Diet-induced obesity resistance of Kv1.3-/- mice is olfactory bulb dependent.

Diet-induced obesity resistance of Kv1.3-/- mice is olfactory bulb dependent.
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DOI:
10.1111/j.1365-2826.2012.02314.x
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发表时间:
2012-08
影响因子:
3.2
通讯作者:
Fadool DA
Fadool DA
中科院分区:
医学3区
文献类型:
--
作者:
Tucker K;Overton JM;Fadool DA

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基因靶向缺失电压门控钾通道Kv1.3(Kv1.3−/−),可提高小鼠的嗅觉敏感度和辨别能力,并导致对饮食诱导肥胖的抵抗。本研究的目的是确定Kv1.3−/−小鼠的嗅觉能力增强是否与其对脱氧核糖核酸的抗性有关。Kv1.3+/+和Kv1.3−/−小鼠在9周龄时接受双侧嗅球切除或假手术,并给予对照饲料(CF)或32%中等高脂饲料(MHF)。在饮食治疗5周后,监测卡路里和水的摄入量、运动活动和氧气消耗。在26周的饮食治疗结束时,评估脂肪垫重量和血液化学。Kv1.3+/+小鼠的体重、肥胖、空腹血糖和空腹瘦素对MHF饮食的反应显著增加,无论是否有OBX。当使用MHF饮食时,Kv1.3−/−小鼠的体重显著低于Kv1.3+/+小鼠,并且表现出显著的光相代谢增加。Kv1.3−/−小鼠的OBX抑制了对DIO的抵抗和伴随的光相代谢的上调,同时减少了暗相代谢和总能量消耗。这些发现表明,在Kv1.3−/−中激活的增加能量消耗并导致对DIO抵抗的通路是嗅球依赖的。因此,这些发现增加了越来越多的证据表明,嗅觉系统可以调节参与能量平衡调节的途径。
Gene-targeted deletion of the voltage-gated potassium channel, Kv1.3 (Kv1.3−/−), increases olfactory sensitivity and discriminatory ability, and causes resistance to diet-induced obesity (DIO) in mice. The objective of the present study was to determine if the enhanced olfactory ability of the Kv1.3−/− mouse contributes to the resistance to DIO. Kv1.3+/+ and Kv1.3−/− mice were subject to bilateral olfactory bulbectomy (OBX) or sham surgery at 9 weeks of age and placed on either a control chow diet (CF) or a 32% moderately high-fat diet (MHF). Caloric and water intake, locomotor activity, and oxygen consumption were monitored after 5 weeks of diet treatment. At the end of 26 weeks of diet treatment, fat pad weight and blood chemistry were evaluated. Kv1.3+/+ mice exhibited a significant increase in weight, adiposity, fasting glucose and fasting leptin in response to the MHF-diet, with or without OBX. When treated with a MHF-diet, Kv1.3−/− mice gained significantly less weight than Kv1.3 +/+ mice and exhibited a significant increase in light phase metabolism. OBX of Kv1.3−/− mice prevented the resistance to DIO and concomitant upregulation of light phase metabolism while decreasing dark phase metabolism and total energy expenditure. These findings suggest that pathways activated in Kv1.3 −/− that increased energy expenditure and led to resistance to DIO are olfactory bulb dependent. Thus, these findings add to a growing body of evidence suggesting that the olfactory system can modulate pathways involved in the regulation of energy balance.
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