Bekaert Marlies, Ouwens D Margriet, Hörbelt Tina, Van de Velde Frederique, Fahlbusch Pia, Herzfeld de Wiza Daniella, Van Nieuwenhove Yves, Calders Patrick, Praet Marleen, Hoorens Anne, Geerts Anja, Verhelst Xavier, Kaufman Jean-Marc, Lapauw Bruno
Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
German Diabetes Center, Institute for Clinical Biochemistry and Pathobiochemistry, Duesseldorf, Germany.
Obesity (Silver Spring). 2016 Dec;24(12):2544-2552. doi: 10.1002/oby.21674. Epub 2016 Oct 21.
This study aimed to evaluate whether circulating levels and/or visceral adipose tissue (VAT) expression of recently described adipokines associate with histopathological severity of nonalcoholic fatty liver disease (NAFLD), independent of obesity and insulin resistance.
Serum levels of adiponectin, omentin, chemerin, monocyte chemoattractant protein-1, and secreted frizzled-related protein 4 were measured using enzyme-linked immunosorbent assay in 81 patients with obesity and NAFLD and 18 lean control subjects. Expression in VAT was measured using real-time PCR and histopathological grading was scored using the NAFLD activity score (NAS).
When NAFLD patients were subdivided into groups with simple steatosis, borderline nonalcoholic steatohepatitis (NASH), and NASH, adiponectin serum levels and omentin expression were lower in NASH versus simple steatosis patients. Serum adiponectin was generally lower with higher histopathological grading. Chemerin VAT expression was negatively associated with NAS (r = -0.331, P = 0.022) and steatosis score (r = -0.335, P = 0.020), independent of age, BMI, and HOMA-IR. In addition, adjusting for chemerin VAT expression in a multivariate model explained part of the association between NAS and HOMA-IR.
These findings suggest that lower VAT expression of chemerin in patients with obesity may be involved in the pathophysiology of hepatic steatosis, potentially by modulating the link between insulin resistance and NAFLD.
本研究旨在评估最近描述的脂肪因子的循环水平和/或内脏脂肪组织（VAT）表达是否与非酒精性脂肪性肝病（NAFLD）的组织病理学严重程度相关，独立于肥胖和胰岛素抵抗。
采用酶联免疫吸附测定法测量了81例肥胖和NAFLD患者及18例瘦对照者血清中脂联素、网膜素、趋化素、单核细胞趋化蛋白-1和分泌型卷曲相关蛋白4的水平。使用实时聚合酶链反应测量VAT中的表达，并使用NAFLD活动评分（NAS）对组织病理学分级进行评分。
当将NAFLD患者分为单纯性脂肪变性、临界非酒精性脂肪性肝炎（NASH）和NASH组时，NASH患者的脂联素血清水平和网膜素表达低于单纯性脂肪变性患者。血清脂联素通常随着组织病理学分级升高而降低。趋化素VAT表达与NAS（r = -0.331，P = 0.022）和脂肪变性评分（r = -0.335，P = 0.020）呈负相关，独立于年龄、体重指数和稳态模型评估的胰岛素抵抗（HOMA-IR）。此外，在多变量模型中对趋化素VAT表达进行校正解释了NAS与HOMA-IR之间关联的部分原因。
这些发现表明，肥胖患者VAT中趋化素表达降低可能参与了肝脂肪变性的病理生理过程，可能是通过调节胰岛素抵抗与NAFLD之间的联系。
