Structural and inflammatory heterogeneity in subcutaneous adipose tissue: Relation with liver histopathology in morbid obesity

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• 作者：Joan Tordjman¹ ; ² ; ^{joan.tordjman@crc.jussieu.fr} ; Adeline Divoux² ; Edi Prifti² ; Christine Poitou¹ ; ² ; ³ ; Veronique Pelloux¹ ; ² ; Danielle Hugol⁴ ; Arnaud Basdevant¹ ; ² ; ³ ; Jean-Luc Bouillot⁵ ; Jean-Marc Chevallier⁶ ; Pierre Bedossa⁷ ; Michè ; le Guerre-Millo¹ ; ² ; Karine Clement¹ ; ² ; ³
• 关键词：NAFLD ; non-alcoholic fatty liver disease ; VAT ; visceral adipose tissue ; SAT ; subcutaneous adipose tissue ; sSAT ; superficial SAT ; dSAT ; deep SAT ; NASH ; non-alcoholic steatohepatitis ; QUICKI ; quantitative insulin sensitivity check index ; CSF3 ; colony-stimul
• 刊名：Journal of Hepatology
• 出版年：2012
• 期刊代码：162_01688278
• 类别：med
• 出版时间：May, 2012
• 卷：56
• 期：5
• 页码：1152-1158
• 文件大小：1043 K

摘要

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Background & Aims

In addition to total body fat, the regional distribution and inflammatory status of enlarged adipose tissue are strongly associated with metabolic co-morbidities of obesity. We recently showed that the severity of histological liver lesions related to obesity increases with the amount of macrophage accumulation in visceral adipose tissue (VAT), while no association was found with the subcutaneous adipose tissue (SAT). In the abdominal region, SAT is anatomically divided into two layers, i.e. superficial (sSAT) and deep (dSAT). The aim of the present study was to test the hypothesis that these distinct compartments differentially contribute to hepatic alterations in obesity.

Methods

Biopsies of the liver, sSAT, dSAT, and VAT were collected in 45 subjects with morbid obesity (age 43.7 卤 1.6 years; BMI 48.5 卤 1.2 kg/m²) during bariatric surgery. Large scale gene expression analysis was performed to identify the pathways that discriminate sSAT from dSAT. Adipose tissue macrophages were quantified by immunohistochemistry using HAM56 antibody in subjects scored for liver histopathology.

Results

An inflammatory gene pattern discriminates between sSAT and dSAT. dSAT displayed an intermediate level of macrophage accumulation between sSAT and VAT. The abundance of macrophages in dSAT, but not in sSAT, was significantly increased in patients with non-alcoholic steatohepatitis (NASH) and/or fibroinflammatory hepatic lesions.

Conclusions

These data show distinct gene signature and macrophage abundance in the two compartments of SAT, with dSAT more closely related to VAT than to sSAT in terms of inflammation and relation with the severity of liver diseases in morbid obesity.