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心力衰竭患者与健康对照者脂肪组织中 B 型利钠肽 1-32 的脂肪分解作用比较。

Lipolytic effects of B-type natriuretic peptide 1-32 in adipose tissue of heart failure patients compared with healthy controls.

机构信息

Department of Cardiology, Institute of Clinical and Experimental Medicine, IKEM, Videnska 1958/9, Prague, Czech Republic.

出版信息

J Am Coll Cardiol. 2011 Sep 6;58(11):1119-25. doi: 10.1016/j.jacc.2011.05.042.

Abstract

OBJECTIVES

Our goal was to examine the role of B-type natriuretic peptide (BNP) in lipolysis regulation in heart failure (HF) patients.

BACKGROUND

Enhanced adipose tissue lipolysis can contribute to myocardial lipid overload, insulin resistance, and cachexia in advanced HF. Natriuretic peptides were recently recognized to stimulate lipolysis in healthy subjects.

METHODS

Ten nondiabetic HF patients (New York Heart Association functional class III, 50% nonischemic etiology) and 13 healthy subjects (control subjects) of similar age, sex, and body composition underwent a microdialysis study of subcutaneous abdominal adipose tissue. Four microdialysis probes were simultaneously perfused with 0.1 μM BNP(1-32,) 10 μM BNP(1-32), 10 μM norepinephrine (NE) or Ringer's solution. Outgoing dialysate glycerol concentration (DGC) was measured as an index of lipolysis.

RESULTS

Spontaneous lipolysis was higher in HF patients compared with control subjects (DGC: 189 ± 37 μmol/l vs. 152 ± 35 μmol/l, p < 0.01). Response to NE was similar (p = 0.35) in HF patients and control subjects (DGC increase of 1.7 ± 0.2-fold vs. 1.7 ± 0.4-fold). BNP(1-32) 10 μM markedly increased lipolysis in both HF patients and control subjects (DGC increase of 2.8 ± 0.5-fold vs. 3.2 ± 0.3-fold), whereas the response to 0.1 μM BNP(1-32) was more pronounced in HF patients (p = 0.02). In HF patients, spontaneous lipolysis positively correlated with insulin resistance and the response to BNP(1-32) negatively correlated with adiposity.

CONCLUSIONS

BNP(1-32) exerts strong lipolytic effects in humans. Despite marked elevation of plasma immunoreactive BNP, the responsiveness of adipose tissue to BNP(1-32) is not attenuated in HF, possibly reflecting a deficiency of endogenous bioactive BNP. Lipolytic effects of BNP can contribute to excessive fatty acid mobilization in advanced HF.

摘要

目的

我们的目标是研究 B 型利钠肽(BNP)在心力衰竭(HF)患者脂肪分解调节中的作用。

背景

增强脂肪组织的脂肪分解会导致心肌脂质过载、胰岛素抵抗和晚期 HF 的恶病质。利钠肽最近被认为可以刺激健康受试者的脂肪分解。

方法

10 名非糖尿病 HF 患者(纽约心脏协会功能分级 III 级,50%为非缺血性病因)和 13 名年龄、性别和身体成分相似的健康受试者(对照组)接受腹部皮下脂肪组织的微透析研究。四个微透析探头同时用 0.1μM BNP(1-32)、10μM BNP(1-32)、10μM 去甲肾上腺素(NE)或林格氏液进行灌流。作为脂肪分解指标的流出液甘油浓度(DGC)进行测量。

结果

与对照组相比,HF 患者的自发性脂肪分解更高(DGC:189±37μmol/l 与 152±35μmol/l,p<0.01)。HF 患者和对照组对 NE 的反应相似(p=0.35)(DGC 增加 1.7±0.2 倍与 1.7±0.4 倍)。10μM BNP(1-32)显著增加了 HF 患者和对照组的脂肪分解(DGC 增加 2.8±0.5 倍与 3.2±0.3 倍),而 0.1μM BNP(1-32)在 HF 患者中的反应更为明显(p=0.02)。在 HF 患者中,自发性脂肪分解与胰岛素抵抗呈正相关,而对 BNP(1-32)的反应与肥胖呈负相关。

结论

BNP(1-32)在人体中具有强烈的脂肪分解作用。尽管血浆免疫反应性 BNP 明显升高,但 HF 患者对 BNP(1-32)的反应性并未减弱,这可能反映了内源性生物活性 BNP 的缺乏。BNP 的脂肪分解作用可能导致晚期 HF 中脂肪酸的过度动员。

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