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Increased Inflammatory Properties of Adipose Tissue Macrophages Recruited During Diet-Induced Obesity

¹ Life Sciences Institute, University of Michigan, Ann Arbor, Michigan
² Department of Pediatrics and Communicable Diseases, University of Michigan Medical Center, Ann Arbor, Michigan
³ Departments of Internal Medicine and Physiology, University of Michigan Medical School, Ann Arbor, Michigan

Address correspondence and reprint requests to Alan R. Saltiel PhD, Life Sciences Institute, 210 Washtenaw Ave., Ann Arbor, MI 48109. E-mail: saltiel{at}lsi.umich.edu

Abbreviations: apo, apolioprotein; ATM, adipose tissue macrophage; CCR2, C-C chemokine receptor 2; DAPI, 4,6-diamidino-2-phenylindole; FACS, fluorescence-activated cell sorter; GRK3, G-protein–coupled receptor kinase 3; IL, interleukin; iNOS, inducible nitric oxide synthase; MCP-1, monocyte chemoattractant protein 1; SVF, stromal vascular fraction; TNF-, tumor necrosis factor-

Although recent studies show that adipose tissue macrophages (ATMs) participate in the inflammatory changes in obesity and contribute to insulin resistance, the properties of these cells are not well understood. We hypothesized that ATMs recruited to adipose tissue during a high-fat diet have unique inflammatory properties compared with resident tissue ATMs. Using a dye (PKH26) to pulse label ATMs in vivo, we purified macrophages recruited to white adipose tissue during a high-fat diet. Comparison of gene expression in recruited and resident ATMs using real-time RT-PCR and cDNA microarrays showed that recruited ATMs overexpress genes important in macrophage migration and phagocytosis, including interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and C-C chemokine receptor 2 (CCR2). Many of these genes were not induced in ATMs from high-fat diet–fed CCR2 knockout mice, supporting the importance of CCR2 in regulating recruitment of inflammatory ATMs during obesity. Additionally, expression of Apoe was decreased, whereas genes important in lipid metabolism, such as Pparg, Adfp, Srepf1, and Apob48r, were increased in the recruited macrophages. In agreement with this, ATMs from obese mice had increased lipid content compared with those from lean mice. These studies demonstrate that recruited ATMs in obese animals represent a subclass of macrophages with unique properties.

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