Hyperphagia and obesity in Na,K-ATPase α2 subunit-defective mice
Hyperphagia and obesity in Na,K-ATPase α2 subunit-defective mice
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DOI：
10.1038/oby.2005.204
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发表时间：
2005-10-01
期刊：
影响因子：
--
通讯作者：
Ikeda, K
中科院分区：
文献类型：
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作者：
Kawakami, K;Onaka, T;Ikeda, K
目的：Na，K-ATP酶α 2亚基基因（Atp 1a 2）在脑、骨骼肌、心脏和脂肪细胞中表达。α 2亚基的特殊功能，如参与脂肪细胞的分化和功能，尚未得到解决。本研究的目的是检查是否Atp 1a 2缺陷的杂合子小鼠表现出肥胖症，并揭示肥胖症的潜在机制。研究方法和程序：我们测量了体外分化的脂肪细胞的分化和葡萄糖摄取功能的胚胎成纤维细胞Atp 1a 2缺陷的小鼠。结果：Atp 1a 2杂合子雌性小鼠在中年以后发生肥胖，肥胖小鼠的体重、体重、代谢率、自发活动和神经肽基因mRNA水平均高于野生型小鼠。从野生型，杂合子和纯合子小鼠分离的胚胎成纤维细胞体外脂肪细胞分化的时间过程是没有区别的，葡萄糖和Rb摄取活动的体外分化的脂肪细胞没有改变，胰岛素对葡萄糖摄取的影响和莫能菌素和哇巴因对Rb摄取的基因型之间是相似的。然而，在24小时黑暗-光照周期中，杂合子小鼠在光照期的食物摄入量显著高于野生型小鼠，而在恒定光照条件下则相似。体温，代谢率在休息，和自发运动活动的杂合子小鼠与野生型相似。Orexin mRNA水平在杂合子比野生型mice.Discussion：Na，K-ATP酶α 2亚基不参与体外分化的脂肪细胞的分化或葡萄糖和Rb摄取功能。在Atp 1a 2杂合子小鼠中，暴食可能是肥胖的主要原因。
Objective: The Na,K-ATPase alpha 2 subunit gene (Atp1a2) is expressed in the brain, skeletal muscles, heart, and adipocytes. Specific function of the a2 subunit, such as involvement in differentiation and function of adipocytes, has not been addressed. The aim of this study was to examine whether Atp1a2-defective heterozygous mice show obesity and reveal the mechanisms underlying the obesity.Research Methods and Procedures: We measured the differentiation and glucose uptake function of in vitro-differentiated adipocytes derived from embryonic fibroblasts of Atp1a2-defective mice. Food intake, body temperature, metabolic rate, and spontaneous activity and mRNA levels of neuropeptide genes were compared between the heterozygous and wild-type adult mice.Results: Atp1a2 heterozygous female mice developed obesity after middle age. The time course of in vitro adipocyte differentiation of embryonic fibroblasts isolated from wild type, heterozygous, and homozygous mice was not different, glucose and Rb uptake activities of the in vitro-differentiated adipocytes were not altered, and the effects of insulin on glucose uptake and those of monensin and ouabain on Rb uptake were similar among the genotypes. However, food intake in the light phase was significantly greater in the heterozygous mice than the wild type in the 24-hour dark-light cycle, whereas it was similar under constant-light condition. Body temperature, metabolic rate at rest, and spontaneous motor activity of the heterozygous mice were similar to those of the wild type. Orexin mRNA level was lower in heterozygous than wild-type mice.Discussion: The Na,K-ATPase alpha 2 subunit is not involved in the differentiation or in glucose and Rb uptake function of in vitro-differentiated adipocytes. Hyperphagia is the likely primary cause of obesity in Atp1a2 heterozygous mice.