Vallerie Sara N, Furuhashi Masato, Fucho Raquel, Hotamisligil Gökhan S
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
PLoS One. 2008 Sep 5;3(9):e3151. doi: 10.1371/journal.pone.0003151.
It has been established that c-Jun N-terminal kinase 1 (JNK1) is essential to the pathogenesis of insulin resistance and type 2 diabetes. Although JNK influences inflammatory signaling pathways, it remains unclear whether its activity in macrophages contributes to adipose tissue inflammation and ultimately to the regulation of systemic metabolism. To address whether the action of this critical inflammatory kinase in bone marrow-derived elements regulates inflammatory responses in obesity and is sufficient and necessary for the deterioration of insulin sensitivity, we performed bone marrow transplantation studies with wild type and JNK1-deficient mice. These studies illustrated that JNK1-deficiency in the bone marrow-derived elements (BMDE) was insufficient to impact macrophage infiltration or insulin sensitivity despite modest changes in the inflammatory profile of adipose tissue. Only when the parenchymal elements lacked JNK1 could we demonstrate a significant increase in systemic insulin sensitivity. These data indicate that while the JNK1 activity in BMDE is involved in metabolic regulation and adipose milieu, it is epistatic to JNK1 activity in the parenchymal tissue for regulation of metabolic homeostasis.
已有研究证实，c-Jun氨基末端激酶1（JNK1）对胰岛素抵抗和2型糖尿病的发病机制至关重要。尽管JNK影响炎症信号通路，但其在巨噬细胞中的活性是否导致脂肪组织炎症并最终影响全身代谢调节仍不清楚。为了探讨这种关键炎症激酶在骨髓来源细胞中的作用是否调节肥胖中的炎症反应，以及对胰岛素敏感性恶化是否充分必要，我们用野生型和JNK1缺陷型小鼠进行了骨髓移植研究。这些研究表明，尽管脂肪组织炎症特征有适度变化，但骨髓来源细胞（BMDE）中JNK1缺陷不足以影响巨噬细胞浸润或胰岛素敏感性。只有当实质细胞缺乏JNK1时，我们才能证明全身胰岛素敏感性显著增加。这些数据表明，虽然BMDE中的JNK1活性参与代谢调节和脂肪环境，但在调节代谢稳态方面，它对实质组织中JNK1的活性是上位性的。
