Our Program Project Grant (PPG), "New Molecules in Triglyceride Metabolism and Adipogenesis," is guided by a unifying theme-to understand mechanisms for triglyceride delivery to peripheral tissues, triglyceride synthesis, and adipogenesis. The topic of this PPG is highly relevant to obesity and hyperlipidemia, two public health problems that are central to the mission of the NHLBI. Working as a team over the past 5 years, the Project and Core Leaders of this PPG have studied new molecules with crucial roles in triglyceride delivery to cells, triglyceride synthesis within cells, and adipogenesis. These studies identified new regulators of lipid metabolism and adipogenesis and have uncovered new causes of human disease. For the next 5 years, our PPG team will be guided by the same objective-to understand the mechanisms underlying obesity and metabolic disease. This PPG is organized into three Component Projects and two Cores. Project 1, "Function of GPIHBP1 in Triglyceride Metabolism," will be led by Dr. Stephen G. Young. This project focuses on a novel endothelial cell protein, GPIHBP1, and its role in plasma triglyceride metabolism and the delivery of lipid nutrients to adipose tissue, heart, and skeletal muscle. Project 2, "Lipin Protein Family Interactions, Lipid Intermediates, and Disease," will be led by Dr Karen Reue. Dr. Reue's discovery of the lipin family of enzymes set the stage for new studies on the regulation of triglyceride synthesis and the control of adipogenesis. Project 3, "Novel Pathways for Triglyceride Storage and Adipogenesis," will be led by Dr. Peter Tontonoz. Dr. Tontonoz identified new molecules controlling lipid metabolism and adipogenesis, including TLE3 and IDOL (inducible degrader of the LDL receptor). Dr. Tontonoz will decipher mechanisms by which these new players in lipid metabolism affect adipogenesis. A "Mouse Model and Protein Expression Core" (Core A) will create new lines of genetically modified mice and will produce purified proteins for biochemical studies and antibody production. An "Administrative" Core (Core B) will facilitate the efforts by all three Component Projects, organize advisory board meetings, and ensure compliance with institutional and NIH guidelines.

Public Health Relevance

Our country faces an epidemic of hyperlipidemia, metabolic disease, and obesity-exacting a horrific toll on patients, families, and our nation's health care budget. The guiding objective for this PPG is to understand the molecular mechanisms that govern fuel delivery to cells, hyperlipidemia, triglyceride synthesis, and adipogenesis. Pursuing this objective should lead to new treatments for metabolic disease and obesity.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Study Section
Special Emphasis Panel (ZHL1-PPG-R (O1))
Program Officer
Ershow, Abby
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University of California Los Angeles
Internal Medicine/Medicine
Schools of Medicine
Los Angeles
United States
Zip Code
Arnold, Arthur P; Reue, Karen; Eghbali, Mansoureh et al. (2016) The importance of having two X chromosomes. Philos Trans R Soc Lond B Biol Sci 371:20150113
Tian, Xiao Yu; Ganeshan, Kirthana; Hong, Cynthia et al. (2016) Thermoneutral Housing Accelerates Metabolic Inflammation to Potentiate Atherosclerosis but Not Insulin Resistance. Cell Metab 23:165-78
Wang, Bo; Rong, Xin; Duerr, Mark A et al. (2016) Intestinal Phospholipid Remodeling Is Required for Dietary-Lipid Uptake and Survival on a High-Fat Diet. Cell Metab 23:492-504
Allan, Christopher M; Procaccia, Shiri; Tran, Deanna et al. (2016) Palmoplantar Keratoderma in Slurp2-Deficient Mice. J Invest Dermatol 136:436-43
Dijk, Wieneke; Beigneux, Anne P; Larsson, Mikael et al. (2016) Angiopoietin-like 4 promotes intracellular degradation of lipoprotein lipase in adipocytes. J Lipid Res 57:1670-83
Ribas, Vicent; Drew, Brian G; Zhou, Zhenqi et al. (2016) Skeletal muscle action of estrogen receptor α is critical for the maintenance of mitochondrial function and metabolic homeostasis in females. Sci Transl Med 8:334ra54
Mysling, Simon; Kristensen, Kristian Kølby; Larsson, Mikael et al. (2016) The angiopoietin-like protein ANGPTL4 catalyzes unfolding of the hydrolase domain in lipoprotein lipase and the endothelial membrane protein GPIHBP1 counteracts this unfolding. Elife 5:
Mysling, Simon; Kristensen, Kristian Kølby; Larsson, Mikael et al. (2016) The acidic domain of the endothelial membrane protein GPIHBP1 stabilizes lipoprotein lipase activity by preventing unfolding of its catalytic domain. Elife 5:e12095
Vergnes, Laurent; Chin, Robert G; de Aguiar Vallim, Thomas et al. (2016) SREBP-2-deficient and hypomorphic mice reveal roles for SREBP-2 in embryonic development and SREBP-1c expression. J Lipid Res 57:410-21
Allan, Christopher M; Larsson, Mikael; Hu, Xuchen et al. (2016) An LPL-specific monoclonal antibody, 88B8, that abolishes the binding of LPL to GPIHBP1. J Lipid Res 57:1889-1898

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