Ectopic fat accumulation and distant organ-specific insulin resistance in Japanese people with nonalcoholic fatty liver disease.
Ectopic fat accumulation and distant organ-specific insulin resistance in Japanese people with nonalcoholic fatty liver disease.
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DOI：
10.1371/journal.pone.0092170
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kaneko S
中科院分区：
文献类型：
--
作者：
Kato K;Takamura T;Takeshita Y;Ryu Y;Misu H;Ota T;Tokuyama K;Nagasaka S;Matsuhisa M;Matsui O;Kaneko S
本研究的目的是研究非酒精性脂肪性肝病(NAFLD)患者胰岛素靶器官中异位脂肪与器官特异性胰岛素抵抗(IR)的关系。用正常血糖高胰岛素钳夹结合示踪剂葡萄糖([6，6-2H2]葡萄糖)测定69例NAFLD患者肝脏(肝脏葡萄糖生成量(HGP)×空腹血浆胰岛素(FPI)和胰岛素[%HGP]抑制HGP)、骨骼肌(胰岛素刺激葡萄糖处理[RD])和脂肪组织(胰岛素[%FFA]抑制FFA)的器官特异性IR。分别通过肝脏活检、质子磁共振波谱和生物电阻抗分析测量肝脏脂肪、心肌细胞内脂质(IMCL)和身体成分。Hgp×Fpi与Rd(r = −0.57，P&t；0.001)、%HGP与%FFA(r = 0.38，P&t；0.01)、Rd与%FFA(r = 0.27，P<；0.05)呈显著正相关。肝脏脂肪变性评分与RD呈负相关(r = −0.47，P<；0.001)，与Hgp×Fpi呈负相关(r = 0.43，P<；0.001)。同样，肝内脂质与RD呈负相关(r = −0.32，P<；0.05)。IMCL与RD无相关性(r = −为0.16，P = 为0.26)。脂肪质量及其百分比与Hgp×Fpi(r = 0.50，P&t；0.001；r = 0.48，P<；0.001)和RD(r = −0.59，P<；0.001；r = −0.52，P<；0.001)相关，但与%FFA(r = −0.21，P = 0.10；r = −0.001，P = 0.99)无关。出乎意料的是，骨骼肌和脂肪组织中的脂肪积累与器官特异性胰岛素抵抗无关。相反，肝脏脂肪不仅与肝脏IR有关，而且与骨骼肌IR有关，这表明脂肪肝在全身IR中起着中心作用，肝脏和骨骼肌之间存在一个网络。
The aim of this study was to examine the association between ectopic fat and organ-specific insulin resistance (IR) in insulin-target organs in patients with nonalcoholic fatty liver disease (NAFLD). Organ-specific IR in the liver (hepatic glucose production (HGP)×fasting plasma insulin (FPI) and suppression of HGP by insulin [%HGP]), skeletal muscle (insulin-stimulated glucose disposal [Rd]), and adipose tissue (suppression of FFA by insulin [%FFA]) was measured in 69 patients with NAFLD using a euglycemic hyperinsulinemic clamp with tracer infusion ([6,6-2H2]glucose). Liver fat, intramyocellular lipid (IMCL), and body composition were measured by liver biopsy, proton magnetic resonance spectroscopy, and bioelectrical impedance analysis, respectively. HGP×FPI was significantly correlated with Rd (r = −0.57, P<0.001), %HGP with %FFA (r = 0.38, P<0.01), and Rd with %FFA (r = 0.27, P<0.05). Liver steatosis score was negatively associated with Rd (r = −0.47, P<0.001) as well as with HGP×FPI (r = 0.43, P<0.001). Similarly, intrahepatic lipid was negatively associated with Rd (r = −0.32, P<0.05). IMCL was not associated with Rd (r = −0.16, P = 0.26). Fat mass and its percentage were associated with HGP×FPI (r = 0.50, P<0.001; r = 0.48, P<0.001, respectively) and Rd (r = −0.59, P<0.001; r = −0.52, P<0.001, respectively), but not with %FFA (r = −0.21, P = 0.10; r = −0.001, P = 0.99, respectively). Unexpectedly, fat accumulation in the skeletal muscle and adipose tissue was not associated with organ-specific IR. Instead, liver fat was associated not only with hepatic IR but also with skeletal muscle IR, suggesting a central role of fatty liver in systemic IR and that a network exists between liver and skeletal muscle.
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影响因子：
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