TASTE AND GENETIC MECHANISMS OF MACRONUTRIENT SELECTION

该项目的长期目标是为味觉和影响宏量营养素选择的遗传因素之间的联系提供新的证据。该建议的总体假设是，不同小鼠品系对脂肪或碳水化合物来源的不同偏好是由基因决定的，品系对味道偏好的差异有助于这种常量营养素选择行为。用于验证这一假设的主要策略将是研究行为口味偏好和宏量营养素自我选择，共分离分析和遗传连锁分析。最近，我们确定了一个有价值的模型来研究味觉和饮食选择之间的关系：两种新的小鼠品系，它们表现出不同的宏量营养素选择模式。AKR/J和C57BL/6J小鼠对脂肪的选择/消耗比例较高，而SWR/J和CAST/Ei小鼠对碳水化合物的选择/消耗比例较高。AKR/J vs. SWR/J差异巨量营养素选择模型可以推广到许多其他饮食模式，但3选择巨量营养素选择模式已被确定为最准确和可靠的行为表型，可用于本研究计划中描述的遗传分析。此外，初步数据表明，AKR/J和SWR/J小鼠对玉米油乳剂和苦味剂八乙酸蔗糖（SOA）的口味偏好也存在差异。品系味觉反应性差异的鉴定与宏量营养素的选择有关，即有证据表明苦味敏感性的遗传控制，最近的研究表明苦味敏锐度与对脂肪的偏好有关。因此，Specific Aim 1将使用两瓶偏好测试来研究第二对新菌株（C57BL/6J和CAST/Ei）对玉米油和SOA的口味偏好反应。在具体目标2中，将使用F2杂交育种策略（AKR/J x SWR/J和C57BL/6J x CAST/Ei）对行为表型的遗传模式进行遗传分析。两对具有不同的常量营养素选择和口味偏好模式的菌株的可用性也将允许对F2后代进行共分离分析，以确定是否有证据表明脂肪或碳水化合物偏好和苦味敏感性差异的共同遗传机制。然而，这项研究计划最重要的潜在结果是能够定位影响宏量营养素选择行为的基因的染色体位置。因此，在Specific Aim 3中，将使用数量性状位点（QTL）策略对两个F2群体进行全基因组筛选，进行遗传定位研究。这些研究的结果将提供一个新的理解的味道和遗传机制背后的宏量营养素的选择。

The long-term goal of this project is to provide new evidence for a link between taste and genetic factors that influence macronutrient selection. The overall hypothesis of this proposal is that distinct and contrasting preferences for fat or carbohydrate sources across mouse strains are genetically determined and that strain differences in taste preference(s) contribute to this macronutrient selection behavior. The primary strategies used to test this hypothesis will be studies of behavioral taste preference and macronutrient self-selection, cosegregation analysis, and genetic linkage analysis. Recently we identified a valuable model for investigating the relationship between taste and dietary selection: two novel mouse strain pairs that exhibit contrasting patterns of macronutrient selection. AKR/J and C57BL/6J mice select/consume a higher proportion of fat while the SWR/J and CAST/Ei mice select/consume a higher proportion of carbohydrate. The AKR/J vs. SWR/J model of differential macronutrient selection generalizes to many other diet paradigms however the 3-choice macronutrient selection paradigm has been identified as the most accurate and reliable behavioral phenotype to be used in the genetic analyses described in this research plan. Moreover preliminary data indicate that AKR/J and SWR/J mice also differ in their taste preferences for corn oil emulsions and for the bitter tastant sucrose octaacetate (SOA). The identification of strain differences in taste responsiveness is relevant to macronutrient selection, i.e., there is evidence for genetic control of bitter taste sensitivity, and recent studies suggest an association between bitter taste acuity and the preference for fat. Thus Specific Aim 1 will examine the taste preference responses to corn oil and SOA in the second novel strain pair (C57BL/6J and CAST/Ei), using two-bottle preference tests. In Specific Aim 2, a genetic analysis of the mode of inheritance of the behavioral phenotypes will be performed using an F2 intercross breeding strategy (AKR/J x SWR/J and C57BL/6J x CAST/Ei). The availability of two strain pairs with contrasting patterns of macronutrient selection and taste preferences will also permit a cosegregation analysis in the F2 progeny to determine whether there is evidence for a common genetic mechanism underlying differences in fat or carbohydrate preference and bitter taste sensitivity. However the most important potential result of this research plan is the ability to locate the chromosomal positions of genes underlying the macronutrient selection behavior. Thus in Specific Aim 3, a genetic mapping study will be carried out using the quantitative trait loci (QTL) strategy of performing a whole genome screen in two F2 populations. The results of these studies will provide a new understanding of the taste and genetic mechanisms underlying macronutrient selection.