Metabolomic profiling implicates adiponectin as mediator of a favorable lipoprotein profile associated with NT-proBNP

Annette Masuch,Martin Bahls,Gabi Kastenmüller,Anna Artati,Marcus Dörr,Kathrin Budde,Henry Völzke,Jerzy Adamski,Stephan B Felix,Nele Friedrich,Stephanie Zylla,Matthias Nauck,Maik Pietzner

doi:10.1186/s12933-018-0765-1

Abstract

BackgroundThe N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is an important biomarker for the diagnosis of heart failure. Apart from this and only recently recognized, NT-proBNP levels associate with higher HDL- and lower LDL-cholesterol levels comprising a favorable blood lipid profile. To further examine this observation, the lipoprotein profile in relation to NT-proBNP was examined in-depth by proton nuclear magnetic resonance spectroscopy (1H-NMR). We complemented this investigation with a state-of-the-art untargeted metabolomics approach.MethodsLipoprotein particles were determined by 1H-NMR spectroscopy in 872 subjects without self-reported diabetes from the population-based Study of Health in Pomerania (SHIP)-TREND with available NT-proBNP measurements. Comprehensive metabolomics data for plasma and urine samples were obtained. Linear regression models were performed to assess the associations between serum concentrations of NT-proBNP and the metabolites/lipoprotein particles measured in plasma or urine.ResultsAn increase in serum NT-proBNP was associated with a benefical lipoprotein profile, including a decrease in VLDL, IDL and LDL-particles along with an increase in large HDL particles. These findings were replicated in a second independent cohort. Serum concentrations of NT-proBNP showed significant inverse associations with seven plasma metabolites while associations with 39 urinary metabolites, mostly comprising amino acids and related intermediates, were identified. Mediation analyses revealed adiponection as mediating factor for the associations observed with lipoproteins particles.ConclusionsMost of the metabolic changes associated with NT-proBNP implicate significant influence on the blood lipid profile besides vasodilatory and the diuretic action of BNP signaling. Our data suggest that the more favorable lipoprotein profile as associated with elevated NT-proBNP concentrations in mainly cardiac healthy individuals might relate to adiponectin signaling indicating even indirect cardio-protective effects for NT-proBNP.

Highlights

The N-terminal fragment of the prohormone of brain natriuretic peptide (NT-proBNP) plays a central role as a biomarker in the diagnosis of heart failure (HF), a syndrome resulting in reduced cardiac output and/ or elevated intracardiac pressure at rest or during stress [1]
A recent study further revealed that BNP within the reference range (< 100 ng/L) was inversely correlated with total cholesterol, non-high-density lipoprotein (HDL) cholesterol, and non-fasting triglycerides representing a favorable lipoprotein profile confirming an observation from a number of previous studies [11,12,13]
In order to improve the understanding of NTproBNP beyond cardiac dysfunction and to explore the relation to lipoprotein metabolism, the present study aimed to examine the associations of NT-proBNP plasma concentrations with the metabolic profile of a large population

Summary

Introduction

The N-terminal fragment of the prohormone of brain natriuretic peptide (NT-proBNP) plays a central role as a biomarker in the diagnosis of heart failure (HF), a syndrome resulting in reduced cardiac output and/ or elevated intracardiac pressure at rest or during stress [1]. In line with the assumption of an interrelation between body fat and the natriuretic hormone system, higher BNP levels within the reference range were associated with a favorable distribution of adipose tissue meaning lower visceral and liver fat and increased lower-body fat in participants of the DALLAS Heart Study [8]. The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is an important biomarker for the diagnosis of heart failure Apart from this and only recently recognized, NT-proBNP levels associate with higher HDLand lower LDL-cholesterol levels comprising a favorable blood lipid profile. To further examine this observation, the lipoprotein profile in relation to NT-proBNP was examined in-depth by proton nuclear magnetic resonance spectroscopy (1H-NMR). Linear regression models were performed to assess the associations between serum concentrations of NT-proBNP and the metabolites/lipoprotein particles measured in plasma or urine

Methods

Results

Discussion

Conclusion