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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Study Section
Cellular Aspects of Diabetes and Obesity Study Section (CADO)
Program Officer
Haft, Carol R
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Wayne State University
Schools of Medicine
United States
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Lee, Yun-Hee; Kim, Sang-Nam; Kwon, Hyun-Jung et al. (2016) Adipogenic role of alternatively activated macrophages in β-adrenergic remodeling of white adipose tissue. Am J Physiol Regul Integr Comp Physiol 310:R55-65
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
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
Mottillo, Emilio P; Paul, George M; Moore, Hsiao-Ping H et al. (2014) Use of fluorescence microscopy to probe intracellular lipolysis. Methods Enzymol 538:263-78
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
Donato, Michele; Xu, Zhonghui; Tomoiaga, Alin et al. (2013) Analysis and correction of crosstalk effects in pathway analysis. Genome Res 23:1885-93

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