Skip to main content
Journal cover image

Pharmacologic blockade of the natriuretic peptide clearance receptor promotes weight loss and enhances insulin sensitivity in type 2 diabetes.

Publication ,  Journal Article
Wang, L; Tang, Y; Herman, MA; Spurney, RF
Published in: Transl Res
May 2023

While natriuretic peptides (NPs) are primarily known for their renal and cardiovascular actions, NPs stimulate lipolysis in adipocytes and induce a thermogenic program in white adipose tissue (WAT) that resembles brown fat. The biologic effects of NPs are negatively regulated by the NP clearance receptor (NPRC), which binds and degrades NPs. Knockout (KO) of NPRC protects against diet induced obesity and improves insulin sensitivity in obese mice. To determine if pharmacologic blockade of NPRC enhanced the beneficial metabolic actions of NPs in type 2 diabetes, we blocked NP clearance in a mouse model of type 2 diabetes using the specific NPRC ligand ANP(4-23). We found that treatment with ANP(4-23) caused a significant decrease in body weight by increasing energy expenditure and reducing fat mass without a change in lean body mass. The decrease in fat mass was associated with a significant improvement in insulin sensitivity and reduced serum insulin levels. These beneficial effects were accompanied by a decrease in infiltrating macrophages in adipose tissue, and reduced expression of inflammatory markers in both serum and WAT. These data suggest that inhibiting NP clearance may be an effective pharmacologic approach to promote weight loss and enhance insulin sensitivity in type 2 diabetes. Optimizing the therapeutic approach may lead to useful therapies for obesity and type 2 diabetes.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Transl Res

DOI

EISSN

1878-1810

Publication Date

May 2023

Volume

255

Start / End Page

140 / 151

Location

United States

Related Subject Headings

  • Weight Loss
  • Obesity
  • Natriuretic Peptides
  • Mice, Knockout
  • Mice
  • Insulin Resistance
  • General Clinical Medicine
  • Diabetes Mellitus, Type 2
  • Animals
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, L., Tang, Y., Herman, M. A., & Spurney, R. F. (2023). Pharmacologic blockade of the natriuretic peptide clearance receptor promotes weight loss and enhances insulin sensitivity in type 2 diabetes. Transl Res, 255, 140–151. https://doi.org/10.1016/j.trsl.2022.12.005
Wang, Liming, Yuping Tang, Mark A. Herman, and Robert F. Spurney. “Pharmacologic blockade of the natriuretic peptide clearance receptor promotes weight loss and enhances insulin sensitivity in type 2 diabetes.Transl Res 255 (May 2023): 140–51. https://doi.org/10.1016/j.trsl.2022.12.005.
Wang, Liming, et al. “Pharmacologic blockade of the natriuretic peptide clearance receptor promotes weight loss and enhances insulin sensitivity in type 2 diabetes.Transl Res, vol. 255, May 2023, pp. 140–51. Pubmed, doi:10.1016/j.trsl.2022.12.005.
Journal cover image

Published In

Transl Res

DOI

EISSN

1878-1810

Publication Date

May 2023

Volume

255

Start / End Page

140 / 151

Location

United States

Related Subject Headings

  • Weight Loss
  • Obesity
  • Natriuretic Peptides
  • Mice, Knockout
  • Mice
  • Insulin Resistance
  • General Clinical Medicine
  • Diabetes Mellitus, Type 2
  • Animals
  • 3202 Clinical sciences