Hypothalamic KLF4 mediates leptin's effects on food intake via AgRP

Monica Imbernon; Estrella Sanchez-Rebordelo; Rosalia Gallego; Marina Gandara; Pamela Lear; Miguel Lopez; Carlos Dieguez; Ruben Nogueiras

doi:10.1016/j.molmet.2014.04.001

Hypothalamic KLF4 mediates leptin's effects on food intake via AgRP

Mol Metab. 2014 Apr 15;3(4):441-51. doi: 10.1016/j.molmet.2014.04.001. eCollection 2014 Jul.

Authors

Monica Imbernon¹, Estrella Sanchez-Rebordelo¹, Rosalia Gallego², Marina Gandara², Pamela Lear³, Miguel Lopez¹, Carlos Dieguez¹, Ruben Nogueiras¹

Affiliations

¹ 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.
² Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain.
³ Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain.

Abstract

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.

Keywords: AgRP; Food intake; Leptin.