B-type natriuretic peptide modulates ghrelin, hunger, and satiety in healthy men

Abstract

Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from ventricular cardiomyocytes. The pathophysiological mechanisms linking heart failure and appetite regulation remain unknown. In this study, we investigated the impact of intravenous BNP administration on appetite-regulating hormones and subjective ratings of hunger and satiety in 10 healthy volunteers. Participants received in a randomized, placebo-controlled, crossover, single-blinded study (subject) placebo once and 3.0 pmol/kg/min human BNP-32 once administered as a continuous infusion during 4 h. Circulating concentrations of appetite-regulating peptides were measured hourly. Subjective ratings of hunger and satiety were evaluated by visual analog scales. BNP inhibited the fasting-induced increase in total and acylated ghrelin concentrations over time (P = 0.043 and P = 0.038, respectively). In addition, BNP decreased the subjective rating of hunger (P = 0.009) and increased the feeling of satiety (P = 0.012) when compared with placebo. There were no significant changes in circulating peptide YY, glucagon-like peptide 1, oxyntomodulin, pancreatic polypeptide, leptin, and adiponectin concentrations. In summary, our results demonstrate that BNP exerts anorectic effects and reduces ghrelin concentrations in men. These data, taken together with the known cardiovascular properties of ghrelin, support the existence of a heart-gut-brain axis, which could be therapeutically targeted in patients with heart failure and obesity.

Trial registration: ClinicalTrials.gov NCT01375153.

Figures

FIG. 1.

Changes in circulating BNP concentrations. BNP administered as a continuous intravenous infusion of 3 pmol/kg/min. Horizontal black bar shows infusion duration. Data are presented as mean ± SEM. ●, 3 pmol/kg/min BNP; ○, placebo; *P < 0.05.

FIG. 2.

Effects of BNP on acylated and total ghrelin concentrations. A: Profile of changes in plasma ghrelin concentrations. B: Differences between ghrelin concentrations at baseline and time point 4 h. C: Profile of changes in acylated ghrelin concentrations. D: Differences between acylated ghrelin concentrations at baseline and at time point 4 h. Data are presented as mean ± SEM. Horizontal black bar shows infusion duration. ●, 3 pmol/kg/min BNP; ○, placebo; *P < 0.05.

FIG. 3.

Effects of BNP on gut peptides and adipokines. BNP-induced changes in circulating PYY3–36 (A), GLP-1 (B), oxyntomodulin (C), PP (D), leptin (E), and adiponectin concentrations (F). Data are presented as mean ± SEM. Horizontal black bar shows infusion duration. ●, 3 pmol/kg/min BNP; ○, placebo.

FIG. 4.

Effects of BNP on subjective ratings of hunger and satiety, as measured by VAS. Scores are depicted as change from the 0 value (mm). A: Profile of hunger VAS values. B: Differences between hunger VAS values at baseline and time point 4 h. C: Profile of satiety VAS values. D: Differences between satiety VAS values at baseline and time point 4 h. Data are presented as mean ± SEM. Horizontal black bar shows infusion duration. ●, 3 pmol/kg/min BNP; ○, placebo; *P < 0.05.