TTF-1, a homeodomain-containing transcription factor, regulates feeding behavior in the rat hypothalamus.
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.
Kim
Jae Geun
JG
Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan 680-749, South Korea.
Nam-Goong
Il Seong
IS
Yun
Chang Ho
CH
Jeong
Jin Kwon
JK
Kim
Eun Sook
ES
Park
Joong Jean
JJ
Lee
Young Chul
YC
Kim
Young Il
YI
Lee
Byung Ju
BJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D009478:Neuropeptide Y; C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D011333:Pro-Opiomelanocortin