Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes

Obesity (Silver Spring). 2016 Apr;24(4):820-8. doi: 10.1002/oby.21418. Epub 2016 Feb 17.


Objective: Cardiac natriuretic peptides (NPs) bind to two receptors (NPRA-mediator of signaling; NPRC-clearance receptor) whose ratio, NPRR (NPRA/NPRC), determines the NP bioactivity. This study investigated the relationship of NP receptor gene expression in adipose tissue and muscle with obesity and glucose intolerance. Prospectively, the study also assessed whether changes in NP receptor expression and thermogenic gene markers accompanied improvements of insulin sensitivity.

Methods: A cross-sectional study of subjects with a wide range of BMI and glucose tolerance (n = 50) was conducted, as well as a randomized 12-week trial of subjects with type 2 diabetes mellitus (T2DM) treated with pioglitazone (n = 9) or placebo (n = 10).

Results: NPRR mRNA was significantly lower in adipose tissue of subjects with obesity when compared with lean subjects (P ≤ 0.001). NPRR decreased with progression from normal glucose tolerance to T2DM (P < 0.01) independently of obesity. Treatment of subjects with T2DM with pioglitazone increased NPRR in adipose tissue (P ≤ 0.01) in conjunction with improvements in insulin sensitivity and increases of the thermogenic markers PPARγ coactivator-1α and uncoupling protein 1 (P ≤ 0.01).

Conclusions: Decreased adipose tissue NPRR was associated with obesity, glucose intolerance, and insulin resistance. This relationship was not observed for skeletal muscle NPRR. Pharmacological improvement of insulin sensitivity in subjects with T2DM was tied to improvement in NPRR and increased expression of genes involved in thermogenic processes.

Trial registration: NCT00656864.

Keywords: adipose tissue; natriuretic peptide receptors; obesity; type 2 diabetes mellitus.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / metabolism
  • Diabetes Mellitus, Type 2* / physiopathology
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin Resistance / physiology*
  • Male
  • Middle Aged
  • Obesity* / metabolism
  • Obesity* / physiopathology
  • Pioglitazone
  • Receptors, Atrial Natriuretic Factor* / analysis
  • Receptors, Atrial Natriuretic Factor* / metabolism
  • Thiazolidinediones / therapeutic use


  • Hypoglycemic Agents
  • Thiazolidinediones
  • Receptors, Atrial Natriuretic Factor
  • Pioglitazone

Associated data