The Role of Neuropeptide Y in Fat Deposition in Birds

神经肽Y是一种神经递质，但也作为一种激素影响其他器官，如脂肪组织。它是鸟类和哺乳动物食物摄入的最强烈刺激之一，并促进哺乳动物脂肪储存。目前还没有关于NPY在鸟类脂肪沉积中的作用的信息，鸟类脂肪积累的控制机制也尚不清楚。增加鸟类和哺乳动物的季节性食物摄入和脂肪积累（例如，分别为迁徙和冬眠做准备）对生存很重要。因此，对脂肪发育的更深入的了解应该为身体成分的季节性变化的进化适应提供新的见解。根据来自瘦鸟和胖鸟的初步数据显示，脂肪组织中NPY和受体基因表达的差异以及对NPY的不同食物摄入反应，我们假设NPY会影响鸟类脂肪的形成和维持，这些过程将受到外源性和脂肪源性NPY的影响。对与鸟类脂肪沉积相关的生理过程的更深入了解，可以广泛应用于所有种类的脊椎动物，这些脊椎动物通过调节食欲和脂肪中的能量储存来周期性适应食物短缺。这些发现也可能有助于肥胖研究，并有可能降低医疗成本。本研究以鸡为模型生物，主要有四个目标：1)通过量化脂肪组织和下丘脑中NPY及其受体的丰度来表征鸟类脂肪-下丘脑NPY轴。2)了解NPY在调节脂肪细胞发育中的作用。方法包括在体外脂肪培养系统中评估NPY治疗对前脂肪细胞增殖和分化的影响。3)确定脂肪源性NPY是否在脂肪形成中起作用。NPY mRNA在前脂肪细胞中被敲低，对分化的影响将被评估。4)阐明NPY对脂肪细胞作用的信号通路。脂肪细胞将被NPY受体亚型特异性拮抗剂处理，以证明NPY影响脂肪的机制。

Neuropeptide Y is a neurotransmitter, but also functions as a hormone to affect other organs such as adipose tissue. It is one of the strongest stimuli of food intake in birds and mammals, and promotes fat storage in mammals. There is no information on the role of NPY in fat deposition in birds and mechanisms governing adipose accumulation in avian species are still unclear. Increased seasonal food intake and fat accumulation in birds and mammals (e.g., in preparation for migration and hibernation, respectively) are important for survival. Thus, a greater understanding of adipose development should provide novel insight into evolutionary adaptations for seasonal changes in body composition. Based on preliminary data from lean and fat birds showing differences in NPY and receptor gene expression in adipose tissue and differential food intake responses to NPY, it is hypothesized that NPY will affect fat formation and maintenance in birds and that these processes will be affected by both exogenous and adipose-derived NPY. A greater understanding of the physiological processes associated with fat deposition in birds has broad applications to all classes of vertebrates that undergo periodic acclimation to food shortage by adjusting appetite and energy storage in fat. The findings may also contribute to obesity research and potentially reduce healthcare costs.This work has four main goals, using chickens as the model organism: 1) Characterize the avian adipose-hypothalamic NPY axis by quantifying the abundance of NPY and its receptors in adipose tissue and hypothalamus. 2) Understand the function of NPY in regulating development of fat cells. Approaches include evaluating effects of NPY treatment on pre-adipocyte proliferation and differentiation in an in-vitro fat culture system. 3) Determine if adipose-derived NPY plays a role in adipogenesis. NPY mRNA will be knocked-down in pre-adipocytes and effects on differentiation will be evaluated. 4) Elucidate the signaling pathway(s) responsible for NPY's effects on fat cells. Fat cells will be treated with NPY receptor sub-type-specific antagonists to demonstrate the mechanism through which NPY affects fat.