ATP-Sensitive Potassium Channel-Deficient Mice Show Hyperphagia but Are Resistant to Obesity
ATP-Sensitive Potassium Channel-Deficient Mice Show Hyperphagia but Are Resistant to Obesity
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ATP 敏感钾通道缺陷小鼠表现出食欲亢进但对肥胖有抵抗力
DOI：
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发表时间：
2011
影响因子：
5.9
通讯作者：
Yong Woon Kim
中科院分区：
文献类型：
--
作者：
Y. B. Park;Y. Choi;S. Park;Jong Yeon Kim;Seong Ho Kim;D. Song;K. Won;Yong Woon Kim
研究背景下丘脑是体重调节的中枢，下丘脑神经元通过ATP敏感钾通道（KATP）感受血糖水平的变化。我们假设下丘脑葡萄糖感知功能的缺失影响食欲和体重的调节。方法比较Kir6.2基因敲除（KO）小鼠和对照C57 BL/6小鼠对葡萄糖负荷和高脂喂养8周的反应，以验证这一假设。结果注射葡萄糖后1h，C57 BL/6小鼠下丘脑神经肽Y（neuropeptide Y，NPY）含量明显降低，而Kir6.2基因敲除小鼠下丘脑神经肽Y含量无明显变化，提示Kir6.2基因敲除小鼠下丘脑对葡萄糖的反应减弱。Kir6.2基因敲除小鼠在进食状态下下下丘脑NPY表达升高，并伴有摄食过多。然而，与C57 BL/6小鼠相比，Kir6.2 KO小鼠的腹膜后脂肪量显著减少。此外，Kir6.2 KO小鼠在高脂肪喂养8周后的体重和内脏脂肪与对照饮食喂养的Kir6.2 KO小鼠没有显著差异，而C57 BL/6小鼠的体重和内脏脂肪量由于高脂肪喂养而升高。结论Kir 6. 2基因敲除小鼠下丘脑对葡萄糖负荷的反应迟钝，下丘脑NPY表达增加，并伴有摄食量增加，内脏脂肪量减少，对饮食诱导的肥胖有抵抗作用。需要进一步的研究来解释这一现象。
Background The hypothalamus, the center for body weight regulation, can sense changes in blood glucose level based on ATP-sensitive potassium (KATP) channels in the hypothalamic neurons. We hypothesized that a lack of glucose sensing in the hypothalamus affects the regulations of appetite and body weight. Methods To evaluate this hypothesis, the responses to glucose loading and high fat feeding for eight weeks were compared in Kir6.2 knock-out (KO) mice and control C57BL/6 mice, because Kir6.2 is a key component of the KATP channel. Results The hypothalamic neuropeptide Y (NPY) analyzed one hour after glucose injection was suppressed in C57BL/6 mice, but not in Kir6.2 KO mice, suggesting a blunted hypothalamic response to glucose in Kir6.2 KO mice. The hypothalamic NPY expression at a fed state was elevated in Kir6.2 KO mice and was accompanied with hyperphagia. However, the retroperitoneal fat mass was markedly decreased in Kir6.2 KO mice compared to that in C57BL/6 mice. Moreover, the body weight and visceral fat following eight weeks of high fat feeding in Kir6.2 KO mice were not significantly different from those in control diet-fed Kir6.2 KO mice, while body weight and visceral fat mass were elevated due to high fat feeding in C57BL/6 mice. Conclusion These results suggested that Kir6.2 KO mice showed a blunted hypothalamic response to glucose loading and elevated hypothalamic NPY expression accompanied with hyperphagia, while visceral fat mass was decreased, suggesting resistance to diet-induced obesity. Further study is needed to explain this phenomenon.
影响因子：
29
作者：
Alekseev AE;Reyes S;Yamada S;Hodgson-Zingman DM;Sattiraju S;Zhu Z;Sierra A;Gerbin M;Coetzee WA;Goldhamer DJ;Terzic A;Zingman LV
通讯作者：
Zingman LV
影响因子：
2.5
作者：
Jo, Young-Hwan;Su, Ya;Chua, Streamson, Jr.
通讯作者：
Chua, Streamson, Jr.