Differential responses of visceral and subcutaneous fat depots to nutrients

Differential responses of visceral and subcutaneous fat depots to nutrients
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DOI:
10.2337/diabetes.54.3.672
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发表时间:
2005-03-01
期刊:
影响因子:
7.7
通讯作者:
Barzilai, N
Barzilai, N
中科院分区:
医学1区
文献类型:
--
作者:
Einstein, FH;Atzmon, G;Barzilai, N

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内脏脂肪增多是代谢综合征的关键组成部分。在禁食状态下,内脏脂肪和皮下脂肪中脂肪衍生肽(FDP)的差异基因表达模式已被表征。在这里,我们研究了营养物质的输送是否差异影响内脏脂肪与皮下脂肪(在进食状态下)中FDP的表达。我们用钳夹技术增加了正常大鼠(n = 16)高血糖或高胰岛素血症的葡萄糖流入脂肪组织的速率。葡萄糖摄取与FDP表达增加相关,包括内脏脂肪中FDP的表达增加5倍,脂联素增加2倍,瘦素增加15倍,纤溶酶原激活抑制剂1增加10倍,血管紧张素原增加4倍,但皮下脂肪中FDP的表达明显减少。主要来自脂肪组织的血管/基质/巨噬细胞成分的细胞因子表达增加不太明显。葡萄糖胺的输注放大了通过增加葡萄糖摄取到脂肪组织中所获得的结果,这表明通过己糖胺生物合成途径的通量可以作为“营养感测”的机制。“内脏脂肪中FDPs的营养依赖性表达也与几种FDPs的血浆水平增加有关。由于生物传感途径可以动态地将每日食物摄入量与重要FDP的异常血浆水平相结合,因此我们挑战了禁食后获得血浆水平以评估代谢综合征风险因素的做法。
Increased visceral adiposity is a pivotal component of the metabolic syndrome. Differential gene expression patterns of fat-derived peptides (FDPs) in visceral fat and subcutaneous fat have been characterized in the fasting state. Here we examined whether delivery of nutrients differentially affects the expression of FDPs in visceral fat versus subcutaneous fat (in the fed state). We increased the rate of glucose flux into adipose tissue of normal rats (n = 16) by hyperglycemia or hyperinsulinemia using the clamp technique. Glucose uptake was associated with increased expression of FDPs, including resistin (similar to5-fold), adiponectin (similar to2fold), leptin (similar to15-fold), plasminogen activating inhibitor-1 (similar to10-fold), and angiotensinogen (similar to4-fold) in visceral fat, but markedly less in subcutaneous fat. Cytokine expression de-rived mainly from vascular/ stromal/macrophage components of adipose tissue was less dramatically increased. Infusion of glucosamine amplified the results obtained by increasing glucose uptake into adipose tissue, suggesting that flux through the hexosamine biosynthetic pathway may serve as a mechanism for "nutrient sensing." Nutrient-dependent expression of FDPs in visceral fat was also associated with increased plasma levels of several FDPs. Because a biologic sensing pathway can dynamically couple daily food intake to abnormal plasma levels of important FDPs, we challenge the practice of obtaining plasma levels after fasting to assess risk factors for metabolic syndrome.