Endogenous optical biomarkers of adipose tissue function

脂肪组织功能的内源性光学生物标志物

基本信息

批准号：
9052761
负责人：
IRENE GEORGAKOUDI
金额：
$ 17.08万
依托单位：
TUFTS UNIVERSITY MEDFORD
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-15 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9052761
关键词：
Adipose tissue Adult Adverse effects Algorithms American Animal Model Animals Biochemical Biological Assay Biological Markers Blood Vessels Burn injury Cardiovascular Diseases Cells Cellular Metabolic Process Characteristics Child Consumption Corticotropin-Releasing Hormone Data Development Diabetes Mellitus Diffuse Economic Burden Endogenous Factors Engineering Exhibits Fatty acid glycerol esters Fluorescence Functional disorder Gene Expression Genomics Health Heating Histocompatibility Testing Human Human body Image Image Analysis In Vitro Inflammation Intervention Knockout Mice Knowledge Lead Life Lipids Mammals Measurement Mediating Medical Economics Metabolic Methodology Mitochondria Modeling Monitor Mus Obesity Optics Outcome Study Oxidation-Reduction Pathway interactions Pharmaceutical Preparations Phenotype Physiology Plant Roots Play Positron-Emission Tomography Preclinical Drug Evaluation Prevalence Property Proteomics Reading Resolution Rodent Specificity Stimulus Testing Time Tissues Validation Vascularization base fluorescence imaging imaging modality in vivo in vivo imaging innovation microscopic imaging minimally invasive mouse model non-invasive imaging novel obesity treatment optical imaging potential biomarker prevent protein expression response spectrograph stressor subcutaneous therapy design tissue biomarkers tool two-photon

项目摘要

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.

描述（由适用提供）：超过30％的美国人肥胖，每年造成1470亿美元的医疗和经济燃烧。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）沉积物用于储能，而棕色（BAT）和米色（Beat）沉积物会消耗能量产生热量。因此，导致节拍/蝙蝠激活患病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身份，BAT通常由更广泛的血管网络和细胞组成，这些细胞具有较小的脂质液滴，密集且更为突出的线粒体网络。 BEAT在表型和功能上与BAT相似，但在主要的WAT沉积物中被发现。非侵入性成像方法（例如PET和弥漫性光学成像）已被用来检测全动物和人类中的蝙蝠/节拍，但缺乏分辨率和类型的特异性。传统测定是侵入性的。那是总体目标。该项目的最小化，因此可能重复，高分辨率光学成像方法识别蝙蝠，WAT和BEAT，以便有效发展抗肥胖治疗。该建议的具体目标是对不同ATS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的识别和验证。我们建议将线粒体光学氧化还原比和组织，脂质液滴生化和形态学特征以及血管化评估为APN动物模型中AT类型的生物标志物（AIM 1），表现出增加的节拍沉积物。我们将采用免疫组织化学和基因和蛋白质表达测定法来验证这些光学生物标志物，我们将证明它们可用于在细胞水平上监测旨在诱导蝙蝠/跳动激活的热治疗的影响（AIM 2）。这些研究的预期结果是一组新型的AT类型和功能状态的光学生物标志物，可以用作有效的抗肥胖干预措施的强大帮助。