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

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.Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0765-1) contains supplementary material, which is available to authorized users.

Elevated levels of adiponectin associated with major adverse cardiovascular and cerebrovascular events and mortality risk in ischemic stroke

“…Similarity, another study suggested that the apparently positive relationship between adiponectin and risk of CVD and mortality in asymptomatic elderly men might be achieved by elevated NT-pro-BNP [ 49 ]. Furthermore, Masuch et al [ 50 ] found that elevated NT-proBNP might be associated with adiponectin signaling in cardiac healthy individuals. Consistent with those findings, we also found that the predictive value of adiponectin was more pronounced in patients with high levels of NT-pro-BNP (P < 0.001).…”

Metabolomic basis for response to high dose vitamin D in critical illness

“…Analyses were performed on each of the 578 metabolites at day 3 using the R package mediation [15] to obtain bootstrap P values (N ¼ 2000 samples) for the mediation effect of creatinine or bilirubin. Significant mediation was present if the p value was <0.01 and 10% or more of the association was mediated through creatinine or bilirubin levels [16,17].…”

High plasma adiponectin is associated with increased pulmonary blood flow and reduced right ventricular function in patients with pulmonary hypertension

“…Although whether the elevation of adiponectin is the result of increased NT-proBNP or as an active contributor to worsening heart failure progression remains unclear, some findings suggested that the effects of NT-proBNP might relate to adiponectin signaling [33]. As demonstrated by Masuch A et al, the effect of NT-proBNP on lipid prolife was partially mediated by adiponectin [33]. By using the mediation effect model, we also found a mediation effect of adiponectin on the association of NT-proBNP and right ventricular function.…”