C1q/TNF-related Protein 4 (CTRP4) Is a Unique Secreted Protein with Two Tandem C1q Domains That Functions in the Hypothalamus to Modulate Food Intake and Body Weight
C1q/TNF-related Protein 4 (CTRP4) Is a Unique Secreted Protein with Two Tandem C1q Domains That Functions in the Hypothalamus to Modulate Food Intake and Body Weight
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DOI：
10.1074/jbc.m113.506956
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发表时间：
2014-02-14
影响因子：
4.8
通讯作者：
Wong, G. William
中科院分区：
文献类型：
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作者：
Byerly, Mardi S.;Petersen, Pia S.;Wong, G. William
CTRP 4是C1 q家族的独特成员，具有两个串联的球状C1 q结构域。其生理功能定义不清。在这里，我们表明，CTRP 4是一个进化上保守的，近似34 kDa的分泌蛋白在大脑中表达。在人类、小鼠和斑马鱼的大脑中，CTRP 4的表达在发育早期就开始了，并且在中枢神经系统中广泛存在。神经元，而不是星形胶质细胞，表达和分泌CTRP 4，分泌的蛋白质形成更高级的寡聚复合物。CTRP 4也由外周组织产生并在血液中循环。其血清水平在瘦素缺乏的肥胖（ob/ob）小鼠中升高。功能研究表明，CTRP 4在中枢调节能量代谢。禁食一夜后再进食诱导下丘脑CTRP 4的表达。重组蛋白的中央给药抑制了普通饲料喂养和高脂肪饲料喂养小鼠的食物摄入并改变了全身能量平衡。CTRP 4对食物摄入的抑制与下丘脑中食欲神经肽（Npy和Agrp）基因的表达降低相关。这些结果确立了CTRP 4作为食物摄入和能量平衡的新型营养响应性中枢调节剂。
CTRP4 is a unique member of the C1q family, possessing two tandem globular C1q domains. Its physiological function is poorly defined. Here, we show that CTRP4 is an evolutionarily conserved, approximate to 34-kDa secretory protein expressed in the brain. In human, mouse, and zebrafish brain, CTRP4 expression begins early in development and is widespread in the central nervous system. Neurons, but not astrocytes, express and secrete CTRP4, and secreted proteins form higher-order oligomeric complexes. CTRP4 is also produced by peripheral tissues and circulates in blood. Its serum levels are increased in leptin-deficient obese (ob/ob) mice. Functional studies suggest that CTRP4 acts centrally to modulate energy metabolism. Refeeding following an overnight fast induced the expression of CTRP4 in the hypothalamus. Central administration of recombinant protein suppressed food intake and altered the whole-body energy balance in both chow-fed and high-fat diet-fed mice. Suppression of food intake by CTRP4 is correlated with a decreased expression of orexigenic neuropeptide (Npy and Agrp) genes in the hypothalamus. These results establish CTRP4 as a novel nutrient-responsive central regulator of food intake and energy balance.