title: Resolvin D1 and resolvin D2 govern local inflammatory tone in obese fat.
abstract: The unprecedented increase in the prevalence of obesity and obesity-related disorders is causally linked to a chronic state of low-grade inflammation in adipose tissue. Timely resolution of inflammation and return of this tissue to homeostasis are key to reducing obesity-induced metabolic dysfunctions. In this study, with inflamed adipose, we investigated the biosynthesis, conversion, and actions of Resolvins D1 (RvD1, 7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) and D2 (RvD2, 7S,16R,17S-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid), potent anti-inflammatory and proresolving lipid mediators (LMs), and their ability to regulate monocyte interactions with adipocytes. Lipid mediator-metabololipidomics identified RvD1 and RvD2 from endogenous sources in human and mouse adipose tissues. We also identified proresolving receptors (i.e., ALX/FPR2, ChemR23, and GPR32) in these tissues. Compared with lean tissue, obese adipose showed a deficit of these endogenous anti-inflammatory signals. With inflamed obese adipose tissue, RvD1 and RvD2 each rescued impaired expression and secretion of adiponectin in a time- and concentration-dependent manner as well as decreasing proinflammatory adipokine production including leptin, TNF-α, IL-6, and IL-1β. RvD1 and RvD2 each reduced MCP-1 and leukotriene B₄-stimulated monocyte adhesion to adipocytes and their transadipose migration. Adipose tissue rapidly converted both resolvins (Rvs) to novel oxo-Rvs. RvD2 was enzymatically converted to 7-oxo-RvD2 as its major metabolic route that retained adipose-directed RvD2 actions. These results indicate, in adipose, D-series Rvs (RvD1 and RvD2) are potent proresolving mediators that counteract both local adipokine production and monocyte accumulation in obesity-induced adipose inflammation.
authors: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors: Joan
authors: J
authors: Clària
authors: Jesmond
authors: J
authors: Dalli
authors: Stephanie
authors: S
authors: Yacoubian
authors: Fei
authors: F
authors: Gao
authors: Charles N
authors: CN
authors: Serhan
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004281:Docosahexaenoic Acids / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D050151:Subcutaneous Fat / Q000473:pathology*
chemical_list: D018836:Inflammation Mediators; C518399:resolvin D1; C545423:resolvin D2; D004281:Docosahexaenoic Acids