Increased fat accumulation in liver may link insulin resistance with subcutaneous abdominal adipocyte enlargement, visceral adiposity, and hypoadiponectinemia in obese individuals
Increased fat accumulation in liver may link insulin resistance with subcutaneous abdominal adipocyte enlargement, visceral adiposity, and hypoadiponectinemia in obese individuals
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DOI：
10.1093/ajcn/87.2.295
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发表时间：
2008-02-01
影响因子：
7.1
通讯作者：
Bunt, Joy C.
中科院分区：
文献类型：
--
作者：
Koska, Juraj;Stefan, Norbert;Bunt, Joy C.
工作背景：来自皮下腹部脂肪组织（SAT）的脂肪细胞的增加、肝内脂质含量（IHL）、肌细胞内脂质含量（IMCL）的增加以及低循环脂联素浓度与胰岛素抵抗相关。目的：由于脂联素增加骨骼肌和肝脏中的脂肪氧化，而SAT中脂联素基因的表达与脂肪细胞大小呈负相关，我们假设低脂联素血症通过增加IMCL和IHL将肥厚性肥胖与胰岛素抵抗联系起来。设计：53名肥胖的皮马印第安人，平均（+/- SD）年龄为27 +/- 8岁，体脂为35 +/-5%，和正常的血糖调节（根据WHO 1999标准，正常空腹和2小时葡萄糖浓度）进行正常血糖-高胰岛素钳夹，SAT和股外侧肌活检，以及腹部磁共振成像。脂肪细胞直径（AD）与体脂（P < 0.0001）和IHL（根据肝脏磁共振成像强度估计; P = 0.047）呈正相关。AD与血浆脂联素和IMCL之间无相关性。血浆脂联素与11型IMCL（IIA，P = 0.004; IIX，P = 0.009）或IHL（P = 0.02）呈负相关。在多变量分析中，血浆脂联素、AD和内脏脂肪组织（VAT）独立预测IHL。低胰岛素介导的葡萄糖处置与低血浆脂联素（P = 0.02）和高IHL（P = 0.0003）、SAT（P = 0.02）和VAT（P = 0.04）相关。高IHL是唯一的预测减少胰岛素介导的抑制肝脏葡萄糖的生产（P = 0.02）和胰岛素介导的葡萄糖处置在多变量analysis.Conclusions的唯一独立的预测因素：在肝脏中的脂质含量增加可能独立链接低脂联素血症，肥厚性肥胖，内脏脂肪增多与外周和肝脏胰岛素抵抗。
Background: Enlargement of adipocytes from subcutaneous abdominal adipose tissue (SAT), increased intrahepatic lipid content (IHL), intramyocellular lipid content (IMCL), and low circulating adiponectin concentrations are associated with insulin resistance.Objective: Because adiponectin increases fat oxidation in skeletal muscle and liver, and the expression of the adiponectin gene in SAT is inversely associated with adipocyte size, we hypothesized that hypoadiponectinemia links hypertrophic obesity with insulin resistance via increased IMCL and IHL.Design: Fifty-three obese Pima Indians with a mean ( +/- SD) age of 27 +/- 8 y, body fat of 35 +/- 5%, and normal glucose regulation (normal fasting and 2-h glucose concentration per WHO 1999 criteria) underwent euglycemic-hyperinsulinemic clamp, biopsies of SAT and vastus lateral is muscle, and magnetic resonance imaging of the abdomen.Results: Adipocyte diameter (AD) correlated positively with body fat (P < 0.0001) and IHL (estimated from magnetic resonance imaging intensity of liver; P = 0.047). No association was found between AD and plasma adiponectin or IMCL. Plasma adiponectin negatively correlated with type 11 IMCL (IIA, P = 0.004; IIX, P = 0.009) or IHL (P = 0.02). In a multivariate analysis, plasma adiponectin, AD, and visceral adipose tissue (VAT) independently predicted IHL. Low insulin-mediated glucose disposal was associated with low plasma adiponectin (P = 0.02) and high IHL (P = 0.0003), SAT (P = 0.02), and VAT (P = 0.04). High IHL was the only predictor of reduced insulin-mediated suppression of hepatic glucose production (P = 0.02) and the only independent predictor of insulin-mediated glucose disposal in a multivariate analysis.Conclusions: Increased lipid content in the liver may independently link hypoadiponectinemia, hypertrophic obesity, and increased visceral adiposity with peripheral and hepatic insulin resistance.