Gender-specific effects on food intake but no inhibition of age-related fat accretion in transgenic mice overexpressing human IGFBP-2 lacking the Cardin-Weintraub sequence motif
Gender-specific effects on food intake but no inhibition of age-related fat accretion in transgenic mice overexpressing human IGFBP-2 lacking the Cardin-Weintraub sequence motif
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在过度表达缺乏 Cardin-Weintraub 序列基序的人 IGFBP-2 的转基因小鼠中，性别对食物摄入有特异性影响，但对与年龄相关的脂肪堆积没有抑制作用
DOI：
10.1007/s12079-015-0264-z
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发表时间：
2015
影响因子：
4.1
通讯作者：
Hoeflich A
中科院分区：
文献类型：
--
作者：
Wiedmer P;Schwarz F;Große B;Schindler N;Tuchscherer A;Russo VC;Tschöp MH;Hoeflich A
IGFBP-2影响生长和代谢，被认为通过其肝素结合域(HBD)影响能量平衡和体内脂肪的积累。为了评估存在于连接域(HBD1)中的HBD的功能，我们建立了过表达突变的人IGFBP-2的转基因小鼠，该突变人IGFBP-2缺乏PKKLRP序列，而携带PNNLAP序列。转基因小鼠高表达人IGFBP-2，而内源性IGFBP-2或IGF-I血清浓度不受影响。在两个性别中，我们对生长和新陈代谢进行了纵向分析，包括至少4个独立的时间点，从10岁到52周。通过核磁共振(核磁共振)分析来评估体成分。食物摄入量通过自动在线监测进行记录。我们描述了突变的人胰岛素样生长因子结合蛋白-2对体重、纵向生长和瘦体重的负面影响(p<； 0.05)。很明显，突变的IGFBP-2在一生中没有观察到对脂肪质量增加的负面影响。相反，不同性别的转基因小鼠的相对脂肪质量都增加了(p<； 0.05)。在雄性小鼠中，转基因表达显着增加了所有年龄组的总脂肪的绝对质量(p<； 0.05)。雌性转基因小鼠的摄食量增加，而雄性转基因小鼠在11周大时摄食量减少。因此，我们的研究清楚地提供了HBD1缺陷的hIGFBP-2(H1d-BP-2)对脂肪质量增加和食物摄入量的性别和时间特异性影响。虽然我们的数据与目前关于HB结构域在脂肪增加中的作用的知识基本一致，但我们现在也可能推测HBD1在控制饮食行为方面的作用。
IGFBP-2 affects growth and metabolism and is thought to impact on energy homeostasis and the accretion of body fat via its heparin binding domains (HBD). In order to assess the function of the HBD present in the linker domain (HBD1) we have generated transgenic mice overexpressing mutant human IGFBP-2 lacking the PKKLRP sequence and carrying a PNNLAP sequence instead. Transgenic mice expressed high amounts of human IGFBP-2, while endogenous IGFBP-2 or IGF-I serum concentrations were not affected. In both genders we performed a longitudinal analysis of growth and metabolism including at least 4 separate time points between the age of 10 and 52 weeks. Body composition was assessed by nuclear magnetic resonance (NMR) analysis. Food intake was recorded by an automated online-monitoring. We describe negative effects of mutant human IGFBP-2 on body weight, longitudinal growth and lean body mass (p< 0.05). Very clearly, negative effects of mutant IGFBP-2 were not observed for fat mass accretion throughout life. Instead, relative fat mass was increased in transgenic mice of both genders (p< 0.05). In male mice transgene expression significantly increased absolute mass of total body fat over all age groups (p< 0.05). Food intake was increased in female but decreased in male transgenic mice at an age of 11 weeks. Thus our study clearly provides gender- and time-specific effects of HBD1-deficient hIGFBP-2 (H1d-BP-2) on fat mass accretion and food intake. While our data are in principal agreement with current knowledge on the role of HB-domains for fat accretion we now may also speculate on a role of HBD1 for the control of eating behavior.
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影响因子：
3.7
作者：
Sartorius T;Peter A;Schulz N;Drescher A;Bergheim I;Machann J;Schick F;Siegel-Axel D;Schürmann A;Weigert C;Häring HU;Hennige AM
通讯作者：
Hennige AM
瘦素输注三天后，循环母羊中芳香酶、IGF-I受体、IGF结合蛋白-2、-4和-5、瘦素和瘦素受体的mRNA的卵巢表达。
影响因子：
3.8
作者：
M. Muñoz;P. Findlay;C. Adam;G. Wax;B. Campbell;N. Kendall;M. Khalid;M. Forsberg;R. Scaramuzzi
通讯作者：
R. Scaramuzzi
影响因子：
5.3
作者：
Shen, Xinchun;Xi, Gang;Clemmons, David R.
通讯作者：
Clemmons, David R.
影响因子：
29
作者：
Hedbacker, Kristina;Birsoy, Kivanc;Friedman, Jeffrey M.
通讯作者：
Friedman, Jeffrey M.
影响因子：
4.8
作者：
Takami Arai;W. Busby;D. Clemmons
通讯作者：
Takami Arai;W. Busby;D. Clemmons