title: Macrophage-secreted factors induce adipocyte inflammation and insulin resistance.
abstract: Macrophage infiltration into adipose tissue increases with obesity, a condition associated with low-grade inflammation and insulin resistance. We investigated the direct effects of macrophage-secreted factors on adipocyte inflammation and insulin resistance. 3T3-L1 adipocytes incubated with media conditioned by RAW264.7 macrophages (RAW-CM) showed dramatically increased transcription of several inflammation-related genes, greater nuclear factor kappa B (NF-kappaB) activity, and enhanced binding of U937 monocytes. All of these effects were prevented by co-incubation with pyrrolidinedithiocarbamate, an NF-kappaB inhibitor. Adipocytes incubated with RAW-CM also released more non-esterified fatty acids and this increased lipolysis was not suppressed by insulin. In addition, RAW-CM treatment decreased insulin-stimulated glucose uptake in adipocytes. Taken together, these results indicate that macrophage-secreted factors induce inflammatory responses and reduce insulin responsiveness in adipocytes. These effects of macrophage-secreted factors on adipocytes may contribute significantly to the systemic inflammation and insulin resistance associated with obesity.
authors.affiliation: Research Service, Carl T. Hayden Veterans Affairs Medical Center, Phoenix, AZ 85012-1892, USA. Paska.Permana@med.va.gov
authors.forename: Paska A
authors.initials: PA
authors.lastname: Permana
authors.forename: Christopher
authors.initials: C
authors.lastname: Menge
authors.forename: Peter D
authors.initials: PD
authors.lastname: Reaven
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D015233:Models, Statistical; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D020298:U937 Cells
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D007328:Insulin; D015850:Interleukin-6; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D018799:Intercellular Adhesion Molecule-1; C020972:pyrrolidine dithiocarbamic acid; D012313:RNA; D005947:Glucose