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

TLDR

Adipose tissue macrophages contribute to obesity‑associated inflammation and insulin resistance, yet their specific characteristics remain poorly defined. The study tested whether macrophages recruited to adipose tissue during a high‑fat diet possess distinct inflammatory traits compared to resident macrophages. Researchers pulse‑labeled ATMs in vivo with PKH26 and isolated the recruited macrophages from white adipose tissue of high‑fat diet mice. Recruited ATMs overexpressed migration, phagocytosis, and inflammatory genes such as IL‑6, iNOS, and CCR2, showed reduced Apoe and increased lipid‑metabolism genes, accumulated more lipid, and these changes were absent in CCR2‑knockout mice, indicating a unique inflammatory macrophage subset in obesity.

Abstract

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.