Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany.
Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital Würzburg, Würzburg, Germany.
Front Endocrinol (Lausanne). 2023 May 23;14:1152444. doi: 10.3389/fendo.2023.1152444. eCollection 2023.
Acyl-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/METHODS: Serum 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, mRNA expression was assessed in two CKD mouse models and in two distinct groups of non-CKD mice. Further, mRNA expression of was measured in isolated, differentiated mouse adipocytes - brown and white - after exposure to the uremic agent indoxyl sulfate.
Median [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 mRNA expression in different tissues of CKD mice or in indoxyl sulfate-treated adipocytes .
Circulating 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.
酰基辅酶 A 结合蛋白（ACBP）/地西泮结合抑制剂最近被描述为一种影响食物摄入和脂质代谢的内分泌因子。ACBP 在分解代谢/营养不良状态（如败血症或全身炎症）中失调。然而，迄今为止，在肾功能受损的情况下，尚未对 ACBP 的调节进行研究。
设计/方法：通过酶联免疫吸附试验（ELISA）调查了 60 名慢性血液透析肾衰竭患者（KF）和 60 名肾功能正常的个体的血清 ACBP 浓度，并将其与对照组进行了比较；并在急性肾功能障碍（AKD）的人类模型中进行了研究。此外，在两种 CKD 小鼠模型和两种非 CKD 小鼠的两个不同组中评估了 的 mRNA 表达。进一步，在暴露于尿毒症剂吲哚硫酸后，测量了分离的分化的小鼠脂肪细胞（棕色和白色）中的 mRNA 表达。
与无 KF 组（26.1 [39.1] µg/l）相比，KF 患者（514.0 [339.3] µg/l）的血清 ACBP 中位数[四分位数范围]几乎增加了 20 倍（p<0.001）。在多元分析中，eGFR 是循环 ACBP 的最重要的逆预测因子（标准化β=-0.839；p<0.001）。此外，AKD 使 ACBP 浓度增加了近 3 倍（p<0.001）。在不同 CKD 小鼠组织或吲哚硫酸处理的脂肪细胞中，增加的 ACBP 水平不是由增加的 mRNA 表达引起的。
循环 ACBP 与肾功能呈负相关，这很可能是通过细胞因子在肾脏中的保留引起的。未来的研究需要在与营养不良相关的疾病状态（如 CKD）中研究 ACBP 的生理学，并针对肾功能标志物进行调整。
