The storage and mobilization of lipids are fundamental cellular processes. In mammals, adipose tissue functions as a specialized lipid buffer that stores excess energy as triglyceride for systemic mobilization as free fatty acids (FFA). Nonetheless, virtually all cells have the ability to store and mobilize FFA;indeed, for some tissues FFA can provide the major source of metabolic energy. Excessive FFA can disrupt cellular function in a process that has been termed 'lipotoxicity,"""""""" which is thought to be a major means by which obesity contributes to diabetes and cardiovascular disease. In theory, lipotoxicity can be brought about by excessive systemic supply of FFA from adipose tissue, or by an imbalance in FFA storage and mobilization in peripheral tissues. Thus, a mechanistic understanding of how cells assimilate, mobilize and channel FFA is an important biological question with broad implications for health and disease. Our long term goal is to provide a mechanistic understanding of cellular lipolysis so as to identify novel points of therapeutic intervention for the treatment of obesity and diabetes. We hypothesize that intracellular lipolysis is controlled by the orderly trafficking of specific proteins at the surface of specialized lipid droplets. This work will define the intracellular sites where lipolysis occurs, test specific models of dynamic protein-protein interactions, and determine the functional impact of those interactions in vitro and in vivo.

Public Health Relevance

The storage and mobilization of lipids are fundamental cellular processes that affect health and disease. This project investigates how cells breakdown stored fat. The long term goal is to identify novel points of therapeutic intervention for the treatment of obesity and diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK076629-04
Application #
8298993
Study Section
Cellular Aspects of Diabetes and Obesity Study Section (CADO)
Program Officer
Haft, Carol R
Project Start
2006-12-01
Project End
2015-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$311,600
Indirect Cost
$106,600
Name
Wayne State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Ramseyer, Vanesa D; Kimler, Victoria A; Granneman, James G (2018) Vacuolar protein sorting 13C is a novel lipid droplet protein that inhibits lipolysis in brown adipocytes. Mol Metab 7:57-70
Goldberg, Ira J; Reue, Karen; Abumrad, Nada A et al. (2018) Deciphering the Role of Lipid Droplets in Cardiovascular Disease: A Report From the 2017 National Heart, Lung, and Blood Institute Workshop. Circulation 138:305-315
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
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
Granneman, J G (2015) Renaissance of brown adipose tissue research: integrating the old and new. Int J Obes Suppl 5:S7-S10

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