Characteristics of hepatic insulin-sensitive nonalcoholic fatty liver disease.
Characteristics of hepatic insulin-sensitive nonalcoholic fatty liver disease.
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DOI：
10.1002/hep4.1077
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发表时间：
2017-09
影响因子：
5.1
通讯作者：
Hirose T
中科院分区：
文献类型：
--
作者：
Shigiyama F;Kumashiro N;Furukawa Y;Funayama T;Takeno K;Wakui N;Ikehara T;Nagai H;Taka H;Fujimura T;Uchino H;Tamura Y;Watada H;Nemoto T;Shiraga N;Sumino Y;Hirose T
非酒精性脂肪性肝病（NAFLD）在2型糖尿病和肝细胞癌中起着至关重要的作用。主要的潜在发病机制是肝脏胰岛素抵抗。本研究的目的是描述肝脏胰岛素敏感性异常的NAFLD患者与肝脏胰岛素抵抗的NAFLD患者的特征。我们招募了26例NAFLD患者，并将其分为三组，根据使用稳定同位素的高胰岛素-正葡萄糖钳夹研究评估的肝脏胰岛素敏感性水平（HIS;高HIS，中HIS，低HIS）进行排名。高HIS组的肝脏胰岛素敏感性与非NAFLD瘦对照相同（内源性葡萄糖产生的钳夹抑制百分比分别为91.1% ± 5.2%和91.0% ± 8.5%），并显著高于低HIS组（66.6% ± 7.5%; P < 0.01）。评估了高HIS组和低HIS组的肥胖（皮下、内脏、肝内和肌肉脂质含量）、肝组织病理学和各种基因的表达水平（使用肝活检）、肌肉和脂肪组织胰岛素敏感性、血浆代谢物（通过代谢组学分析）、推定的生物标志物和生活方式，并进行了比较。其中，通过游离脂肪酸、血清高分子量脂联素和血浆三羧酸循环代谢产物（如柠檬酸和顺乌头酸）的钳位抑制百分比评估的脂肪组织胰岛素敏感性，高HIS组显著高于低HIS组。相比之下，在肥胖方面没有差异，包括通过质子磁共振波谱评估的肝内脂质含量（分别为28.3% ± 16.1%和20.4% ± 9.9%），肝脏组织病理学，其他假定的生物标志物和生活方式。结论：高水平的脂肪组织胰岛素敏感性、血清高分子量脂联素和血浆三羧酸循环代谢物是定义肝胰岛素敏感性NAFLD患者的独特特征，无论肝内脂质含量如何。（Hepatology Communications 2017;1：634-647）
Nonalcoholic fatty liver disease (NAFLD) plays a crucial role in type 2 diabetes and hepatocellular carcinoma. The major underlying pathogenesis is hepatic insulin resistance. The aim of the present study was to characterize patients with NAFLD with paradoxically normal hepatic insulin sensitivity relative to patients with NAFLD with hepatic insulin resistance. We recruited 26 patients with NAFLD and divided them into three groups ranked by the level of hepatic insulin sensitivity (HIS; high‐HIS, mid‐HIS, low‐HIS), as assessed by the hyperinsulinemic‐euglycemic clamp studies using stable isotope. Hepatic insulin sensitivity of the high‐HIS group was identical to that of the non‐NAFLD lean control (clamped percent suppression of endogenous glucose production, 91.1% ± 5.2% versus 91.0% ± 8.5%, respectively) and was significantly higher than that of the low‐HIS group (66.6% ± 7.5%; P < 0.01). Adiposity (subcutaneous, visceral, intrahepatic, and muscular lipid content), hepatic histopathology, and expression levels of various genes by using liver biopsies, muscle, and adipose tissue insulin sensitivity, plasma metabolites by metabolomics analysis, putative biomarkers, and lifestyles were assessed and compared between the high‐HIS and low‐HIS groups. Among these, adipose tissue insulin sensitivity assessed by clamped percent suppression of free fatty acid, serum high molecular weight adiponectin, and plasma tricarboxylic acid cycle metabolites, such as citric acid and cis‐aconitic acid, were significantly higher in the high‐HIS group compared to the low‐HIS group. In contrast, there were no differences in adiposity, including intrahepatic lipid content assessed by proton magnetic resonance spectroscopy (28.3% ± 16.1% versus 20.4% ± 9.9%, respectively), hepatic histopathology, other putative biomarkers, and lifestyles. Conclusion: High levels of adipose tissue insulin sensitivity, serum high molecular weight adiponectin, and plasma tricarboxylic acid cycle metabolites are unique characteristics that define patients with hepatic insulin‐sensitive NAFLD regardless of intrahepatic lipid content. (Hepatology Communications 2017;1:634–647)
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携带 patatin 样磷脂酶 3 基因变体的人类脂肪肝与胰岛素抵抗之间的关联。
影响因子：
7.7
作者：
Kantartzis K;Peter A;Machicao F;Machann J;Wagner S;Königsrainer I;Königsrainer A;Schick F;Fritsche A;Häring HU;Stefan N
通讯作者：
Stefan N
影响因子：
3.7
作者：
Kato K;Takamura T;Takeshita Y;Ryu Y;Misu H;Ota T;Tokuyama K;Nagasaka S;Matsuhisa M;Matsui O;Kaneko S
通讯作者：
Kaneko S
影响因子：
16.2
作者：
Lomonaco R;Bril F;Portillo-Sanchez P;Ortiz-Lopez C;Orsak B;Biernacki D;Lo M;Suman A;Weber MH;Cusi K
通讯作者：
Cusi K
影响因子：
16.2
作者：
Lehmann R;Franken H;Dammeier S;Rosenbaum L;Kantartzis K;Peter A;Zell A;Adam P;Li J;Xu G;Königsrainer A;Machann J;Schick F;Hrabé de Angelis M;Schwab M;Staiger H;Schleicher E;Gastaldelli A;Fritsche A;Häring HU;Stefan N
通讯作者：
Stefan N
影响因子：
13.5
作者：
Bril, Fernando;Barb, Diana;Cusi, Kenneth
通讯作者：
Cusi, Kenneth