Acute inflammation upregulates FAHFAs in adipose tissue and in co-cultured adipocytes.

Autor:	Ertunc ME; Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, USA. Electronic address: meric@post.harvard.edu., Konduri S; The Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA., Ma Z; The Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA., Pinto AFM; Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, USA., Donaldson CJ; Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, USA., Momper J; The Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA., Siegel D; The Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA. Electronic address: drsiegel@ucsd.edu., Saghatelian A; Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, USA. Electronic address: asaghatelian@salk.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Nov 05, pp. 107972. Date of Electronic Publication: 2024 Nov 05.
DOI:	10.1016/j.jbc.2024.107972
Abstrakt:	Since the discovery of fatty acid hydroxy fatty acids (FAHFAs), significant progress has been made in understanding their regulation, biochemistry, and physiological activities. Here, we contribute to this understanding by revealing that inflammation induces the production of fatty acid hydroxy stearic acids (FAHSAs) and fatty acid hydroxyoctadecadienoic acids (FAHODEs) in white adipose tissue depots and in adipocytes co-cultured with macrophages. In LPS-induced co-culture systems, we confirm that adipose triglyceride lipase (ATGL) is required for inflammation-induced FAHFA generation and demonstrate that inflammation is necessary for producing hydroxy fatty acids. Chemically synthesized FAHODEs show anti-inflammatory activities in vivo, but only at supraphysiological concentrations. While endogenous FAHFAs are unlikely to be anti-inflammatory due to their low concentrations, conversion of pro-inflammatory hydroxy fatty acids into FAHFAs may modulate inflammation. We test this concept by showing the pro-inflammatory lipids-hydroxyeicosatetraenoic acids (HETEs) and leukotriene B4 (LTB4)-are converted into FAHFAs in cell culture, and that two LTB4-derived FAHFAs have are modestly anti- not pro-inflammatory. Further research is needed to establish whether these increased FAFHA levels have a role in inflammation or are simply markers of inflammation, but the discovery of significant increases in FAHFA upon acute inflammation advances our knowledge of FAHFAs. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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