Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men.
Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men.
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DOI：
10.1210/jcem.87.7.8638
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发表时间：
2002-07
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通讯作者：
Anneli Seppälä‐Lindroos;S. Vehkavaara;A. Häkkinen;Takashi Goto;J. Westerbacka;Anssi Sovijärvi;Juha Halav
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文献类型：
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作者：
Anneli Seppälä‐Lindroos;S. Vehkavaara;A. Häkkinen;Takashi Goto;J. Westerbacka;Anssi Sovijärvi;Juha Halav
我们确定了肝脏胰岛素敏感性的个体间差异是否可以归因于独立于肥胖的肝脏脂肪含量（LFAT）的变化。我们招募了30名健康的非糖尿病男性，（通过质子光谱测定）;腹腔内、皮下和总（通过磁共振成像测定）脂肪;内源性葡萄糖产生率（R（a））的胰岛素敏感性和血清FFA的抑制[正葡萄糖胰岛素钳夹结合[3-（3）H]葡萄糖]（0-300 min）;胰岛素输注速率，0.3 mU/kg.min，120-300 min]。根据他们的中位脂肪含量，这些男性被分为低（平均值+/- SD，1.7 +/- 0.2%）和高（10.5 +/- 2.0%）LFAT组。低和高LFAT组在年龄方面具有可比性（44 +/- 2 vs. 42 +/- 2岁），体重指数（25 +/- 1 vs. 26 +/- 1 kg/m（2）），腰臀比（0.953 +/- 0.013 vs. 0.953 +/- 0.013）、最大摄氧量（35.6 +/- 1.5 vs. 33.5 +/- 1.5 ml/kg.min）和腹腔内、皮下和总脂肪。与低LFAT组相比，高LFAT组具有胰岛素抵抗的几个特征，包括空腹高胰岛素血症（7.3 +/- 0.6 vs. 5.3 +/- 0.6 mU/L; P < 0.02，高vs.低LFAT）高甘油三酯血症（1.4 +/- 0.2对0.9 +/- 0.1 mmol/L; P < 0.02），低高密度脂蛋白（HDL）胆固醇浓度（1.4 +/- 0.1对1.6 +/- 0.1 mmol/L; P < 0.05），以及更高的动态24小时收缩压（130 +/- 3对122 +/- 3 mm Hg; P < 0.05）。基础葡萄糖R（a）和血清FFA在两组之间是相似的，而在240-300分钟期间，葡萄糖R（a）的胰岛素抑制[51 +/- 8 vs. 20 +/- 12 mg/m2.min（P < 0.05）或低于基础值-55 +/- 7 vs. -85 +/- 12%（P < 0.05，高与低LFAT）]和血清FFA（299 +/- 33与212 +/- 13微摩尔/升; 240-300分钟; P < 0.02）在高LFAT组与低LFAT组相比受损。高LFAT组（141 +/- 12 mg/m2.min）和低LFAT组（156 +/- 14 mg/m2.min; P = NS）的胰岛素刺激葡萄糖Rd相似。肝脏中的脂肪积聚与体重指数、腹内肥胖和总体肥胖无关，其特征在于正常体重和中度超重受试者中胰岛素抵抗的几个特征。
We determined whether interindividual variation in hepatic insulin sensitivity could be attributed to variation in liver fat content (LFAT) independent of obesity. We recruited 30 healthy nondiabetic men whose LFAT (determined by proton spectroscopy); intraabdominal, sc, and total (determined by magnetic resonance imaging) fat; and insulin sensitivity of endogenous glucose rate of production (R(a)) and suppression of serum FFA [euglycemic insulin clamp combined with [3-(3)H]glucose (0-300 min); insulin infusion rate, 0.3 mU/kg.min, 120-300 min] were measured. The men were divided into groups of low (mean +/- SD, 1.7 +/- 0.2%) and high (10.5 +/- 2.0%) LFAT based on their median fat content. The low and high LFAT groups were comparable with respect to age (44 +/- 2 vs. 42 +/- 2 yr), body mass index (25 +/- 1 vs. 26 +/- 1 kg/m(2) ), waist to hip ratio (0.953 +/- 0.013 vs. 0.953 +/- 0.013), maximal oxygen uptake (35.6 +/- 1.5 vs. 33.5 +/- 1.5 ml/kg.min), and intraabdominal, sc, and total fat. The high compared with the low LFAT group had several features of insulin resistance, including fasting hyperinsulinemia (7.3 +/- 0.6 vs. 5.3 +/- 0.6 mU/liter; P < 0.02, high vs. low LFAT) hypertriglyceridemia (1.4 +/- 0.2 vs. 0.9 +/- 0.1 mmol/liter; P < 0.02), a low high density lipoprotein (HDL) cholesterol concentration (1.4 +/- 0.1 vs. 1.6 +/- 0.1 mmol/liter; P < 0.05), and a higher ambulatory 24-h systolic blood pressure (130 +/- 3 vs. 122 +/- 3 mm Hg; P < 0.05). Basal glucose R(a) and serum FFA were comparable between the groups, whereas insulin suppression of glucose R(a) [51 +/- 8 vs. 20 +/- 12 mg/m(2).min during 240-300 min (P < 0.05) or -55 +/- 7 vs. -85 +/- 12% below basal (P < 0.05, high vs. low LFAT)] and of serum FFA (299 +/- 33 vs. 212 +/- 13 micromol/liter; 240-300 min; P < 0.02) were impaired in the high compared with the low LFAT group. Insulin stimulation of glucose Rd were comparable in the men with high LFAT (141 +/- 12 mg/m(2).min) and those with low LFAT (156 +/- 14 mg/m(2).min; P = NS). Fat accumulation in the liver is, independent of body mass index and intraabdominal and overall obesity, characterized by several features of insulin resistance in normal weight and moderately overweight subjects.