Endogenous optical biomarkers of adipose tissue function

 超过30%的美国人肥胖，每年造成的医疗和经济负担接近1470亿美元。有效的抗肥胖干预措施的发展可能会导致肥胖和人类健康的相关方面的显着改善。已经确定了三种不同的脂肪组织（AT）类型。白色（WAT）储库用于能量存储，而棕色（BAT）和米色（BeAT）储库消耗能量以产生热量。因此，导致BeAT/BAT激活流行率提高的方法已成为有希望的抗肥胖干预措施。WAT和BAT具有不同的表型和基因组特性，BAT通常由更广泛的血管网络和具有较小脂滴、致密和更突出的线粒体网络的细胞组成。BeAT在表型和功能上与BAT相似，但主要存在于WAT仓库中。非侵入性成像方法，如PET和扩散光学成像，已被用于检测整个动物和人类中的BAT/BeAT，但缺乏分辨率和对AT类型的特异性;传统的测定是侵入性的。因此，总体目标 该项目的目的是开发微创，因此，潜在的可重复，高分辨率 光学成像方法来识别BAT、WAT和BeAT，以便能够有效开发抗肥胖治疗。本提案的具体目标是识别和验证不同AT及其功能状态的高分辨率内源性荧光和基于散射的定量生物标志物。我们建议评估线粒体光学氧化还原比和组织，脂滴生化和形态学特征，以及血管化作为AT型生物标志物（目的1）在APN动物模型，表现出增加的BeAT库。我们将采用免疫组织化学以及基因和蛋白质表达测定来验证这些光学生物标志物，并且我们将证明它们可用于在细胞水平监测旨在诱导BAT/BeAT激活的产热处理的影响（目标2）。这些研究的预期结果是一组新的AT类型和功能状态的光学生物标志物，可用作有效的抗肥胖干预措施的开发的有力帮助。

 DESCRIPTION (provided by applicant): Over 30% of Americans are obese, creating a medical and economic burden approaching $147 billion annually. The development of effective anti-obesity interventions could lead to significant improvements in obesity and related aspects of human health. Three distinct adipose tissue (AT) types have been identified. White (WAT) depots are used for energy storage, while brown (BAT) and beige (BeAT) depots consume energy to produce heat. Therefore, approaches that lead to enhanced prevalence of activation of BeAT/BAT have emerged as promising anti-obesity interventions. WAT and BAT have distinct phenotypes and genomic identities, with BAT typically consisting of a more extensive vascular network and cells that have smaller lipid droplets, dense and more prominent mitochondrial networks. BeAT is phenotypically and functionally similar to BAT, but is found among predominantly WAT depots. Non-invasive imaging methods, such as PET and diffuse optical imaging, have been used to detect BAT/BeAT in whole animals and humans, but lack in resolution and specificity to AT type; traditional assays are invasive. Thus, the overall objective of this project is to develop minimally invasive, and thus, potentially repeatable, high-resolution optical imaging methods to identify BAT, WAT and BeAT, in order to enable efficient development of anti-obesity treatments. The specific objective of this proposal is the identification and validation of high-resolution endogenous fluorescence and scattering-based quantitative biomarkers of different ATs and their functional state. We propose to assess mitochondrial optical redox ratio and organization, lipid droplet biochemical and morphological characteristics, and vascularization as biomarkers of AT type (Aim 1) in apn animal model that exhibits increased BeAT depots. We will employ immunohistochemical and gene and protein expression assays to validate these optical biomarkers, and we will demonstrate that they can be used to monitor at the cellular level the effects of thermogenic treatment designed to induce BAT/BeAT activation (Aim 2). The expected outcome of these studies is a set of novel optical biomarkers of AT type and functional state that can be used as a powerful aid in the development of effective anti-obesity interventions.