Surgical removal of visceral fat reverses hepatic insulin resistance

Surgical removal of visceral fat reverses hepatic insulin resistance
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DOI:
10.2337/diabetes.48.1.94
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发表时间:
1999-01-01
期刊:
影响因子:
7.7
通讯作者:
Rossetti, L
Rossetti, L
中科院分区:
医学1区
文献类型:
--
作者:
Barzilai, N;She, L;Rossetti, L

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We directly examined whether visceral fat (VF) modulates hepatic insulin action by randomizing moderately obese (body wt similar to 400 g) Sprague-Dawley rats to either surgical removal of epididymal and perinephric fat pads (VF-: n = 9) or a sham operation (VF+; n = 11). Three weeks later, total VF was fourfold increased (8.5 +/- 1.2 vs;. 2.1 +/- 0.3 g, P < 0.001) in the VF+ compared with the VF- group, but whole-body fat mass (determined using (H2O)-H-3) was not significantly different, The rates of insulin infusion required to maintain plasma glucose levels and basal hepatic glucose production in the presence of hepatic-pancreatic clamp were markedly increased in VF- compared with VF+ rats (0.57 +/- 0.02 vs. 1.22 +/- 0.19 mU.kg(-1).min(-1), P < 0.001), Similarly, plasma insulin levels were more than twofold higher in the VF+ group (P < 0.001). The heightened hepatic insulin sensitivity is supported by the decrease in gene expression of both glucose-6-phosphatase and PEPCK and by physiological hyperinsulinemia in VF- but not VF+ rats. The improvement in hepatic Insulin sensitivity in VF- rats was also supported by a similar to 70% decrease in the plasma levels of insulin-like growth factor binding protein-1, a marker of insulin's transcription regulation in the liver. The removal of PF pads also resulted In marked decreases in the gene expression of tumor necrosis factor-alpha (by 72%) and leptin (by 60%) in subcutaneous fat. We conclude that visceral fat is: a potent modulator of insulin action on hepatic glucose production and gene expression.