High-fat diet in a mouse insulin-resistant model induces widespread rewiring of the phosphotyrosine signaling network
High-fat diet in a mouse insulin-resistant model induces widespread rewiring of the phosphotyrosine signaling network
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DOI：
10.15252/msb.20198849
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发表时间：
2019-08-01
影响因子：
9.9
通讯作者：
White, Forest M.
中科院分区：
文献类型：
--
作者：
Dittmann, Antje;Kennedy, Norman J.;White, Forest M.
肥胖相关的2型糖尿病及其伴随疾病已发展成为工业化国家和发展中国家主要的人类健康风险。脂质超载和脂质代谢物如何导致代谢过程放松管制的复杂分子基础尚不完全清楚。我们评估了小鼠在用饱和和不饱和游离脂肪酸处理细胞以及食用高脂肪饮食后的肝脏翻译后改变。这些数据揭示了广泛的酪氨酸磷酸化变化影响了大量参与代谢过程的酶以及典型受体介导的信号转导网络。针对我们数据中两个最显著的受影响的分子特征，src家族激酶活性和活性氧含量升高，显著消除了饱和脂肪暴露在体外和高脂肪饮食在体内的影响。总之，我们提出了饮食诱导酪氨酸信号网络改变的综合观点，包括参与基本代谢途径的蛋白质。
Obesity-associated type 2 diabetes and accompanying diseases have developed into a leading human health risk across industrialized and developing countries. The complex molecular underpinnings of how lipid overload and lipid metabolites lead to the deregulation of metabolic processes are incompletely understood. We assessed hepatic post-translational alterations in response to treatment of cells with saturated and unsaturated free fatty acids and the consumption of a high-fat diet by mice. These data revealed widespread tyrosine phosphorylation changes affecting a large number of enzymes involved in metabolic processes as well as canonical receptor-mediated signal transduction networks. Targeting two of the most prominently affected molecular features in our data, SRC-family kinase activity and elevated reactive oxygen species, significantly abrogated the effects of saturated fat exposure in vitro and high-fat diet in vivo. In summary, we present a comprehensive view of diet-induced alterations of tyrosine signaling networks, including proteins involved in fundamental metabolic pathways.