown fat is present in adult humans and its amount is significantly correlated with reduced body fat and circulating triglycerides, greater insulin sensitivity, and lowered incidence of Type II diabetes. Increasing brown adipocyte amount and activity could reduce the risk of cardiometabolic disease. The sympathetic nervous system (SNS)-derived catecholamine norepinephrine, which act through β-adrenergic receptors and cAMP, is a well-established activator of BAT and the recruitment of UCP1-positive cells in white adipose tissue (WAT) depots (a process termed ‘browning’ or ‘beiging’). We have shown in prior work that the cardiac hormones atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) also stimulate a similar ‘browning’ program in mouse and human adipocytes, and protect against obesity-associated insulin resistance, hepatic steatosis and inflammation. This suggests that increasing NP signaling in adipose tissues is metabolically beneficial. NP activation of NP receptor A (NPRA) leads to cGMP production, while the NP ‘clearance receptor’ NPRC removes NPs from circulation, and the ratio of NPRA to NPRC determines NP signaling capacity. Clinical studies show that compared to lean individuals, obese individuals have lower circulating NP level, increased NPRC level in adipose tissue, and blunted lipolytic responses to NPs. We observed similar patterns of receptor expression and physiological responses in mice. It has been postulated that higher adipose NPRC levels increases NP clearance, thus reducing NP availability in the circulation and efficacy in target tissues, resulting in a so-called ‘natriuretic handicap’. On the other hand, conditions such as fasting and cold temperature exposure reduce the level of NPRC expression, resulting in an increased NPRA/NPRC ratio and thus NP/cGMP signaling. Our studies with mouse models further support these observations. We also find that the expression of other components of the NP signaling system, such as phosphodiesterase-9 and the peptidase neprilysin are also decreased in response to cold and βAR agonists The overall objective of this project is to: define the transcriptional regulatory mechanisms of the Nprc, Pde9 and Mme genes in human and mouse adipocytes; determine whether increased levels of NPRC in obesity serves as a ‘sink’ to remove NPs from circulation, thus creating the ‘natriuretic handicap’, and test the effects of selective NP ligands to modulate insulin sensitivity.


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	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	12/14/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $494,468 )
2025	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	4/1/2025	NON-COMPETING CONTINUATION	$445,022
2025	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	5/28/2025	NON-COMPETING CONTINUATION	$49,446
														Subtotal = $494,468

Issue Date FY: 2024 ( Subtotal = $474,690 )
2024	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	5/20/2024	NON-COMPETING CONTINUATION	$29,668
2024	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	3/4/2024	NON-COMPETING CONTINUATION	$445,022
														Subtotal = $474,690

Issue Date FY: 2023 ( Subtotal = $500,295 )
2023	2023	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/28/2023	NON-COMPETING CONTINUATION	$500,295
														Subtotal = $500,295

Issue Date FY: 2022 ( Subtotal = $506,890 )
2022	2022	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/14/2022	NEW	$506,890
														Subtotal = $506,890

Grand Total All Awards = $1,976,343

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Natriuretic peptide and cGMP signaling in adipose tissue and energy metabolism

Award Number: R01DK126890

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: 04/15/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer