Babic Aleksandar M, Wang Hong-Wei, Lai Margaret J, Daniels Thomas G, Felbinger Thomas W, Burger Peter C, Stricker-Krongrad Alain, Wagner Denisa D
The CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA.
Mol Med. 2004 Jul-Dec;10(7-12):72-9. doi: 10.2119/2004-00038.Wagner.
Intercellular adhesion molecule 1 (ICAM-1) and beta2 integrins play critical roles in immune responses. ICAM-1 may also participate in regulation of energy balance because ICAM-1-deficient mice become obese on a high-fat diet. We show that mice deficient in these adhesion receptors are unable to respond to fasting by up-regulation of fatty acid oxidation. Normal mice, when fasted, exhibit reduced circulating neutrophil counts and increased ICAM-1 expression and neutrophil recruitment in liver. Mice lacking ICAM-1 or beta2 integrins fail to show these responses--instead they become hypoglycemic with steatotic livers. Fasting ICAM-1-deficient mice reduce insulin more slowly than wild-type mice. This produces fasting hyperinsulinemia that prevents activation of adenosine mono-phosphate (AMP)-activated protein kinase in muscles and liver, which results in decreased import of long chain fatty acids into mitochondria. Thus, we show a new role for immune cells and their adhesion receptors in regulating metabolic response to fasting.
细胞间黏附分子1（ICAM-1）和β2整合素在免疫反应中发挥关键作用。ICAM-1也可能参与能量平衡的调节，因为ICAM-1缺陷型小鼠在高脂饮食下会变得肥胖。我们发现，缺乏这些黏附受体的小鼠无法通过上调脂肪酸氧化来对禁食做出反应。正常小鼠禁食时，循环中性粒细胞计数减少，肝脏中ICAM-1表达增加，中性粒细胞募集增多。缺乏ICAM-1或β2整合素的小鼠未能表现出这些反应，相反，它们会出现低血糖并伴有肝脏脂肪变性。禁食的ICAM-1缺陷型小鼠比野生型小鼠更缓慢地降低胰岛素水平。这会导致禁食期间的高胰岛素血症，从而阻止肌肉和肝脏中腺苷单磷酸（AMP）激活的蛋白激酶的激活，进而导致长链脂肪酸进入线粒体的量减少。因此，我们揭示了免疫细胞及其黏附受体在调节对禁食的代谢反应中的新作用。
