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肥胖患者的脂肪组织重塑是导致脂肪肝存在和严重程度的决定因素。

Adipose tissue remodelling in obese subjects is a determinant of presence and severity of fatty liver disease.

机构信息

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.

出版信息

Diabetes Metab Res Rev. 2021 Jan;37(1):e3358. doi: 10.1002/dmrr.3358. Epub 2020 Jul 1.

Abstract

AIMS

Experimental data suggest that visceral adipose tissue (VAT) dysfunction contributes to non-alcoholic fatty liver disease (NAFLD) development in obesity, however, data on humans are limited. Aims of this study were to investigate the relationship between NAFLD and VAT morphofunctional impairment and to determine whether the extent of VAT remodelling is associated with liver damage and metabolic alterations in obesity.

METHODS

We analysed data from 40 obese individuals candidate to bariatric surgery in whom paired intraoperative liver and omental biopsies were performed for diagnosing NAFLD and VAT inflammation by immunohistochemistry and mRNA expression studies.

RESULTS

Within our study population, NAFLD was significantly associated with greater VAT CD68 macrophages infiltration (P = .04), fibrosis (P = .04) and impaired microvascular density (P = .03) as well as increased expression of markers of local hypoxia, apoptosis and inflammation (UNC5B, CASP7, HIF1-α, IL-8, MIP2, WISP-1, all P < .01). The degree of VAT inflammation correlated with the severity of hepatic injury (steatosis, inflammation, fibrosis; all P < .01) and impaired gluco-metabolic profile.

CONCLUSIONS

In obese patients, NAFLD is associated in a dose-dependent manner with signs of VAT remodelling, which reflect more severe clinical metabolic impairment. Our study depicts morphological alterations and novel mediators of VAT dysfunction, adding knowledge for future therapeutic approaches to NAFLD and its metabolic complications.

摘要

目的

实验数据表明,内脏脂肪组织(VAT)功能障碍在肥胖症中非酒精性脂肪性肝病(NAFLD)的发展中起作用,然而,人类的数据有限。本研究的目的是探讨 NAFLD 与 VAT 形态和功能障碍之间的关系,并确定 VAT 重塑的程度是否与肥胖患者的肝损伤和代谢改变相关。

方法

我们分析了 40 名肥胖患者的数据,这些患者候选进行减肥手术,术中对肝脏和网膜进行了成对活检,通过免疫组织化学和 mRNA 表达研究来诊断 NAFLD 和 VAT 炎症。

结果

在我们的研究人群中,NAFLD 与 VAT CD68 巨噬细胞浸润(P =.04)、纤维化(P =.04)和微血管密度受损(P =.03)以及局部缺氧、凋亡和炎症标志物(UNC5B、CASP7、HIF1-α、IL-8、MIP2、WISP-1,均 P <.01)表达增加显著相关。VAT 炎症的程度与肝损伤的严重程度(脂肪变性、炎症、纤维化;均 P <.01)和糖代谢受损相关。

结论

在肥胖患者中,NAFLD 与 VAT 重塑的迹象呈剂量依赖性相关,这反映了更严重的临床代谢损伤。我们的研究描绘了 VAT 功能障碍的形态改变和新的介质,为未来治疗 NAFLD 及其代谢并发症提供了更多的知识。

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