The overall objective of this EAGER project is to develop a safe and relatively inexpensive multispectral molecular sensing optical technique based on Spatially Offset Diffuse Reflectance Spectroscopy (SODRS), capable of non-invasive, reliable detection of brown fat and measurement of its mass and metabolic activity in humans. Until recently it was believed that adults did not have brown fat and only recent studies performed at Beth Israel Deaconess Medical Center (BIDMC), Joslin Diabetes Center (JDC), Harvard Medical School and at the University of Maastricht, Netherlands show that more than half of adult men and women may have enough brown fat in their bodies to burn off substantial amounts of white fat responsible for obesity. The studies also suggest that brown fat can play an important positive role, since obese people and people with high blood sugar have less brown fat than lean people and people with normal blood sugar. If indeed brown fat is common in adults, then finding ways to promote its activation could provide an important paradigm for preventing or treating obesity, diabetes, and cardiovascular disease. During the proposed one year EAGER pilot project they will develop and build a prototype SODRS molecular sensing instrument capable of detecting brown fat through approximately 1 cm of superficial tissue in humans.
Obesity is currently thought to be the fastest growing health problem in the United States and the primary risk factor for many life threatening diseases such as cardiovascular disease, type 2 diabetes, non-alcoholic fatty liver, and certain types of cancer, such as colon, breast (postmenopausal), endometrial, etc. Recent studies demonstrated the successful treatment of obesity in mice with brown fat activation. In addition, improved glucose tolerance and reduced insulin response during an intravenous glucose tolerance test in mice with activated brown fat, in other words, clear anti-diabetic effects were recently demonstrated. Thus, development of a safe and relatively inexpensive optical technique capable of non-invasive, reliable detection of brown fat and its activation in humans, as developed herein, is extremely important. This project is the first attempt ever to develop a safe non-invasive technique capable of the reliable detection of brown fat and measurement of its mass and metabolic activity in humans. There are enormous difficulties associated with studying human brown fat. PET-CT imaging is currently the only in vivo technology available to monitor it, but PET-CT instruments are rare and very expensive. Moreover, because of radiation exposure, it is not possible to do repeated studies in an individual under various conditions. In this project, the first application of diffuse reflectance spectroscopy to brown fat detection is explored. This radically different approach may provide an important paradigm for preventing or treating obesity and related comorbidities, such as diabetes, cancer and cardiovascular disease. As part of the project, we have developed an optical spectroscopic instrument that is capable of identifying the presence of brown fat in living laboratory mice non-invasively and without the use of any contrast agents. We have further demonstrated that the instrument can measure brown fat activation by commonly utilized short-term cold exposure brown fat activation methods. The proof of concept in vivo measurement of brown fat and its activity represents an important step toward developing a tool for battling the large number of obesity-related health problems.
