Hotamisligil G S
Department of Genetics and Complex Diseases, School of Public Health, Harvard University, Boston, MA, USA.
Int J Obes (Lond). 2008 Dec;32 Suppl 7(Suppl 7):S52-4. doi: 10.1038/ijo.2008.238.
Obesity is associated with chronic low-grade inflammation. Inflammatory signals interfere with insulin action and disrupt metabolic homeostasis. The c-Jun N-terminal kinase (JNK) has been identified as a central mediator of insulin resistance. Recent studies showed that in obesity compromising endoplasmic reticulum (ER) function results in insulin resistance and type 2 diabetes that are dependent on JNK activation. In contrast, enhancing ER function in transgenic mice or by the use of chemical chaperones protects against diet-induced insulin resistance. Hence, ER stress and the related signaling networks present a critical mechanism underlying obesity-induced JNK activity, inflammatory response and insulin resistance.
肥胖与慢性低度炎症相关。炎症信号干扰胰岛素作用并破坏代谢稳态。c-Jun氨基末端激酶（JNK）已被确定为胰岛素抵抗的核心介质。最近的研究表明，在肥胖状态下，内质网（ER）功能受损会导致依赖JNK激活的胰岛素抵抗和2型糖尿病。相反，在转基因小鼠中增强ER功能或使用化学伴侣可预防饮食诱导的胰岛素抵抗。因此，内质网应激及相关信号网络是肥胖诱导的JNK活性、炎症反应和胰岛素抵抗的关键潜在机制。
