Deficiency of glucose-dependent insulinotropic polypeptide receptor prevents ovariectomy-induced obesity in mice.
Deficiency of glucose-dependent insulinotropic polypeptide receptor prevents ovariectomy-induced obesity in mice.
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葡萄糖依赖性促胰岛素多肽受体的缺乏可预防小鼠卵巢切除引起的肥胖。
DOI：
10.1152/ajpendo.00008.2008
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Weickert,MartinO
中科院分区：
文献类型：
--
作者：
Isken,Frank;Pfeiffer,AndreasFH;Nogueiras,Rubén;Osterhoff,MartinA;Ristow,Michael;Thorens,Bernard;Tschöp,MatthiasH;Weickert,MartinO
更年期和早产性类固醇缺乏与脂肪和体重的增加有关。去卵巢(OVX)的小鼠也表现出运动活动减少。葡萄糖依赖的促胰岛素多肽(GIP)在脂肪代谢和运动活动中都发挥着重要作用。因此，我们假设雌激素对体重、脂肪质量和自发体力活动的调节作用可能部分是通过GIP信号来实现的。为了验证这一假设，C57BL/6小鼠和GIP受体基因敲除小鼠(GIPR−/−)被暴露于去卵巢或假手术(每组10只)。在超过26wk的时间里，观察对所有四组小鼠的身体成分、胰岛素抵抗标志物、能量消耗、运动活动以及下丘脑厌食和食欲因子表达的影响。OVX野生型小鼠如预期的那样出现肥胖、脂肪量增加和胰岛素抵抗标记物升高。在OVX GIPR−/−动物中，这是完全防止的，尽管它们的能量消耗和自发运动活动水平与OVX野生型小鼠没有显著差异。OVX GIPR−/−动物的累积摄食量显著减少，并与下丘脑促食欲素神经肽Y(NPY)的表达显著降低有关，但与可卡因-苯丙胺相关转录物(CART)、黑素皮质素受体(MCR-3和MCR-4)或促甲状腺激素释放激素(TRH)的表达无关。因此，GIP受体在调节小鼠摄食量的下丘脑中与雌激素相互作用，它们的阻断可能在预防性腺类固醇缺乏症的肥胖方面具有很好的潜力。
Menopause and premature gonadal steroid deficiency are associated with increases in fat mass and body weight. Ovariectomized (OVX) mice also show reduced locomotor activity. Glucose-dependent-insulinotropic-polypeptide (GIP) is known to play an important role both in fat metabolism and locomotor activity. Therefore, we hypothesized that the effects of estrogen on the regulation of body weight, fat mass, and spontaneous physical activity could be mediated in part by GIP signaling. To test this hypothesis, C57BL/6 mice and GIP-receptor knockout mice (Gipr−/−) were exposed to OVX or sham operation (n= 10 per group). The effects on body composition, markers of insulin resistance, energy expenditure, locomotor activity, and expression of hypothalamic anorexigenic and orexigenic factors were investigated over 26 wk in all four groups of mice. OVX wild-type mice developed obesity, increased fat mass, and elevated markers of insulin resistance as expected. This was completely prevented in OVX Gipr−/−animals, even though their energy expenditure and spontaneous locomotor activity levels did not significantly differ from those of OVX wild-type mice. Cumulative food intake in OVX Gipr−/−animals was significantly reduced and associated with significantly lower hypothalamic mRNA expression of the orexigenic neuropeptide Y (NPY) but not of cocaine-amphetamine-related transcript (CART), melanocortin receptors (MCR-3 and MCR-4), or thyrotropin-releasing hormone (TRH). GIP receptors thus interact with estrogens in the hypothalamic regulation of food intake in mice, and their blockade may carry promising potential for the prevention of obesity in gonadal steroid deficiency.
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GIP受体拮抗和PYY(3-36)受体激活对高脂喂养小鼠代谢影响的比较
影响因子：
3
作者：
N. Irwin;K. Hunter;P. Flatt
通讯作者：
P. Flatt
影响因子：
2.7
作者：
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胰岛中的 Frataxin 缺乏会因 β 细胞质量的损失而导致糖尿病。
影响因子：
15.9
作者：
M. Ristow;H. Mulder;D. Pomplun;T. Schulz;Katrin Müller;Anja Krause;M. Fex;H. Puccio;Jörg Müller;F. Isken;J. Spranger;D. Müller;M. Magnuson;M. Möhlig;M. Koenig;A. Pfeiffer
通讯作者：
A. Pfeiffer
影响因子：
4.1
作者：
COLVIN, GB;SAWYER, CH
通讯作者：
SAWYER, CH
DOI：
10.1172/jci20518
发表时间：
2004-02
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
F. Preitner;M. Ibberson;I. Franklin;C. Binnert;M. Pende;A. Gjinovci;Tanya Hansotia;D. Drucker;C. Wollheim;R. Burcelin;B. Thorens
通讯作者：
F. Preitner;M. Ibberson;I. Franklin;C. Binnert;M. Pende;A. Gjinovci;Tanya Hansotia;D. Drucker;C. Wollheim;R. Burcelin;B. Thorens