Loss of protein kinase Cbeta function protects mice against diet-induced obesity and development of hepatic steatosis and insulin resistance.
Loss of protein kinase Cbeta function protects mice against diet-induced obesity and development of hepatic steatosis and insulin resistance.
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DOI：
10.1002/hep.22815
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发表时间：
2009-05
期刊：
影响因子：
13.5
通讯作者：
Mehta, Kama D.
中科院分区：
文献类型：
--
作者：
Huang, Wei;Bansode, Rishipal;Mehta, Madhu;Mehta, Kama D.
肥胖是一种能量平衡紊乱，其中摄入量大于支出，大多数多余的热量以甘油三酯（TG）的形式储存。我们以前报道过，缺乏蛋白激酶C（PKCβ）（一种二酰甘油和磷脂依赖性激酶）β亚型的小鼠，表现出全身TG含量显著降低，包括白色脂肪组织（WAT）质量。为了研究这种信号激酶在严重饮食应激的代谢适应中的作用，我们研究了高脂饮食（HFD）对PKCβ表达的影响以及PKCβ缺乏对体重增加的影响。我们现在报告说，HFD选择性增加PKCβ在肥胖倾向的C57 BL/6 J小鼠，特别是在WAT表达;表达水平很少或不变的肝脏，肌肉，肾脏和心脏。肥胖ob/ob小鼠WAT中基础PKCβ表达也升高。值得注意的是，缺乏PKCβ的小鼠对HFD诱导的肥胖有抵抗力，表现出显著降低的WAT和略高的核心体温。与瘦型脂肪营养不良小鼠模型不同，这些小鼠没有脂肪肝或表现出胰岛素抵抗。此外，PKCβ−/−小鼠表现出脂质代谢基因表达的变化，这种变化伴随着血清脂肪因子的显著变化。这些观察结果表明，PKCβ缺乏诱导了一种与肥胖抵抗一致的独特代谢状态，从而提高了PKCβ表达失调可能导致膳食脂肪诱导的肥胖和相关疾病的可能性。
Obesity is an energy balance disorder in which intake is greater than expenditure, with most excess calories stored as triglyceride (TG). We previously reported that mice lacking β-isoform of protein kinase C (PKCβ), a diacylglycerol- and phospholipid-dependent kinase, exhibit marked reduction in the whole body TG content, including white adipose tissue (WAT) mass. To investigate the role of this signaling kinase in metabolic adaptations to severe dietary stress, we studied the impact of a high fat diet (HFD) on PKCβ expression and the effect of PKCβ deficiency on profound weight gain. We now report that HFD selectively increased PKCβ expression in obesity-prone C57BL/6J mice, specifically in WAT; the expression levels were little or unchanged in the liver, muscle, kidney, and heart. Basal PKCβ expression was also found to be elevated in WAT of obese ob/ob mice. Remarkably, mice lacking PKCβ were resistant to HFD-induced obesity showing significantly reduced WAT and slightly higher core body temperatures. Unlike lean lipodystrophic mouse models, these mice did not have fatty livers or exhibited insulin resistance. Moreover, PKCβ−/− mice exhibited changes in lipid metabolism gene expression and such alterations were accompanied by significant changes in serum adipokines. These observations suggest that PKCβ deficiency induced a unique metabolic state congruous with obesity resistance, thus raising the possibility that dysregulation of PKCβ expression could contribute to dietary fat-induced obesity and related disorders.
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影响因子：
4.2
作者：
Jalili, T;Manning, J;Kim, S
通讯作者：
Kim, S
DOI：
10.1152/ajplung.2000.279.3.l429
发表时间：
2000-09-01
影响因子：
4.9
作者：
Dempsey, EC;Newton, AC;Messing, RO
通讯作者：
Messing, RO
影响因子：
7.7
作者：
Bao, S;Kennedy, A;Garvey, WT
通讯作者：
Garvey, WT
影响因子：
5.7
作者：
Guo, Kun;Liu, Yinkun;Chen, Pei
通讯作者：
Chen, Pei
影响因子：
7.7
作者：
Avignon, A;Yamada, K;Farese, RV
通讯作者：
Farese, RV