Brain Apolipoprotein AIV, Food Intake and Obesity

载脂蛋白AIV(Apo AIV)是肠道细胞对脂肪摄取的反应而释放的循环信号， 它有助于脂肪餐的厌食作用。我们已经证明了apo AIV也是 在下丘脑合成，下丘脑apo AIV基因表达受到调控 生理上的。我们的长期目标是了解下丘脑载脂蛋白AIV在发育中的作用。 以及如何为预防和治疗目的而对其进行调节。这样做的目的是 应用是评估三个假说。1)当下丘脑apo AIV功能降低时，膳食大小为 慢性增加和肥胖的发展。因此，肥胖的动物会有较低的下丘脑载脂蛋白 与瘦肉动物相比，AIV水平和/或下丘脑ApoAIV对膳食脂肪的反应性较低。2) 外周ApoAIV通过血脑屏障(BBB)参与ApoAIV的中枢作用。 因此，血脑屏障转运受损可能导致下丘脑载脂蛋白AIV水平和作用的降低。 在肥胖的动物身上。3)下丘脑载脂蛋白AIV与其他调节神经肽相互作用，发挥其功能 生理功能。这些假设将根据以下三个具体目标进行评估：1) 测定下丘脑apo AIV基因表达和蛋白水平及下丘脑反应性 ApoAIV对几种品系的肥胖和瘦肉动物的饮食脂质的影响。我们将进一步确定 载脂蛋白AIV基因敲除小鼠对长期高脂喂养的反应。2)研究载脂蛋白AIV的转运 从血液进入中枢神经系统(CNS)，并评估大脑中由 Apo AIV可以中心注射或静脉注射。3)确定载脂蛋白AIV与其他病毒的相互作用 下丘脑内的调节肽。拟议的工作具有创新性，因为它解决了 重要的悬而未决的问题。此外，拟议的研究还利用了 实验方法和几种独特的动物模型。最后，研究结果将是 意义重大，因为预计这些研究将有助于更广泛地理解 载脂蛋白AIV在调节能量稳态中的作用。这一新知识可能会导致新的目标 对日益增长的肥胖症患者特别重要的预防和治疗干预措施 这个国家的人。

Apolipoprotein AIV (apo AIV) is a circulating signal released from intestinal cells in response to lipid feeding, and it contributes to the anorectic effect of a lipid meal. We have demonstrated that apo AIV is also synthesized in the hypothalamus, and that hypothalamic apo AIV gene expression is regulated physiologically. Our long-range goal is to understand the role of hypothalamic apo AIV in the development of obesity and how it can be modulated for preventive and therapeutic purposes. The objective of this application is to evaluate three hypotheses. 1) When hypothalamic apo AIV function is reduced, meal size is chronically increased and obesity develops. Obese animals will, therefore, have lower hypothalamic apo AIV levels and/or lower responsivity of hypothalamic apo AIV to dietary lipids relative to lean animals. 2) Peripheral apo AIV contributes to the central action of apo AIV after crossing the blood-brain barrier (BBB). Therefore, impaired transport across the BBB may result in reduced hypothalamic apo AIV levels and action in obese animals. 3) Hypothalamic apo AIV interacts with other regulatory neuropeptides to exert its physiological function. These hypotheses will be evaluated with the following three specific aims: 1) To determine hypothalamic apo AIV gene expression and protein levels and the responsivity of hypothalamic apo AIV to dietary lipids in several strains of obese and lean animals. We will further determine the response to chronic high-fat feeding in apo AIV knockout mice. 2) To characterize the transport of apo AIV from blood into the central nervous system (CNS) and to assess the areas in the brain that are activated by apo AIV administered either centrally or intravenously. 3) To determine the interaction of apo AIV with other regulatory peptides within the hypothalamus. The proposed work is innovative because it addresses important unanswered questions. In addition, the proposed research takes advantage of the availability of experimental methods and several unique animal models. Finally, the outcomes of the research will be significant because it is expected that these studies will contribute to broader understanding of the role of apo AIV in the regulation of energy homeostasis. This new knowledge may lead to novel targets for preventive and therapeutic interventions that will be particularly important to the growing numbers of obese persons in this country.