Altered hepatic lipid metabolism contributes to nonalcoholic fatty liver disease in leptin-deficient Ob/Ob mice.
Altered hepatic lipid metabolism contributes to nonalcoholic fatty liver disease in leptin-deficient Ob/Ob mice.
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DOI：
10.1155/2013/296537
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发表时间：
2013
影响因子：
3.3
通讯作者：
Rector RS
中科院分区：
文献类型：
--
作者：
Perfield JW 2nd;Ortinau LC;Pickering RT;Ruebel ML;Meers GM;Rector RS
非酒精性脂肪性肝病（NAFLD）与肥胖、胰岛素抵抗和肝脏脂质代谢异常密切相关；然而，对这些过程的精确调控仍然知之甚少。在这里，我们检测了14周龄瘦素缺乏的Ob/Ob小鼠中参与肝脏氧化和脂肪生成的基因和蛋白质，Ob/Ob是一种常见的肥胖和肝脂肪变性模型。与瘦野生型（WT）小鼠相比，肥胖Ob/Ob小鼠空腹血糖、胰岛素和计算的HOMA-IR增加。与WT小鼠相比，Ob/Ob小鼠的肝脏重量、肝脏甘油三酯（TG）含量和新生脂肪生成标志物（包括乙酰辅酶a羧化酶（ACC）、脂肪酸合成酶（FAS）和硬脂酰辅酶a去饱和酶-1 （SCD-1）的肝脏基因表达和蛋白质含量增加，以及PPARγ和SREBP-1c基因表达升高）也更大。虽然Ob/Ob小鼠肝脏PGC-1α、PPARα和TFAM mRNA水平升高，但与WT动物相比，线粒体功能（β-HAD活性、完全（对CO2）和总线粒体棕榈酸氧化）和线粒体OXPHOS蛋白亚基I、III和V含量显著降低。总之，在瘦素缺乏的Ob/Ob小鼠中，肝脏线粒体含量和功能的降低以及新生脂肪生成的上调有助于肥胖相关的NAFLD。
Nonalcoholic fatty liver disease (NAFLD) is strongly linked to obesity, insulin resistance, and abnormal hepatic lipid metabolism; however, the precise regulation of these processes remains poorly understood. Here we examined genes and proteins involved in hepatic oxidation and lipogenesis in 14-week-old leptin-deficient Ob/Ob mice, a commonly studied model of obesity and hepatic steatosis. Obese Ob/Ob mice had increased fasting glucose, insulin, and calculated HOMA-IR as compared with lean wild-type (WT) mice. Ob/Ob mice also had greater liver weights, hepatic triglyceride (TG) content, and markers of de novo lipogenesis, including increased hepatic gene expression and protein content of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD-1), as well as elevated gene expression of PPARγ and SREBP-1c compared with WT mice. While hepatic mRNA levels for PGC-1α, PPARα, and TFAM were elevated in Ob/Ob mice, measures of mitochondrial function (β-HAD activity and complete (to CO2) and total mitochondrial palmitate oxidation) and mitochondrial OXPHOS protein subunits I, III, and V content were significantly reduced compared with WT animals. In summary, reduced hepatic mitochondrial content and function and an upregulation in de novo lipogenesis contribute to obesity-associated NAFLD in the leptin-deficient Ob/Ob mouse.
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影响因子：
7.1
作者：
Schwarz, JM;Linfoot, P;Aghajanian, K
通讯作者：
Aghajanian, K
影响因子：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
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Hobbs, HH
影响因子：
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London, Roslyn M;George, Jacob
通讯作者：
George, Jacob
影响因子：
13.5
作者：
Garcia-Ruiz, Inmaculada;Rodriguez-Juan, Cristina;Solis-Herruzo, Jose A.
通讯作者：
Solis-Herruzo, Jose A.
影响因子：
4.8
作者：
Shimomura, I;Bashmakov, Y;Horton, JD
通讯作者：
Horton, JD