TY - JOUR
T1 - Divergent effects of a designer natriuretic peptide CD-NP in the regulation of adipose tissue and metabolism
AU - Glöde, Anja
AU - Naumann, Jennifer
AU - Gnad, Thorsten
AU - Cannone, Valentina
AU - Kilic, Ana
AU - Burnett, John C.
AU - Pfeifer, Alexander
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - Adipocytes
KW - Browning
KW - Diet-induced obesity
KW - Natriuretic peptides
KW - cGMP
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U2 - 10.1016/j.molmet.2016.12.010
DO - 10.1016/j.molmet.2016.12.010
M3 - Article
C2 - 28271034
AN - SCOPUS:85009433301
SN - 2212-8778
VL - 6
SP - 276
EP - 287
JO - Molecular Metabolism
JF - Molecular Metabolism
IS - 3
ER -