Saturated fatty acids induce c-Src clustering within membrane subdomains, leading to JNK activation.
Saturated fatty acids induce c-Src clustering within membrane subdomains, leading to JNK activation.
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DOI：
10.1016/j.cell.2011.08.034
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发表时间：
2011-09-30
期刊：
影响因子：
64.5
通讯作者：
Karin M
中科院分区：
文献类型：
--
作者：
Holzer RG;Park EJ;Li N;Tran H;Chen M;Choi C;Solinas G;Karin M
饱和脂肪酸 (FA) 会对健康产生不利影响，并且比不饱和 FA 更容易导致胰岛素抵抗和 2 型糖尿病，其中一些脂肪酸会产生保护和有益作用。饱和 FA（而非不饱和 FA）会激活 Jun N 末端激酶 (JNK)，该激酶与小鼠和男性的肥胖和胰岛素抵抗有关。然而，尚不清楚如何区分饱和FA和不饱和FA。我们现在证明，饱和 FA 可以通过改变 c-Src 的膜分布来激活 JNK 并诱导胰岛素抵抗，导致其划分为细胞内膜子域，并在其中被激活。相反，已知对葡萄糖代谢具有有益作用的不饱和 FA 可阻止 c-Src 膜的分配和激活（这取决于其肉豆蔻酰化），并阻止 JNK 激活。食用引起糖尿病的高脂肪饮食会导致脂肪细胞去污剂不溶性膜亚域内的 c-Src 分配和激活。
Saturated fatty acids (FA) exert adverse health effects and are more likely to cause insulin resistance and type 2 diabetes than unsaturated FA, some of which exert protective and beneficial effects. Saturated FA, but not unsaturated FA, activate Jun N terminal kinase (JNK), which has been linked to obesity and insulin resistance in mice and men. However, it is unknown how saturated and unsaturated FA are discriminated. We now demonstrate that saturated FA activate JNK and induce insulin resistance by altering the membrane distribution of c-Src, causing it to partition into intracellular membrane subdomains where it may become activated. Conversely, unsaturated FA with known beneficial effects on glucose metabolism prevent c-Src membrane partitioning and activation, which are dependent on its myristoylation, and block JNK activation. Consumption of a diabetogenic high fat diet causes the partitioning and activation of c-Src within detergent insoluble membrane subdomains of adipocytes.
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