Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain ; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain.
Mol Metab. 2014 Apr 15;3(4):441-51. doi: 10.1016/j.molmet.2014.04.001. eCollection 2014 Jul.
Krüppel-like factor 4 (KLF4) is a zinc-finger-type transcription factor expressed in a range of tissues that plays multiple functions. We report that hypothalamic KLF4 represents a new transcription factor specifically modulating agouti-related protein (AgRP) expression in vivo. Hypothalamic KLF4 colocalizes with AgRP neurons and is modulated by nutritional status and leptin. Over-expression of KLF4 in the hypothalamic arcuate nucleus (ARC) induces food intake and increases body weight through the specific stimulation of AgRP, as well as blunting leptin sensitivity in lean rats independent of forkhead box protein 01 (FoxO1). Down-regulation of KLF4 in the ARC inhibits fasting-induced food intake in both lean and diet-induced obese (DIO) rats. Silencing KLF4, however, does not, on its own, enhance peripheral leptin sensitivity in DIO rats.
Krüppel 样因子 4（KLF4）是一种在多种组织中表达的锌指型转录因子，具有多种功能。我们报告称，下丘脑 KLF4 是一种新的转录因子，可特异性调节体内的 Agouti 相关蛋白（AgRP）表达。下丘脑 KLF4 与 AgRP 神经元共定位，并受营养状态和瘦素调节。在弓状核（ARC）中过表达 KLF4 会通过特异性刺激 AgRP 引起摄食增加和体重增加，同时独立于叉头框蛋白 01（FoxO1）使瘦素在正常大鼠中的敏感性降低。ARC 中 KLF4 的下调抑制了正常大鼠和饮食诱导肥胖（DIO）大鼠的饥饿诱导摄食。然而，单独沉默 KLF4 并不能增强 DIO 大鼠的外周瘦素敏感性。
