title: Increased macrophage migration into adipose tissue in obese mice.
abstract: Macrophage-mediated inflammation is a key component of insulin resistance; however, the initial events of monocyte migration to become tissue macrophages remain poorly understood. We report a new method to quantitate in vivo macrophage tracking (i.e., blood monocytes from donor mice) labeled ex vivo with fluorescent PKH26 dye and injected into recipient mice. Labeled monocytes appear as adipose, liver, and splenic macrophages, peaking in 1-2 days. When CCR2 KO monocytes are injected into wild-type (WT) recipients, or WT monocytes given to MCP-1 KO recipients, adipose tissue macrophage (ATM) accumulation is reduced by ~40%, whereas hepatic macrophage content is decreased by ~80%. Using WT donor cells, ATM accumulation is several-fold greater in obese recipient mice compared with lean mice, regardless of the source of donor monocytes. After their appearance in adipose tissue, ATMs progressively polarize from the M2- to the M1-like state in obesity. In summary, the CCR2/MCP-1 system is a contributory factor to monocyte migration into adipose tissue and is the dominant signal controlling the appearance of recruited macrophages in the liver. Monocytes from obese mice are not programmed to become inflammatory ATMs but rather the increased proinflammatory ATM accumulation in obesity is in response to tissue signals.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: Da Young
authors.initials: DY
authors.lastname: Oh
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Morinaga
authors.forename: Saswata
authors.initials: S
authors.lastname: Talukdar
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Bae
authors.forename: Jerrold M
authors.initials: JM
authors.lastname: Olefsky
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D039521:CD11c Antigen / Q000032:analysis; D002465:Cell Movement; D016764:Cell Polarity; D018932:Chemokine CCL2 / Q000502:physiology; D008099:Liver / Q000473:pathology; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009000:Monocytes / Q000502:physiology; D009765:Obesity / Q000473:pathology*; D054390:Receptors, CCR2 / Q000502:physiology
chemical_list: D039521:CD11c Antigen; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2