Function and regulation of Letmd1 in metabolic signaling

修改后的项目摘要/摘要部分 这一短期奖励是为了支持收集初步数据，以便提交一项专注于Letmd1在代谢调节中的作用的常规研究资助。产热棕色脂肪组织(BAT)与人体心脏代谢健康有关。重要的是要了解如何控制BAT的生热作用，因为加强BAT的生热作用可能导致新的治疗干预措施，对健康有切实的好处。我们最近证明，Letmd1选择性地富含在BAT中，并且全局Letmd1基因敲除(KO)小鼠表现出严重的冷诱导产热障碍。在目标1中，我们将对KO小鼠整体组织进行呼吸测量，以确定其对OXPHOS呼吸的影响。在目标2中，我们将确定Letmd1的表达是否在小鼠减肥手术模型中发生改变。在目标3中，我们将测试是否可以检测到Letmd1蛋白磷酸化的变化。在目标4中，我们将建立脂肪特异性的Letmd1KO小鼠模型。这些目标将为提交传统的研究拨款申请奠定可行性。

Modified Project Summary/Abstract Section This short-term award is to support the collection of preliminary data for submission of a conventional research grant that focuses on the role of Letmd1 in metabolic regulation. Thermogenic brown adipose tissue (BAT) has been associated with cardiometabolic health in humans. It is important to understand how BAT thermogenesis is controlled because enhancing BAT thermogenesis could lead to new therapeutic interventions with tangible health benefits. We recently demonstrated that Letmd1 is selectively enriched in BAT and that global Letmd1 knockout (KO) mice exhibit severe impairment of cold-induced thermogenesis. In Aim 1, we will perform respirometry with global KO mouse tissues to determine the effect on OXPHOS respiration. In Aim 2, we will determine if the expression of Letmd1 is altered in a mouse bariatric surgery model. In Aim 3, we will test if changes in Letmd1 protein phosphorylation can be detected. In Aim 4, we will generate a fat-specific Letmd1 KO mouse model. These Aims will establish feasibility for the conventional research grant application to be submitted.