Kim Jae Geun, Nam-Goong Il Seong, Yun Chang Ho, Jeong Jin Kwon, Kim Eun Sook, Park Joong Jean, Lee Young Chul, Kim Young Il, Lee Byung Ju
Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan 680-749, South Korea.
Biochem Biophys Res Commun. 2006 Oct 27;349(3):969-75. doi: 10.1016/j.bbrc.2006.08.147. Epub 2006 Sep 1.
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.
TTF-1是同源结构域基因NKx家族的成员，是形态发生和胎儿间脑发育所必需的。我们之前的研究表明，TTF-1在出生后大鼠大脑的某些区域持续表达，并反式激活几种神经肽的基因表达。在本研究中，确定了TTF-1在调节摄食行为中的潜在作用。免疫组织化学分析表明，TTF-1存在于成年大鼠大脑中参与摄食行为控制的几个下丘脑核中。禁食两天显著增加了下丘脑TTF-1 mRNA和蛋白质的水平。脑室内注射反义TTF-1寡脱氧核苷酸显著降低了下丘脑中TTF-1蛋白的丰度。TTF-1减少后，神经肽Y mRNA含量显著降低，阿黑皮素原mRNA含量增加，进而导致动物食物摄入量和体重下降。这些结果表明TTF-1在大鼠下丘脑摄食行为调节中具有新的作用。
