Gut-brain axis and the neuroendocrine regulation of energy balance, growth and reproduction in fish

我的研究重点是大脑和肠道产生的激素（内分泌因子）如何调节鱼类的食物摄入、生长和繁殖。食物摄入主要由大脑和肠道产生的内分泌因子调节，而生长和繁殖主要由大脑、垂体和性腺（睾丸/卵巢）产生的因子调节。我之前用金鱼作为研究激素的典型模型，证明了两种肠脑肽胃饥饿素和甘丙肽刺激鱼类的食物摄入和生长激素（调节生长）和黄体生成素（调节繁殖）的分泌。我推测：(1)摄食、生长和繁殖的调节是由肠脑内分泌因素相互联系的；(2)食欲调节肽直接作用于性腺来调节生殖。本提案的总体目标是研究某些内分泌因子如何影响鱼类的摄食、生长和繁殖。在本次资助期间，我将扩大我对胃饥饿素和丙氨酸的生物学作用的研究，并确定另外两种食欲调节因子，丙氨酸样肽（GALP）和多肽YY （PYY）在金鱼体内的结构和功能。将内分泌因子（如GALP， PYY）注入大脑或胃腔，并测定食物摄入量和血液中的GH和LH水平。测定金鱼生殖腺中ghrelin、galanine、GALP和PYY的存在，并研究它们对生殖腺的直接影响。我也建议用遗传上缺乏胃饥饿素的斑马鱼来进一步表征鱼体内胃饥饿素的食欲调节、生长和生殖功能。总的来说，本提案中概述的基础研究结果(i)有望提供新的信息，以提高我们对鱼类食物摄入、生长和繁殖的激素调节的认识；（ii）可能有利于水产养殖，以促进养殖鱼类的生长和繁殖。

The focus of my research is on how hormones (endocrine factors) produced from the brain and gut regulate food intake, growth and reproduction in fish. Food intake is mainly regulated by endocrine factors produced from the brain and gut, while growth and reproduction are regulated by factors produced mainly from the brain, pituitary and gonads (testis/ovary). Using goldfish, a well-characterized model used to study hormones, I have previously shown that two gut-brain peptides ghrelin and galanin stimulates food intake and secretion of growth hormone (GH; regulates growth) and luteinizing hormone (LH; regulates reproduction) secretion in fish. I hypothesize that (i) the regulation of feeding, growth and reproduction are interlinked by gut-brain endocrine factors and (ii) the appetite regulatory peptides act directly on the gonads to regulate reproduction. The overall objective of this proposal is to study how certain endocrine factors integrate food intake, growth and reproduction in fish. During the term of this grant, I will expand my studies on the biological actions of ghrelin and galanin and identify the structure and functions of two other appetite regulatory factors, galanin like peptide (GALP) and peptide YY (PYY) in goldfish. Endocrine factors (eg: GALP, PYY) will be administered into the brain or into the stomach cavity and food intake and GH and LH levels in blood will be determined. Presence of ghrelin, galanin, GALP and PYY in the gonads of goldfish will be determined and their direct effects on gonads will be studied. I also propose to use zebrafish that genetically lack ghrelin to further characterize the appetite regulatory, growth and reproductive functions of ghrelin in fish. Collectively, the results of the fundamental studies outlined in this proposal (i) are expected to provide new information that will improve our knowledge about the hormonal regulation of food intake, growth and reproduction in fish and (ii) could be beneficial in aquaculture to promote growth and reproduction of cultured fish.