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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.

SUBMITTER: Imbernon M

PROVIDER: S-EPMC4060210 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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

Imbernon Monica M Sanchez-Rebordelo Estrella E Gallego Rosalia R Gandara Marina M Lear Pamela P Lopez Miguel M Dieguez Carlos C Nogueiras Ruben R

Molecular metabolism 20140415 4

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 t ...[more]

PMID: 24944903

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