Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
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DOI：
10.1073/pnas.0904944106
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发表时间：
2009-09-08
影响因子：
11.1
通讯作者：
Klein, Samuel
中科院分区：
文献类型：
--
作者：
Fabbrini, Elisa;Magkos, Faidon;Klein, Samuel
内脏脂肪组织（VAT）是肥胖相关代谢紊乱的重要危险因素。因此，降低增值税已成为肥胖管理的一个关键目标。然而，VAT与肝内甘油三酯（IHTG）含量相关，因此IHTG而不是VAT可能是代谢性疾病的更好标志物。我们通过评估肥胖受试者组（IHTG含量不同（高或正常）但VAT体积匹配或VAT体积不同（高或低）但IHTG含量匹配），确定了IHTG和VAT与代谢功能的独立相关性。采用稳定同位素示踪技术和正常血糖-高胰岛素钳夹技术测定胰岛素敏感性和极低密度脂蛋白-甘油三酯（VLDL-TG）分泌率。获得组织活检以评价参与异位甘油三酯蓄积的细胞因子。肝脏、脂肪组织和肌肉胰岛素敏感性分别降低了41%、13%和36%（P < 0.01），而VLDL-甘油三酯分泌率几乎是正常的两倍（P < 0.001），在IHTG含量高于正常的受试者中，与VAT匹配。在IHTG含量匹配的具有不同VAT体积的受试者之间没有观察到胰岛素敏感性或VLDL-TG分泌的差异。IHTG增高者脂肪组织CD 36表达降低（P < 0.05），骨骼肌CD 36表达升高（P < 0.05）。这些数据表明，IHTG，而不是VAT，是与肥胖相关的代谢紊乱的更好的标志物。此外，组织脂肪酸转运的改变可能通过将血浆脂肪酸从脂肪组织向其他组织的摄取重新定向而参与异位甘油三酯蓄积的发病机制。
Visceral adipose tissue (VAT) is an important risk factor for obesity-related metabolic disorders. Therefore, a reduction in VAT has become a key goal in obesity management. However, VAT is correlated with intrahepatic triglyceride (IHTG) content, so it is possible that IHTG, not VAT, is a better marker of metabolic disease. We determined the independent association of IHTG and VAT to metabolic function, by evaluating groups of obese subjects, who differed in IHTG content (high or normal) but matched on VAT volume or differed in VAT volume (high or low) but matched on IHTG content. Stable isotope tracer techniques and the euglycemic-hyperinsulinemic clamp procedure were used to assess insulin sensitivity and very-low-density lipoprotein-triglyceride (VLDL-TG) secretion rate. Tissue biopsies were obtained to evaluate cellular factors involved in ectopic triglyceride accumulation. Hepatic, adipose tissue and muscle insulin sensitivity were 41, 13, and 36% lower (P < 0.01), whereas VLDL-triglyceride secretion rate was almost double (P < 0.001), in subjects with higher than normal IHTG content, matched on VAT. No differences in insulin sensitivity or VLDL-TG secretion were observed between subjects with different VAT volumes, matched on IHTG content. Adipose tissue CD36 expression was lower (P < 0.05), whereas skeletal muscle CD36 expression was higher (P < 0.05), in subjects with higher than normal IHTG. These data demonstrate that IHTG, not VAT, is a better marker of the metabolic derangements associated with obesity. Furthermore, alterations in tissue fatty acid transport could be involved in the pathogenesis of ectopic triglyceride accumulation by redirecting plasma fatty acid uptake from adipose tissue toward other tissues.