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Titos, EAuthorRius, BAuthorMoran-Salvador, ECorresponding AuthorArroyo, VAuthorClaria, JCorresponding Author

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Resolvin D1 and Its Precursor Docosahexaenoic Acid Promote Resolution of Adipose Tissue Inflammation by Eliciting Macrophage Polarization toward an M2-Like Phenotype

Publicated to:Journal Of Immunology. 187 (10): 5408-5418 - 2011-11-15 187(10), DOI: 10.4049/jimmunol.1100225

Authors: Titos, Esther; Rius, Bibiana; Gonzalez-Periz, Ana; Lopez-Vicario, Cristina; Moran-Salvador, Eva; Martinez-Clemente, Marcos; Arroyo, Vicente; Claria, Joan

Affiliations

Biomed Res Networking Ctr Liver & Digest Dis, Barcelona 08036, Spain - Author
Department of Biochemistry and Molecular Genetics, Hospital Clinic, Center Esther Koplowitz, August Pi i Sunyer Biomedical Research Institute, 08036 Barcelona, Spain. esther.titos@ciberehd.org - Author
Hosp Clin Barcelona, Ctr Esther Koplowitz, Dept Biochem & Mol Genet, August Pi & Sunyer Biomed Res Inst, E-08036 Barcelona, Spain - Author
Hosp Clin Barcelona, Liver Unit, Dept Biochem & Mol Genet, August Pi & Sunyer Biomed Res Inst, E-08036 Barcelona, Spain - Author
Univ Barcelona, Dept Physiol Sci 1, E-08036 Barcelona, Spain - Author
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Abstract

We recently demonstrated that ?-3-polyunsaturated fatty acids ameliorate obesity-induced adipose tissue inflammation and insulin resistance. In this study, we report novel mechanisms underlying ?-3-polyunsaturated fatty acid actions on adipose tissue, adipocytes, and stromal vascular cells (SVC). Inflamed adipose tissue from high-fat diet-induced obese mice showed increased F4/80 and CD11b double-positive macrophage staining and elevated IL-6 and MCP-1 levels. Docosahexaenoic acid (DHA; 4 ?g/g) did not change the total number of macrophages but significantly reduced the percentage of high CD11b/high F4/80-expressing cells in parallel with the emergence of low-expressing CD11b/F4/80 macrophages in the adipose tissue. This effect was associated with downregulation of proinflammatory adipokines in parallel with increased expression of IL-10, CD206, arginase 1, resistin-like molecule ?, and chitinase-3 like protein, indicating a phenotypic switch in macrophage polarization toward an M2-like phenotype. This shift was confined to the SVC fraction, in which secretion of Th1 cytokines (IL-6, MCP-1, and TNF-?) was blocked by DHA. Notably, resolvin D1, an anti-inflammatory and proresolving mediator biosynthesized from DHA, markedly attenuated IFN-?/LPS-induced Th1 cytokines while upregulating arginase 1 expression in a concentration-dependent manner. Resolvin D1 also stimulated nonphlogistic phagocytosis in adipose SVC macrophages by increasing both the number of macrophages containing ingested particles and the number of phagocytosed particles and by reducing macrophage reactive oxygen species production. No changes in adipocyte area and the phosphorylation of hormone-sensitive lipase, a rate-limiting enzyme regulating adipocyte lipolysis, were observed. These findings illustrate novel mechanisms through which resolvin D1 and its precursor DHA confer anti-inflammatory and proresolving actions in inflamed adipose tissue.

Keywords

AccumulationAdipose tissueAnimalsCell polarityCognitive impairmentDementiaDietDisease models, animalDocosahexaenoic acidsDysfunctionHepatic steatosisImmunophenotypingInflammation mediatorsInsulin-resistanceMacrophage activationMacrophagesMaleMiceMice, inbred c57blMice, obeseObesityPrevalenceRandom allocationRecognitionResolvin d1Signal transduction

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Immunology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2011, it was in position 20/139, thus managing to position itself as a Q1 (Primer Cuartil), in the category Immunology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 30.01, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-28, the following number of citations:

  • WoS: 335
  • Scopus: 364
  • Europe PMC: 245

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-28:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 230.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 230 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 3.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: BETHESDA.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Titos Rodriguez, Esther) and Last Author (Claria Enrich, Joan).

the authors responsible for correspondence tasks have been Moran Salvador, Eva and Claria Enrich, Joan.