纖維母細胞生長因子第一型 (Fibroblast growth factor 1, FGF1)在生物體內扮演著重要的角色，如神經發育與成熟、突觸生長、腫瘤形成和傷口癒合。同時，FGF1也是神經營養因子，在成體腦細胞中廣泛表現。此外，FGF1基因同型合子 (Homozygous)缺陷的小鼠在高油脂飲食下，會產生肥胖、高血壓與糖尿病等症狀，意味著FGF1在代謝平衡中扮演著很重要的角色。然而，FGF1在腦中調控代謝平衡的機制尚未釐清。
我們利用實驗室的客製化FGF1抗體染小鼠腦片，發現FGF1表現在室旁核 (Paraventricular nucleus, PVN)，並且，這些表現FGF1的細胞，也會同時表現成熟神經細胞的標記NeuN。我們因此得知，表現FGF1的細胞是神經細胞。接著，我們也發現FGF1會和調控食物攝取量的催產素 (Oxytocin, Oxt)和Nesfatin-1 (Nesf-1)共同表現。再者，Nesf-1、Oxt和FGF1的表現量皆會在小鼠禁食18小時後下降，並且於再餵食之後上升。因此，我們假設FGF1涉及Nesf-1/Oxt有關的飽足感途徑。我們經由透過第三腦室給予Nesf-1、Oxt、與三種不同的FGF1，這些因子皆會導致小鼠進食量減少。此三種FGF1分別為全長 (FGF1FL)、截短 (Truncated, ΔFGF1) (缺少N端的15個胺基酸)、及FGF12-15 (由第2-15個胺基酸所組成的胜肽)。FGF1FL和ΔFGF1對食慾的抑制效果相似，且較FGF12-15顯著。最後，透過共同注射配體 (Ligand)/拮抗劑 (Antagonist)或配體/抗體，我們證明FGF1的訊息傳遞作用在Oxt的下游。
綜合先前的研究可得知，調控飽足感的訊息傳遞路徑為Nesf-1至Oxt，再傳遞到FGF1。此發現使得我們更加了解Nesf-1的訊息傳遞路徑，並提供未來治療肥胖的可能標的。

Fibroblast growth factor 1 (FGF1) is an important protein that is involved in neuronal development, maturation, neurite outgrowth, tumorigenesis, and wound healing. It also serves as a neurotrophic factor, widely expressed in adult brain cells. In addition, mice with homozygous deficiency of fgf1 gene and fed with high-fat diet resulted in obesity, high blood pressure, and diabetes. These results indicated that FGF1 plays an important role in metabolic homeostasis. However, the FGF1 metabolic pathway in brain remains unknown.
The mouse brain slices were stained with the customized antibody in our lab, and FGF1 was found expressed in paraventricular nuclei, co-expressed with neuronal marker, NeuN. The results demonstrated that FGF1-expressing cells are neurons. Then, we showed that FGF1 co-expressed with oxytocin and nesfatin-1, both are involved in food intake regulation. Next, we found that the levels of nesfatin-1, oxytocin, and FGF1 were reduced when the mice were deprived of food for 18 hours. Further, the levels of these three factors increase after refeeding. We then test the hypothesis that FGF1 is involved in the nesfatin-1/oxytocin-related satiety pathway. Through third ventricle administration of mice with nesfatin-1, oxytocin, and three different FGF1 variants, we confirmed that all of these factors could reduce food intake in mice. The three different FGF1 variants are full-length FGF1 (FGF1FL), truncated FGF1 (lacking the first 15 amino acids, ΔFGF1), and FGF12-15 (a peptide comprising #2-15 amino acids of FGF1). The appetite suppression effects in FGF1FL and ΔFGF1 are similar, while the appetite suppression by FGF12-15 is much less effective than FGF1FL and ΔFGF1. Finally, through the injections of combinations of ligand/antagonist or ligand/antibody, we demonstrated that FGF1 signaling is downstream of oxytocin.
Thus, we conclude that the signaling pathway for satiety is from nesfatin-1 to oxytocin and to FGF1. The findings together provide a better understanding of nesfatin-1 signaling pathway and also offer a new target in devising therapies for obesity treatment.

摘要.......................................I
Abstract...................................III
Table of Contents..........................V
Abbreviation...............................VI
Introduction...............................1
Materials and Methods......................7
Results....................................13
Discussion.................................19
References.................................26
Tables.....................................33
Figures....................................36

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