Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK062292-09
Application #
8485588
Study Section
Cellular Aspects of Diabetes and Obesity Study Section (CADO)
Program Officer
Haft, Carol R
Project Start
2002-07-01
Project End
2017-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
9
Fiscal Year
2013
Total Cost
$319,030
Indirect Cost
$109,142

  Institution

Name
Wayne State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202

  Publications

Burl, Rayanne B; Ramseyer, Vanesa D; Rondini, Elizabeth A et al. (2018) Deconstructing Adipogenesis Induced by ?3-Adrenergic Receptor Activation with Single-Cell Expression Profiling. Cell Metab 28:300-309.e4
Muzik, Otto; Mangner, Tom J; Leonard, William R et al. (2017) Sympathetic Innervation of Cold-Activated Brown and White Fat in Lean Young Adults. J Nucl Med 58:799-806
Lee, Yun-Hee; Kim, Sang-Nam; Kwon, Hyun-Jung et al. (2017) Metabolic heterogeneity of activated beige/brite adipocytes in inguinal adipose tissue. Sci Rep 7:39794
Sanders, Matthew A; Zhang, Huamei; Mladenovic, Ljiljana et al. (2017) Molecular Basis of ABHD5 Lipolysis Activation. Sci Rep 7:42589
Granneman, James G; Kimler, Vickie A; Zhang, Huamei et al. (2017) Lipid droplet biology and evolution illuminated by the characterization of a novel perilipin in teleost fish. Elife 6:
Lee, Yun-Hee; Kim, Sang-Nam; Kwon, Hyun-Jung et al. (2016) Adipogenic role of alternatively activated macrophages in ?-adrenergic remodeling of white adipose tissue. Am J Physiol Regul Integr Comp Physiol 310:R55-65
Gartung, Allison; Zhao, Jiawei; Chen, Simon et al. (2016) Characterization of Eicosanoids Produced by Adipocyte Lipolysis: IMPLICATION OF CYCLOOXYGENASE-2 IN ADIPOSE INFLAMMATION. J Biol Chem 291:16001-10
Ramseyer, Vanesa D; Granneman, James G (2016) Adrenergic regulation of cellular plasticity in brown, beige/brite and white adipose tissues. Adipocyte 5:119-29
Sanders, Matthew A; Madoux, Franck; Mladenovic, Ljiljana et al. (2015) Endogenous and Synthetic ABHD5 Ligands Regulate ABHD5-Perilipin Interactions and Lipolysis in Fat and Muscle. Cell Metab 22:851-60
Lee, Yun-Hee; Petkova, Anelia P; Konkar, Anish A et al. (2015) Cellular origins of cold-induced brown adipocytes in adult mice. FASEB J 29:286-99

Showing the most recent 10 out of 29 publications