White adipose tissue (WAT) remodeling is an emerging therapeutic strategy for treatment of obesity-related disorders like diabetes. Remodeling of WAT by beta3 adrenergic activation is a robust model that allows mechanisms to be tested in vivo and in vitro. Using this model system, the progenitors of the brown adipocytes that appear in WAT were identified, and techniques for imaging, isolating, and genetically manipulating these cells in vivo were developed. These cells appear to act as adult 'remodeling stem cells'(rmSC) that are likely involved in the remodeling and cellular restoration of WAT under various conditions. This project will examine mechanisms by which these novel rmSC are recruited by WAT therapeutic remodeling and by chronic high fat feeding. The long term goal is to guide strategies for expanding metabolically desirable adipocyte phenotypes for treating obesity-related disorders.

Public Health Relevance

This project will examine mechanisms by which novel adult stem cells in white adipose tissue are recruited by therapeutic remodeling and by chronic high fat feeding. The long term goal is to guide strategies for expanding metabolically desirable adipocyte phenotypes for treating obesity-related disorders.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01DK062292-10
Application #
8688749
Study Section
Cellular Aspects of Diabetes and Obesity Study Section (CADO)
Program Officer
Haft, Carol R
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Wayne State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
Lee, Yun-Hee; Mottillo, Emilio P; Granneman, James G (2014) Adipose tissue plasticity from WAT to BAT and in between. Biochim Biophys Acta 1842:358-69
Lee, Yun-Hee; Thacker, Robert I; Hall, Brian Eric et al. (2014) Exploring the activated adipogenic niche: interactions of macrophages and adipocyte progenitors. Cell Cycle 13:184-90
Contreras, G Andres; Lee, Yun-Hee; Mottillo, Emilio P et al. (2014) Inducible brown adipocytes in subcutaneous inguinal white fat: the role of continuous sympathetic stimulation. Am J Physiol Endocrinol Metab 307:E793-9
Muzik, Otto; Mangner, Thomas J; Leonard, William R et al. (2013) 15O PET measurement of blood flow and oxygen consumption in cold-activated human brown fat. J Nucl Med 54:523-31
Lee, Yun-Hee; Petkova, Anelia P; Granneman, James G (2013) Identification of an adipogenic niche for adipose tissue remodeling and restoration. Cell Metab 18:355-67