Attenuation of age-related metabolic dysfunction in mice with a targeted disruption of the Cbeta subunit of protein kinase A.
Attenuation of age-related metabolic dysfunction in mice with a targeted disruption of the Cbeta subunit of protein kinase A.
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DOI：
10.1093/gerona/glp133
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发表时间：
2009-12
期刊：
影响因子：
--
通讯作者：
Ladiges WC
中科院分区：
文献类型：
--
作者：
Enns LC;Morton JF;Mangalindan RS;McKnight GS;Schwartz MW;Kaeberlein MR;Kennedy BK;Rabinovitch PS;Ladiges WC
环腺苷单磷酸依赖蛋白激酶A （PKA）途径有助于调节细胞生长和分裂，以及甘油三酯的储存和代谢，以响应营养状况。对酵母的研究表明，破坏这一途径能以类似于限制热量的方式促进长寿。由于PKA高度保守，可以在哺乳动物系统中进行研究。本报告描述了缺乏PKA催化亚基Cβ的小鼠的代谢表型。我们证实Cβ在大脑中有高水平的表达，但在肝脏中也有中等水平的表达。c β缺失的动物在喂食标准啮齿动物食物时表现正常，但基础PKA活性降低。然而，缺乏Cβ保护小鼠免受饮食诱导的肥胖、脂肪变性、脂蛋白异常血症和胰岛素抵抗，而热量摄入或运动活动没有任何差异。这些发现具有相关的药理学意义，因为哺乳动物衰老的特征是与肥胖、体脂分布改变和胰岛素抵抗相关的代谢下降。
The cyclic adenosine monophosphate–dependent protein kinase A (PKA) pathway helps regulate both cell growth and division, and triglyceride storage and metabolism in response to nutrient status. Studies in yeast show that disruption of this pathway promotes longevity in a manner similar to caloric restriction. Because PKA is highly conserved, it can be studied in mammalian systems. This report describes the metabolic phenotype of mice lacking the PKA catalytic subunit Cβ. We confirmed that Cβ has high levels of expression in the brain but also showed moderate levels in liver. Cβ-null animals had reduced basal PKA activity while appearing overtly normal when fed standard rodent chow. However, the absence of Cβ protected mice from diet-induced obesity, steatosis, dyslipoproteinemia, and insulin resistance, without any differences in caloric intake or locomotor activity. These findings have relevant pharmacological implications because aging in mammals is characterized by metabolic decline associated with obesity, altered body fat distribution, and insulin resistance.
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DOI：
10.1073/pnas.97.12.6433
发表时间：
2000-06-06
影响因子：
11.1
作者：
Desseyn, JL;Burton, KA;McKnight, GS
通讯作者：
McKnight, GS
影响因子：
158.5
作者：
Calle, EE;Thun, MJ;Heath, CW
通讯作者：
Heath, CW
影响因子：
3.7
作者：
Enns LC;Morton JF;Treuting PR;Emond MJ;Wolf NS;Dai DF;McKnight GS;Rabinovitch PS;Ladiges WC
通讯作者：
Ladiges WC
DOI：
10.1073/pnas.0401516101
发表时间：
2004-05-11
影响因子：
11.1
作者：
Iizuka, K;Bruick, RK;Uyeda, K
通讯作者：
Uyeda, K
影响因子：
15.9
作者：
Djouadi, F;Weinheimer, CJ;Kelly, DP
通讯作者：
Kelly, DP