Roux-en-Y胃旁路术而非袖状胃切除术可降低病态肥胖患者的血浆前蛋白转化酶枯草溶菌素9（PCSK9）水平。

Roux-en-Y gastric bypass, but not sleeve gastrectomy, decreases plasma PCSK9 levels in morbidly obese patients.

作者信息

Blanchard C, Ledoux S, Verhaegen A, Wargny M, Letessier E, Stepanian A, Huten N, Jacobi D, Krempf M, Le Bras M, Perrocheau Guillouche M, Arnaud L, Pichelin M, Van Gaal L, Cariou B, Le May C

机构信息

University of Nantes, CNRS, Inserm, Thorax Institute, 44000 Nantes, France; Clinical Department of Digestive and Endocrine Surgery, CHU of Nantes, Nantes, France.

Department of Functional Explorations, North Francilien Integrated Obesity Centre (CINFO), Hôpital Louis Mourier (AP-HP.7), University of Paris, Paris, France.

出版信息

Diabetes Metab. 2020 Nov;46(6):480-487. doi: 10.1016/j.diabet.2020.01.003. Epub 2020 Feb 4.

DOI:10.1016/j.diabet.2020.01.003

PMID:32032671

Abstract

AIM

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a master regulator of low-density lipoprotein cholesterol (LDL-C) metabolism, acting as an endogenous inhibitor of the LDL receptor. While it has been shown that bariatric surgery differentially affects plasma LDL-C levels, little is known of its effects on plasma PCSK9 concentrations. Therefore, the present study aimed to: (i) investigate the effect of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on plasma PCSK9 concentrations; and (ii) correlate baseline or postoperative plasma PCSK9 concentration variations with anthropometric and metabolic parameters.

METHODS

Fasting plasma PCSK9 levels were measured by ELISA in morbidly obese patients before and 6 months after bariatric surgery. Patients were recruited from three prospective cohorts (in Nantes and Colombes in France, and Antwerp in Belgium).

RESULTS

A total of 156 patients (34SG, 122RYGB) were included. Plasma PCSK9, LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) levels were significantly reduced after RYGB (-19.6%, -16.6% and -19.5%, respectively; P<0.0001), but not after SG. In all patients, postoperative PCSK9 change was positively correlated with fasting plasma glucose (FPG; r=0.22, P=0.007), HOMA-IR (r=0.24, P=0.005), total cholesterol (r=0.17, P=0.037) and non-HDL-C (r=0.17, P=0.038) variations, but not LDL-C. In contrast to what was observed for glucose parameters (FPG, HOMA-IR), correlation between PCSK9 and non-HDL-C changes after RYGB was independent of total weight loss.

CONCLUSION

RYGB, but not SG, promotes a significant reduction in plasma PCSK9 levels, and such changes in circulating PCSK9 levels after RYGB appear to be more associated with glucose improvement than with lipid homoeostasis parameters.

摘要

目的

前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）是低密度脂蛋白胆固醇（LDL-C）代谢的主要调节因子，作为LDL受体的内源性抑制剂。虽然已有研究表明减肥手术对血浆LDL-C水平有不同影响，但对其对血浆PCSK9浓度的影响知之甚少。因此，本研究旨在：（i）研究袖状胃切除术（SG）和Roux-en-Y胃旁路术（RYGB）对血浆PCSK9浓度的影响；（ii）将基线或术后血浆PCSK9浓度变化与人体测量和代谢参数相关联。

方法

通过酶联免疫吸附测定法（ELISA）测量肥胖患者在减肥手术前及术后6个月的空腹血浆PCSK9水平。患者来自三个前瞻性队列（法国的南特和科隆布以及比利时的安特卫普）。

结果

共纳入156例患者（34例行SG，122例行RYGB）。RYGB术后血浆PCSK9、LDL-C和非高密度脂蛋白胆固醇（non-HDL-C）水平显著降低（分别降低-19.6%、-16.6%和-19.5%；P<0.0001），但SG术后未降低。在所有患者中，术后PCSK9变化与空腹血糖（FPG；r=0.22，P=0.007）、稳态模型评估胰岛素抵抗指数（HOMA-IR；r=0.24，P=0.005）、总胆固醇（r=0.17，P=0.037）和non-HDL-C（r=0.17，P=0.038）变化呈正相关，但与LDL-C无关。与血糖参数（FPG、HOMA-IR）的观察结果相反，RYGB术后PCSK9与non-HDL-C变化之间的相关性与总体重减轻无关。