title: Lipid signaling in adipose tissue: Connecting inflammation & metabolism.
abstract: Obesity-associated low-grade inflammation of white adipose tissue (WAT) contributes to development of insulin resistance and other disorders. Accumulation of immune cells, especially macrophages, and macrophage polarization from M2 to M1 state, affect intrinsic WAT signaling, namely anti-inflammatory and proinflammatory cytokines, fatty acids (FA), and lipid mediators derived from both n-6 and n-3 long-chain PUFA such as (i) arachidonic acid (AA)-derived eicosanoids and endocannabinoids, and (ii) specialized pro-resolving lipid mediators including resolvins derived from both eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), lipoxins (AA metabolites), protectins and maresins (DHA metabolites). In this respect, potential differences in modulating adipocyte metabolism by various lipid mediators formed by inflammatory M1 macrophages typical of obese state, and non-inflammatory M2 macrophages typical of lean state remain to be established. Studies in mice suggest that (i) transient accumulation of M2 macrophages could be essential for the control of tissue FA levels during activation of lipolysis, (ii) currently unidentified M2 macrophage-borne signaling molecule(s) could inhibit lipolysis and re-esterification of lipolyzed FA back to triacylglycerols (TAG/FA cycle), and (iii) the egress of M2 macrophages from rebuilt WAT and removal of the negative feedback regulation could allow for a full unmasking of metabolic activities of adipocytes. Thus, M2 macrophages could support remodeling of WAT to a tissue containing metabolically flexible adipocytes endowed with a high capacity of both TAG/FA cycling and oxidative phosphorylation. This situation could be exemplified by a combined intervention using mild calorie restriction and dietary supplementation with EPA/DHA, which enhances the formation of "healthy" adipocytes. This article is part of a Special Issue entitled Oxygenated metabolism of PUFA: analysis and biological relevance."
authors.affiliation: Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment H, 1015 Lausanne, Switzerland. Electronic address: mojgan.masoodi@rd.nestle.com.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Masoodi
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Kuda
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Rossmeisl
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Flachs
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic. Electronic address: kopecky@biomed.cas.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Kopecky
mesh_terms: D017667:Adipocytes / Q000276:immunology / Q000378:metabolism; D052436:Adipose Tissue, White / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D002450:Cell Communication; D004734:Energy Metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D050356:Lipid Metabolism / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D009765:Obesity / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018836:Inflammation Mediators
keywords: Calorie restriction; Futile substrate cycle; Healthy adipocyte; Lipid mediator; Macrophage; Omega-3 fatty acids