title: Hypothalamic KLF4 mediates leptin's effects on food intake via AgRP.
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.
authors.affiliation: 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.
authors.forename: Monica
authors.initials: M
authors.lastname: Imbernon
authors.affiliation: 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.
authors.forename: Estrella
authors.initials: E
authors.lastname: Sanchez-Rebordelo
authors.affiliation: Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Gallego
authors.affiliation: Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Gandara
authors.affiliation: Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain.
authors.forename: Pamela
authors.initials: P
authors.lastname: Lear
authors.affiliation: 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.
authors.forename: Miguel
authors.initials: M
authors.lastname: Lopez
authors.affiliation: 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.
authors.forename: Carlos
authors.initials: C
authors.lastname: Dieguez
authors.affiliation: 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.
authors.forename: Ruben
authors.initials: R
authors.lastname: Nogueiras
keywords: AgRP; Food intake; Leptin