Renal function is a major predictor of circulating acyl-CoA-binding protein/diazepam-binding inhibitor

Abstract

ObjectiveAcyl-CoA-binding protein (ACBP)/diazepam-binding inhibitor has lately been described as an endocrine factor affecting food intake and lipid metabolism. ACBP is dysregulated in catabolic/malnutrition states like sepsis or systemic inflammation. However, regulation of ACBP has not been investigated in conditions with impaired kidney function, so far.Design/methodsSerum ACBP concentrations were investigated by enzyme-linked immunosorbent assay i) in a cohort of 60 individuals with kidney failure (KF) on chronic haemodialysis and compared to 60 individuals with a preserved kidney function; and ii) in a human model of acute kidney dysfunction (AKD). In addition, mACBP mRNA expression was assessed in two CKD mouse models and in two distinct groups of non-CKD mice. Further, mRNA expression of mACBP was measured in vitro in isolated, differentiated mouse adipocytes - brown and white - after exposure to the uremic agent indoxyl sulfate.ResultsMedian [interquartile range] serum ACBP was almost 20-fold increased in KF (514.0 [339.3] µg/l) compared to subjects without KF (26.1 [39.1] µg/l) (p<0.001). eGFR was the most important, inverse predictor of circulating ACBP in multivariate analysis (standardized β=-0.839; p<0.001). Furthermore, AKD increased ACBP concentrations almost 3-fold (p<0.001). Increased ACBP levels were not caused by augmented mACBP mRNA expression in different tissues of CKD mice in vivo or in indoxyl sulfate-treated adipocytes in vitro.ConclusionsCirculating ACBP inversely associates with renal function, most likely through renal retention of the cytokine. Future studies need to investigate ACBP physiology in malnutrition-related disease states, such as CKD, and to adjust for markers of renal function.

Circulating acyl-CoA-binding protein/diazepam-binding inhibitor in gestational diabetes mellitus

“…In addition, ACBP levels positively and independently correlate with creatinine concentrations in the post-partum cohort, suggesting increased ACBP levels with impaired renal function. This is in accordance with a recent study from us demonstrating significantly increased ACBP concentrations in patients with kidney failure and acute kidney dysfunction [ 14 ].…”

“…In human studies, ACBP has also demonstrated a positive correlation with BMI, providing further support for its role as an obesogenic factor [ 9 , 12 , 13 ]. Lately, we could establish markedly increased ACBP levels in kidney failure (KF) and furthermore confirm results of different studies on ACBP´s independent association with dyslipidemia [ 12 – 14 ]. In addition, Montegut et al associated high plasma concentrations of ACBP with an elevated risk of future cardiovascular disease [ 13 ].…”

“…In line with this, in non-pregnant human cohorts, ACBP has been associated with elevated insulin levels in obese individuals, while starved mice injected with anti-ACBP antibodies exhibited a decrease in plasma insulin [ 9 ]. Moreover, it is known, that ACBP is linked to an adverse, insulin-resistance favoring lipid profile with increased TG and decreased HDL cholesterol [ 12 – 14 ]. Hence, the pathophysiological connection between ACBP and insulin resistance may lead to enhanced insulin secretion of beta cells in order to overcome this insulin resistant state.…”