Dataset Information

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

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.

SUBMITTER: Glode A

PROVIDER: S-EPMC5323888 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Glöde Anja A Naumann Jennifer J Gnad Thorsten T Cannone Valentina V Kilic Ana A Burnett John C JC Pfeifer Alexander A

Molecular metabolism 20170104 3

<h4>Objective</h4>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.<h4>Methods</h4>Here, we investigated the effects of an optimized designer natriuretic peptide (CD-NP) on murine adipose tissues <i>in vitro</i> and ...[more]

PMID: 28271034

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Project description:OBJECTIVES:The goal of this study was to investigate the association between natriuretic peptides and body fat distribution in a multiethnic cohort. BACKGROUND:Natriuretic peptides stimulate lipolysis, reduce weight gain, and promote adipocyte browning in animal models, but data are lacking in humans. METHODS:A total of 2,619 participants without heart failure in the Dallas Heart Study underwent measurements of 1) B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP); and 2) body fat distribution by dual energy x-ray absorptiometry and magnetic resonance imaging. Cross-sectional associations of natriuretic peptides with adiposity phenotypes were examined after adjustment for age, sex, race, comorbidities, and body mass index. RESULTS:Median BNP and NT-proBNP levels in the study cohort (mean age 44 years; 56% women, 48% African Americans, 32% obese) were 3.0 and 28.1 pg/ml, respectively. Natriuretic peptide levels above the median were associated with a more favorable body fat profile and less insulin resistance, including lower visceral fat, liver fat, and homeostasis model assessment of insulin resistance index, and increased lower body fat and higher adiponectin (p < 0.05 for each). In multivariable analyses, NT-proBNP remained inversely associated with visceral fat (beta coefficient = -0.08; p < 0.0001) and liver fat (beta coefficient = -0.14; p < 0.0001) and positively associated with lower body fat (beta coefficient = 0.07; p < 0.0001) independent of age, sex, race, and obesity status; findings were similar with BNP. Adjustment for body composition, homeostasis model assessment of insulin resistance index, circulating androgens, and adipocytokines did not attenuate the associations. CONCLUSIONS:Higher natriuretic peptide levels were independently associated with a favorable adiposity profile, characterized by decreased visceral and liver fat and increased lower body fat, suggesting a link between the heart and adipose tissue distribution mediated through natriuretic peptides.

Dataset Information

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

Publications

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

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