Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, Zurich, Switzerland.
Am J Physiol Endocrinol Metab. 2013 Aug 1;305(3):E388-95. doi: 10.1152/ajpendo.00179.2013. Epub 2013 Jun 4.
High-fat feeding for 3-4 days impairs glucose tolerance and hepatic insulin sensitivity. However, it remains unclear whether the evolving hepatic insulin resistance is due to acute lipid overload or the result of induced adipose tissue inflammation and consequent dysfunctional adipose tissue-liver cross-talk. In the present study, feeding C57Bl6/J mice a fat-enriched diet [high-fat diet (HFD)] for 4 days induced glucose intolerance, hepatic insulin resistance (as assessed by hyperinsulinemic euglycemic clamp studies), and hepatic steatosis as well as adipose tissue inflammation (i.e., TNFα expression) compared with standard chow-fed mice. Adipocyte-specific depletion of the antiapoptotic/anti-inflammatory factor Fas (CD95) attenuated adipose tissue inflammation and improved glucose tolerance as well as hepatic insulin sensitivity without altering the level of hepatic steatosis induced by HFD. In summary, our results identify adipose tissue inflammation and resulting dysfunctional adipose tissue-liver cross-talk as an early event in the development of HFD-induced hepatic insulin resistance.
高脂喂养 3-4 天会损害葡萄糖耐量和肝胰岛素敏感性。然而，目前尚不清楚不断发展的肝胰岛素抵抗是由于急性脂质过载，还是由于诱导的脂肪组织炎症和随之而来的功能失调的脂肪组织-肝脏相互作用所致。在本研究中，与标准喂养的小鼠相比，用高脂肪饮食（HFD）喂养 C57Bl6/J 小鼠 4 天会导致葡萄糖不耐受、肝胰岛素抵抗（通过高胰岛素正葡萄糖钳夹研究评估）和肝脂肪变性，以及脂肪组织炎症（即 TNFα 表达）。脂肪细胞特异性敲除抗凋亡/抗炎因子 Fas（CD95）可减轻脂肪组织炎症，改善葡萄糖耐量和肝胰岛素敏感性，而不改变 HFD 诱导的肝脂肪变性水平。总之，我们的结果表明，脂肪组织炎症和由此产生的功能失调的脂肪组织-肝脏相互作用是 HFD 诱导的肝胰岛素抵抗发展的早期事件。
