Abstract

ABHD5 is an important lipase-activating protein, but how it functions to control lipolysis is poorly understood. Screening of the NIH compound library identified compounds that directly bind and activate ABHD5 independently of known extracellular signaling pathways. By using these probes in molecular imaging assays, we discovered endogenous ligands that bind ABDH5 and regulate its lipase-promoting activity. This proposal will investigate this novel locus of lipolysis control using integrated cellular and molecular approaches. A greater understanding of how these endogenous and synthetic compounds regulate ABHD5 could lead to novel therapeutics for treatment of obesity-related disorders.

Public Health Relevance

This project will investigate how proteins regulate intracellular lipolysis. We have identified a novel mechanism for regulating lipolysis in fat and muscle. We have identified endogenous and synthetic chemicals that can activate or inhibit a specific lipase-activating protein. We will determine the cellular consequences of modulating this pathway, and determine how these chemical signals work at a molecular level. The long-term goal is discover novel targets 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 #
5R01DK076629-11
Application #
9906053
Study Section
Cellular Aspects of Diabetes and Obesity Study Section (CADO)
Program Officer
Haft, Carol R
Project Start
2009-06-01
Project End
2021-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
11
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

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

  Publications

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

Showing the most recent 10 out of 24 publications