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Mol Metab. 2017 Jan 4;6(3):276-287. doi: 10.1016/j.molmet.2016.12.010. eCollection 2017 Mar.

Divergent effects of a designer natriuretic peptide CD-NP in the regulation of adipose tissue and metabolism.

Author information

1
Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany; Bonn International Graduate School of Drug Sciences BIGSDrugS, University of Bonn, Bonn, Germany.
2
Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany.
3
Cardiorenal Research Laboratory, Department of Cardiovascular Diseases, Mayo Clinic, Rochester, USA.
4
Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany; Bonn International Graduate School of Drug Sciences BIGSDrugS, University of Bonn, Bonn, Germany. Electronic address: alexander.pfeifer@uni-bonn.de.

Abstract

OBJECTIVE:

Obesity is defined as an abnormal increase in white adipose tissue (WAT) and is a major risk factor for type 2 diabetes and cardiovascular disease. Brown adipose tissue (BAT) dissipates energy and correlates with leanness. Natriuretic peptides have been shown to be beneficial for brown adipocyte differentiation and browning of WAT.

METHODS:

Here, we investigated the effects of an optimized designer natriuretic peptide (CD-NP) on murine adipose tissues in vitro and in vivo.

RESULTS:

In murine brown and white adipocytes, CD-NP activated cGMP production, promoted adipogenesis, and increased thermogenic markers. Consequently, mice treated for 10 days with CD-NP exhibited increased "browning" of WAT. To study CD-NP effects on diet-induced obesity (DIO), we delivered CD-NP for 12 weeks. Although CD-NP reduced inflammation in WAT, CD-NP treated DIO mice exhibited a significant increase in body mass, worsened glucose tolerance, and hepatic steatosis. Long-term CD-NP treatment resulted in an increased expression of the NP scavenging receptor (NPR-C) and decreased lipolytic activity.

CONCLUSIONS:

NP effects differed depending on the duration of treatment raising questions about the rational of natriuretic peptide treatment in obese patients.

KEYWORDS:

Adipocytes; Browning; Diet-induced obesity; Natriuretic peptides; cGMP

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