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Controlled Clinical Trial
. 2023 Jun 30:14:1195677.
doi: 10.3389/fendo.2023.1195677. eCollection 2023.

Atrial natriuretic peptide and leptin interactions in healthy men

Martin A Daniels  1   2   3   4 , Pamela Fischer-Posovszky  5   6 , Michael Boschmann  7   8 , Reiner Jumpertz-von Schwartzenberg  1   2   3 , Timo D Müller  1   9 , Leontine Sandforth  1   2   3 , Sabine Frank-Podlech  1   2 , Sonja Hülskämper  1   2 , Andreas Peter  1   2   10 , Martin Wabitsch  5   6 , Jens Jordan  11   12 , Andreas L Birkenfeld  1   2   3   13
Affiliations
Controlled Clinical Trial

Atrial natriuretic peptide and leptin interactions in healthy men

Martin A Daniels et al. Front Endocrinol (Lausanne). .

Abstract

Introduction: Atrial natriuretic peptide (ANP), a hormone secreted from the heart, controls cardiovascular and renal functions including arterial blood pressure and natriuresis. ANP also exerts metabolic effects in adipose tissue, liver and skeletal muscle, and interacts with the secretion of adipokines. We tested the hypothesis that ANP lowers concentrations of the anorexigenic adipokine leptin in healthy humans in vivo.

Methods: Human ANP or matching placebo was infused intravenously (iv) into healthy men in a controlled clinical trial.

Results: Within 135 minutes of iv ANP infusion, we observed an acute decrease in plasma leptin levels compared to controls. Free fatty acids markedly increased with ANP infusion in vivo, indicating activated lipolysis. In human SGBS adipocytes, ANP suppressed leptin release.

Discussion: The study shows that the cardiac hormone ANP reduces the levels of the anorexigenic adipokine leptin in healthy humans, providing further support for ANP as a cardiomyokine in a heart - adipose tissue axis. (registered in the German Clinical Trials Register and the WHO International Clinical Trials Registry Platform was granted under DRKS00024559).

Keywords: ANP; atrial natriuretic peptide; heart failure; insulin resistance; leptin; lipolysis; obesity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
ANP reduces plasma leptin levels in healthy men. (A) Plasma leptin levels after acute i.v. infusion of ANP or Placebo. After infusion of ANP over 135 minutes, participants in the treatment group showed a significantly stronger decrease in plasma leptin concentrations than those in the placebo group (B = -0.201, 95% Wald CI [-0.376, -0.026] vs. B = 0.044, 95% Wald CI [-0.097, 0.185] for ANP vs. placebo, respectively; p = 0.024). (B) Plasma leptin levels in relation to ANP concentrations after infusion. Plasma ANP concentration showed a trend to be associated with a decrease in leptin levels in a dose-dependent manner, as shown by an inverse correlation (slope: -0.001nm/pg, Kendall’s Tau-b = -0.367, p = 0.059).
Figure 2
Figure 2
ANP inhibits leptin secretion in human adipocytes. SGBS adipocytes were treated with 10 nM ANP or vehicle in serum-free basal medium. Media supernatants, RNA and protein were harvested after 24, 48, and 72h. (A) The mRNA expression of leptin was assessed by qRT-PCR using the ΔCt method, HPRT was used as reference gene. Mean + SEM of 5 independently performed experiments is shown. (B) Leptin protein expression in cell lysates and media supernatants was determined by Western blot analysis. One representative experiment out of three performed is shown. β-actin was used as loading control. (C, D). Densitometric analysis of Western blot. Mean + SEM of 3 independently performed experiments is shown. *p<0.05.
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