Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes
Open accessAbstract
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.
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- Authors
- Kovacova, Z., Tharp, W. G., Liu, D., Wei, W., Xie, H., Collins, S., & Pratley, R. E.
- Affiliations
- Translational Research Institute for Metabolism and Diabetes Florida Hospital Orlando Florida USA
- University of Vermont (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Translational Research Institute for Metabolism and Diabetes (US)
- Corresponding author
- Collins, Sheila
- Pratley, Richard E.
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2016-02-17
- Volume
- 24
- Issue
- 4
- Pages
- 820-828
- ISSN
- 1930-7381 (ISSN-L)
- 1930-739X
- PMC
- PMC5067565
- OpenAlex
- W2276789045
- Cited by
- 85
- References
- 37
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 10 · 2022: 5 · 2021: 9 · 2020: 13 · 2019: 6 · 2018: 7 · 2017: 17 · 2016: 5
- FWCI
- 10.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Obesity (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Research Institute for Dental Sciences, Shahid Beheshti University of Medical Sciences
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- natriuretic peptides, natriuretic peptide receptor A, NPR-C, adipose tissue, skeletal muscle, insulin sensitivity, insulin resistance, type 2 diabetes, impaired glucose tolerance, pioglitazone, thermogenesis, PPARγ coactivator-1α, UCP1
- MeSH terms
- Pioglitazone, Adult, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Insulin Resistance, Male, Middle Aged, Obesity, Receptors, Atrial Natriuretic Factor, Thiazolidinediones
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