Targeted deletion of the Vgf gene indicates that the encoded secretory peptide precursor plays a novel role in the regulation of energy balance
Targeted deletion of the Vgf gene indicates that the encoded secretory peptide precursor plays a novel role in the regulation of energy balance
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DOI：
10.1016/s0896-6273(00)80806-5
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发表时间：
1999-07-01
期刊：
影响因子：
16.2
通讯作者：
Salton, SRJ
中科院分区：
文献类型：
--
作者：
Hahm, S;Mizuno, TM;Salton, SRJ
为了确定VGF的功能，VGF是一种由神经元合成的分泌型多肽，在下丘脑中含量丰富，在大脑中受到电活动、损伤和生物钟的调节，我们建立了缺乏VGF的基因敲除小鼠。纯合子突变是小的、高代谢、高活跃和不育的，显著降低瘦素水平和脂肪储存，改变下丘脑前阿片黑素皮质素(POMC)、神经肽Y(NPY)和刺鼠相关肽(AGRP)的表达。此外，禁食正常小鼠下丘脑弓状核中VGF mRNA的合成也被诱导。因此，血管生长因子在能量平衡的调节中起着关键作用，这表明对瘦肉型血管生长因子突变小鼠的研究可能提供对消耗紊乱的洞察，而且血管生长因子的药理拮抗作用(S)可能构成治疗肥胖症的基础。
To determine the function of VGF, a secreted polypeptide that is synthesized by neurons, is abundant in the hypothalamus, and is regulated in the brain by electrical activity, injury, and the circadian clock, we generated knockout mice lacking Vgf. Homozygous mutants are small, hypermetabolic, hyperactive, and infertile, with markedly reduced leptin levels and fat stores and altered hypothalamic proopiomelanocortin (POMC), neuropeptide Y (NPY), and agouti-related peptide (AGRP) expression. Furthermore, VGF mRNA synthesis is induced in the hypothalamic arcuate nuclei of fasted normal mice. VGF therefore plays a critical role in the regulation of energy homeostasis, suggesting that the study of lean VGF mutant mice may provide insight into wasting disorders and, moreover, that pharmacological antagonism of VGF action(s) might constitute the basis for treatment of obesity.