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严重肥胖症患者接受减重手术后,血清颗粒蛋白聚糖水平和基因表达在皮下与内脏脂肪组织中的比较。

Progranulin serum levels and gene expression in subcutaneous vs visceral adipose tissue of severely obese patients undergoing bariatric surgery.

机构信息

Department of Internal Medicine III, Justus Liebig University of Giessen, Giessen, Germany.

Comprehensive Biobank Marburg (CBBMR), Philipps University of Marburg, Marburg, Germany.

出版信息

Clin Endocrinol (Oxf). 2019 Sep;91(3):400-410. doi: 10.1111/cen.14040. Epub 2019 Jun 7.

Abstract

BACKGROUND

Progranulin represents an adipokine putatively mediating insulin resistance and inflammation. Data in humans are sparse, and the source of circulating progranulin in obesity is unknown.

OBJECTIVES

Serum progranulin concentrations and subcutaneous (sc) as well as visceral (vis) adipose tissue (AT) progranulin expression were quantified in a large cohort of patients with obesity undergoing bariatric surgery (BS) (n = 153) or a low-calorie diet (LCD) (n = 121).

COHORTS AND METHODS

Paired serum and AT mRNA samples were obtained from patients with severe obesity undergoing BS (ROBS cohort; Research in Obesity and Bariatric Surgery). Serum progranulin was measured by ELISA in both cohorts, and AT mRNA expression was analysed by quantitative real-time PCR in bariatric patients.

RESULTS

There was no gender-specific effect in serum progranulin or AT progranulin expression. Importantly, circulating progranulin was independent from adipose tissue gene expression in paired samples. sc AT progranulin expression was higher than in vis AT (P = 0.027), and there was a positive correlation between sc AT and vis AT gene expression (P < 0.001; r = +0.34). Serum progranulin strongly and rapidly increased after BS within 3 days and remained elevated up to 12 months. Serum progranulin was strongly correlated with serum CTRP-3 levels.

CONCLUSIONS

The present study provides detailed progranulin gene expression data in sc and vis AT in a large, prospective and observational cohort of patients with severe obesity. Serum progranulin concentrations are not predicted by sc or vis AT progranulin gene expression. Thus, AT seems not to be the main source of circulating progranulin levels in obesity.

摘要

背景

颗粒蛋白前体代表一种脂肪因子,推测它介导胰岛素抵抗和炎症。人体数据稀少,肥胖症患者循环颗粒蛋白前体的来源尚不清楚。

目的

在接受减肥手术(BS)或低热量饮食(LCD)的肥胖患者中,定量检测大量肥胖患者的血清颗粒蛋白前体浓度以及皮下(sc)和内脏(vis)脂肪组织(AT)的颗粒蛋白前体表达。

队列和方法

从接受减肥手术的严重肥胖患者(ROBS 队列;肥胖与减肥手术研究)中获得配对的血清和 AT mRNA 样本。在两个队列中均通过 ELISA 检测血清颗粒蛋白前体,在减肥患者中通过定量实时 PCR 分析 AT mRNA 表达。

结果

血清颗粒蛋白前体或 AT 颗粒蛋白前体表达没有性别特异性影响。重要的是,循环颗粒蛋白前体与配对样本中的脂肪组织基因表达无关。sc AT 的颗粒蛋白前体表达高于 vis AT(P=0.027),并且 sc AT 和 vis AT 基因表达之间存在正相关(P<0.001;r=+0.34)。BS 后,血清颗粒蛋白前体在 3 天内迅速升高,持续升高 12 个月。血清颗粒蛋白前体与血清 CTRP-3 水平强烈相关。

结论

本研究提供了在严重肥胖患者的大型、前瞻性和观察性队列中,sc 和 vis AT 中颗粒蛋白前体基因表达的详细数据。血清颗粒蛋白前体浓度不能通过 sc 或 vis AT 颗粒蛋白前体基因表达预测。因此,AT 似乎不是肥胖症患者循环颗粒蛋白前体水平的主要来源。

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