Obesity has become an epidemic in the United States. More than one-third of U.S. adults (35.7%) are obese, and more than one third of children and adolescents are overweight or obese. Obesity affects all organ systems, increasing the incidence of diabetes, cardiovascular disease, cancer, fatty liver disease, and other co-morbidities. Obesity results from an imbalance between energy intake and expenditure. Exploring the role of adipose tissues in regulating energy balance is essential for understanding and treatment of obesity. There are two functionally different types of adipose tissues in mammals: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is the primary site for energy storage, whereas BAT is an adaptive thermogenesis organ that generates heat by energy expenditure. Recent research suggests that energy expenditure induced by active human BAT may play an important role in the adaption to weight loss. BAT activity is significantly higher in lean than obese individuals and the energy expenditure appears to increase in proportion to the amount of BAT activity. Overall, BAT activation is expected to serve as a potential target for obesity interventions. Identification of BAT after cold exposure with 18-Fluoro-deoxyglucose positron emission tomography computed tomography (FDG-PET/CT) imaging by monitoring glucose metabolism led to the discovery of the existence of metabolically active BAT in adult humans. Nevertheless, the utility of FDG-PET/CT for imaging human BAT is limited mainly due to its sensitivity to various body and environmental conditions, lack of tissue characterization in a cellular level and ionizing radiation exposure impeding longitudinal and pediatric studies. Magnetic Resonance Imaging (MRI) provides a non-ionizing radiation imaging modality that is now at the forefront in the assessment of body adipose tissues. Current MRI techniques are focused on differentiation between WAT and BAT;however, there is a lack of the characterization of BAT tissue properties within individuals, and the detection of tissue property changes secondary to BAT activation. Our goal is to develop multi-parametric quantitative MRI methods for BAT tissue characterization and tissue type classification. For the first time, we will implement quantitative MRI BAT imaging in both thermoneutral and cold-stimulated conditions to investigate the BAT microstructural tissue property changes due to cold activation in human. Furthermore, functional blood oxygenation level dependent (BOLD) MRI methods will be developed to investigate the tissue physiological changes in response to acute cold exposure. Cold-stimulated BAT activation map will be generated by both quantitative and functional MRIs. These novel MRI methods will provide information beyond structure and mass to functional measures that may reveal the metabolic and physiological functions of BAT.

Public Health Relevance

We propose to develop novel quantitative and functional magnetic resonance imaging (MRI) methodologies for noninvasive characterization of human brown adipose tissue (BAT) properties and detection of BAT metabolic activity. MRI BAT volume and activity measurements will be compared with the current reference standard - FDG-PET/CT imaging method. The relation between MRI BAT measurements and other clinical indexes (e.g. body-mass-index, metabolic analysis, and body fat composition, etc.) will be investigated in normal-weight and obese subjects. The broad and long-term objectives of our research are to understand the role of BAT in obesity development and to explore the potential of BAT as a target for obesity interventions.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DK103145-01
Application #
8769467
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Laughlin, Maren R
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Children's Memorial Hospital (Chicago)
Department
Type
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60611