Intracellular long chain fatty acyl-CoAs provide the substrate for acylation reactions for membrane phospholipid biosynthesis, protein palmitoylation and cellular oxidative energy among others. Neurons have unique roles for lipids that are distinct from other cell types and are equipped with specialized machinery for regulating intracellular lipids. Although it is widely appreciated that the lipid composition of neurons is critical for human development and defects in lipid metabolism result in severe and debilitating neurological disease, there is a dearth of understanding about how neurons regulate intracellular lipid metabolism at a fundamental level. We have found that neuronal-specific acyl-CoA thioesterases are critical for neuronal development and function. We hypothesize that acyl-CoA thioesterase 7 (ACOT7) functions at an essential regulatory step for fatty acid utilization in neurons and that dysregulation of ACOT7 results in neurological dysfunction. To test this hypothesis we propose three specific aims: 1) Determine the role of ACOT7 in regulating cellular lipid metabolism. 2) Determine the neuron-specific role of ACOT7 in lipid metabolism and 3) Determine the role of ACOT7 in neurological pathophysiology.

Public Health Relevance

The rationale for these studies is that understanding the mechanisms for neuron-specific regulation of lipid metabolism will provide insight into the role of lipids in normal neurophysiology and development, and also for neurodegenerative diseases such as ALS, Parkinson's, and Alzheimer's disease which have been shown to have underlying metabolic complications. These studies will form the basis for understanding the contribution of lipids to neurological disease and enable the development of targeted therapies.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Integrative Nutrition and Metabolic Processes Study Section (INMP)
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Sutherland, Margaret L
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Johns Hopkins University
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United States
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Frey, Julie L; Kim, Soohyun P; Li, Zhu et al. (2018) ?-Catenin Directs Long-Chain Fatty Acid Catabolism in the Osteoblasts of Male Mice. Endocrinology 159:272-284
Bowman, Caitlyn E; Wolfgang, Michael J (2018) Role of the malonyl-CoA synthetase ACSF3 in mitochondrial metabolism. Adv Biol Regul :
Gonzalez-Hurtado, Elsie; Lee, Jieun; Choi, Joseph et al. (2018) Fatty acid oxidation is required for active and quiescent brown adipose tissue maintenance and thermogenic programing. Mol Metab 7:45-56
Divakaruni, Ajit S; Hsieh, Wei Yuan; Minarrieta, LucĂ­a et al. (2018) Etomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostasis. Cell Metab 28:490-503.e7
Yang, Haojun; Ralle, Martina; Wolfgang, Michael J et al. (2018) Copper-dependent amino oxidase 3 governs selection of metabolic fuels in adipocytes. PLoS Biol 16:e2006519
Xiong, Jianhua; Kawagishi, Hiroyuki; Yan, Ye et al. (2018) A Metabolic Basis for Endothelial-to-Mesenchymal Transition. Mol Cell 69:689-698.e7
Kushwaha, Priyanka; Wolfgang, Michael J; Riddle, Ryan C (2018) Fatty acid metabolism by the osteoblast. Bone 115:8-14
Jernberg, Jennifer N; Bowman, Caitlyn E; Wolfgang, Michael J et al. (2017) Developmental regulation and localization of carnitine palmitoyltransferases (CPTs) in rat brain. J Neurochem 142:407-419
Kim, Soohyun P; Li, Zhu; Zoch, Meredith L et al. (2017) Fatty acid oxidation by the osteoblast is required for normal bone acquisition in a sex- and diet-dependent manner. JCI Insight 2:
Bowman, Caitlyn E; Rodriguez, Susana; Selen Alpergin, Ebru S et al. (2017) The Mammalian Malonyl-CoA Synthetase ACSF3 Is Required for Mitochondrial Protein Malonylation and Metabolic Efficiency. Cell Chem Biol 24:673-684.e4

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