TTF-1, a homeodomain-containing transcription factor, regulates feeding behavior in the rat hypothalamus

Document Type

Journal Article

Publication Date

10-27-2006

Journal

Biochemical and Biophysical Research Communications

Volume

349

Issue

3

DOI

10.1016/j.bbrc.2006.08.147

Keywords

Food intake; Hypothalamus; Neuropeptide Y; Obesity; Proopiomelanocortin; TTF-1

Abstract

TTF-1 is a member of the NKx family of homeodomain genes, and is required for morphogenesis and fetal diencephalon development. Our previous studies have shown that TTF-1 expression is maintained in some regions of the postnatal rat brain and transactivates the gene expression of several neuropeptides. In this study, a potential role for TTF-1 in the regulation of feeding behavior was identified. Immunohistochemical analysis showed that TTF-1 is present in several hypothalamic nuclei of the adult rat brain involved in the control of feeding behavior. Food deprivation for two days markedly increased the hypothalamic levels of TTF-1 mRNA and protein. Intracerebroventricular administration of an antisense TTF-1 oligodeoxynucleotide significantly decreased TTF-1 protein abundance in the hypothalamus. This TTF-1 decrease was followed by a significant decrease in neuropeptide Y mRNA content and an increase in proopiomelanocortin mRNA content, and in turn resulted in a decrease of the animal's food intake and body weight. These results suggest a novel role for TTF-1 in the regulation of feeding behavior in the rat hypothalamus. © 2006 Elsevier Inc. All rights reserved.

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