Insulin resistance in morbid obesity - Reversal with intramyocellular fat depletion
Insulin resistance in morbid obesity - Reversal with intramyocellular fat depletion
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DOI：
10.2337/diabetes.51.1.144
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发表时间：
2002-01-01
期刊：
影响因子：
7.7
通讯作者：
Ferrannini, E
中科院分区：
文献类型：
--
作者：
Greco, AV;Mingrone, G;Ferrannini, E
肥胖是胰岛素抵抗的常见原因，并构成糖尿病的主要风险。骨骼肌内的脂肪异常沉积已被确定为肥胖相关的胰岛素抵抗的机制。我们检验了这样一个假设，即饮食性脂质剥夺可以选择性地消耗肌细胞内脂质，从而逆转胰岛素抵抗。对20名病态肥胖患者（BMI = 49 +/- 8 [平均值+/- SD] kg . m（2））和7名非肥胖对照受试者。患者在胆胰分流术（BPD; n = 8）后6个月进行再研究，BPD是一种主要诱导脂质吸收不良或低热量饮食的手术（n = 9）。在6个月时，BPD通过脂质吸收不良导致体重减轻33 +/- 10 kg（通过平坦的餐后甘油三酯曲线记录）。尽管达到BMI仍在肥胖范围内（39 +/- 8 kg）。m（-2）），胰岛素抵抗（23 +/- 3 mumol/min/kg去脂体重; P < 0.001 vs.对照组53 +/- 13）被完全逆转（52 +/- 11 mumol/min/kg去脂体重; NS vs.对照组）。与此同时，肌细胞内（而非血管周围或肌纤维间）脂质积聚减少（1.63 +/- 1.06至0.22 +/- 0.44评分单位; P < 0.01; NS vs.对照组0.07 +/- 0.19），Glut 4表达恢复，循环瘦素浓度正常化。在饮食组中，体重减轻14 +/- 12 kg伴随着胰岛素敏感性和肌细胞内脂质含量的非常适度的变化。我们的结论是，脂质剥夺选择性地消耗肌细胞内的脂质储存，并诱导正常的代谢状态（胰岛素介导的全身葡萄糖处置，细胞内胰岛素信号传导和循环瘦素水平），尽管持续过剩的总身体脂肪量。
Obesity is a frequent cause of insulin resistance and poses a major risk for diabetes. Abnormal fat deposition within skeletal muscle has been identified as a mechanism of obesity-associated insulin resistance. We tested the hypothesis that dietary lipid deprivation may selectively deplete intramyocellular lipids, thereby reversing insulin resistance. Whole-body insulin sensitivity (by the insulin clamp technique), intramyocellular lipids (by quantitative histochemistry on quadriceps muscle biopsies), muscle insulin action (as the expression of Glut4 glucose transporters), and postprandial lipemia were measured in 20 morbidly obese patients (BMI = 49 +/- 8 [mean +/- SD] kg . m(2)) and 7 nonobese control subjects. Patients were restudied 6 months later after biliopancreatic diversion (BPD; n = 8), an operation that induces predominant lipid malabsorption, or hypocaloric diet (n = 9). At 6 months, BPD had caused the loss of 33 +/- 10 kg through lipid malabsorption (documented by a flat postprandial triglyceride profile). Despite an attained BMI still in the obese range (39 +/- 8 kg . m(-2)), insulin resistance (23 +/- 3 mumol/min per kg of fat-free mass; P < 0.001 vs. 53 +/- 13 of control subjects) was fully reversed (52 +/- 11 mumol/min per kg of fat-free mass; NS versus control subjects). In parallel with this change, intramyocellular-but not perivascular or interfibrillar-lipid accumulation decreased (1.63 +/- 1.06 to 0.22 +/- 0.44 score units; P < 0.01; NS vs. 0.07 +/- 0.19 of control subjects), Glut4 expression was restored, and circulating leptin concentrations were normalized. In the diet group, a weight loss of 14 +/- 12 kg was accompanied by very modest changes in insulin sensitivity and intramyocellular lipid contents. We conclude that lipid deprivation selectively depletes intramyocellular lipid stores and induces a normal metabolic state (in terms of insulin-mediated whole-body glucose disposal, intracellular insulin signaling, and circulating leptin levels) despite a persistent excess of total body fat mass.