Development and Application of FASA, a Model for Quantifying Fatty Acid Metabolism Using Stable Isotope Labeling.

Autor:	Argus JP; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, 615 Charles E. Young Drive East, Los Angeles, CA 90095, USA., Wilks MQ; Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, 149, 13(th) Street, Charlestown, MA 02129, USA., Zhou QD; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, 615 Charles E. Young Drive East, Los Angeles, CA 90095, USA; Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China., Hsieh WY; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, 615 Charles E. Young Drive East, Los Angeles, CA 90095, USA., Khialeeva E; Molecular Biology Institute, University of California, Los Angeles, 611 Charles E. Young Drive East, Los Angeles, CA 90095, USA., Hoi XP; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, 615 Charles E. Young Drive East, Los Angeles, CA 90095, USA., Bui V; Division of Rheumatology, David Geffen School of Medicine, University of California, Los Angeles, 1000 Veteran Avenue, Los Angeles, CA 90095, USA., Xu S; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, 615 Charles E. Young Drive East, Los Angeles, CA 90095, USA., Yu AK; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, 615 Charles E. Young Drive East, Los Angeles, CA 90095, USA., Wang ES; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, 615 Charles E. Young Drive East, Los Angeles, CA 90095, USA., Herschman HR; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, 615 Charles E. Young Drive East, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, 611 Charles E. Young Drive East, Los Angeles, CA 90095, USA., Williams KJ; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, 615 Charles E. Young Drive East, Los Angeles, CA 90095, USA., Bensinger SJ; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, 615 Charles E. Young Drive East, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, 615 Charles E. Young Drive East, Los Angeles, CA 90095, USA. Electronic address: sbensinger@mednet.ucla.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2018 Dec 04; Vol. 25 (10), pp. 2919-2934.e8.
DOI:	10.1016/j.celrep.2018.11.041
Abstrakt:	It is well understood that fatty acids can be synthesized, imported, and modified to meet requisite demands in cells. However, following the movement of fatty acids through the multiplicity of these metabolic steps has remained difficult. To better address this problem, we developed Fatty Acid Source Analysis (FASA), a model that defines the contribution of synthesis, import, and elongation pathways to fatty acid homeostasis in saturated, monounsaturated, and polyunsaturated fatty acid pools. Application of FASA demonstrated that elongation can be a major contributor to cellular fatty acid content and showed that distinct pro-inflammatory stimuli (e.g., Toll-like receptors 2, 3, or 4) specifically reprogram homeostasis of fatty acids by differential utilization of synthetic and elongation pathways in macrophages. In sum, this modeling approach significantly advances our ability to interrogate cellular fatty acid metabolism and provides insight into how cells dynamically reshape their lipidomes in response to metabolic or inflammatory signals. (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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