Hepatic Ceramide May Mediate Brain Insulin Resistance and Neurodegeneration in Type 2 Diabetes and Non-alcoholic Steatohepatitis
Hepatic Ceramide May Mediate Brain Insulin Resistance and Neurodegeneration in Type 2 Diabetes and Non-alcoholic Steatohepatitis
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DOI：
10.3233/jad-2009-0984
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发表时间：
2009-01-01
影响因子：
4
通讯作者：
de la Monte, Suzanne M.
中科院分区：
文献类型：
--
作者：
Lyn-Cook, Lascelles E.;Lawton, Margot;de la Monte, Suzanne M.
肥胖、2型糖尿病（T2 DM）和非酒精性脂肪性肝炎（NASH）可并发认知障碍和神经变性。实验上，高脂饮食（HFD）诱导的肥胖伴T2 DM导致轻度神经退行性变伴脑胰岛素抵抗。由于神经酰胺具有神经毒性，可引起胰岛素抵抗，并且在T2 DM中增加，因此我们研究了神经酰胺作为HFD肥胖/T2 DM模型中神经变性介质的潜在作用。我们用HFD或对照饮食对C57 BL/6小鼠进行配对喂养4-20周，并检查了肝脏和大脑中的前神经酰胺基因表达以及颞叶的神经退行性变。HFD喂养使体重逐渐增加，但16周后，肝脏重量激增（P
Obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic steatohepatitis (NASH) can be complicated by cognitive impairment and neurodegeneration. Experimentally, high fat diet (HFD)-induced obesity with T2DM causes mild neurodegeneration with brain insulin resistance. Since ceramides are neurotoxic, cause insulin resistance, and are increased in T2DM, we investigated the potential role of ceramides as mediators of neurodegeneration in the HFD obesity/T2DM model. We pair-fed C57BL/6 mice with a HFD or control diet for 4-20 weeks and examined pro-ceramide gene expression in liver and brain and neurodegeneration in the temporal lobe. HFD feeding gradually increased body weight, but after 16 weeks, liver weight surged (P