A decade of progress in adipose tissue macrophage biology

Abstract

Summary One decade has passed since seminal publications described macrophage infiltration into adipose tissue (AT) as a key contributor to inflammation and obesity-related insulin resistance. Currently, a PubMed search for ‘adipose tissue inflammation’ reveals over 3500 entries since these original reports. We now know that resident macrophages in lean AT are alternatively activated, M2-like, and play a role in AT homeostasis. In contrast, the macrophages in obese AT are dramatically increased in number and are predominantly classically activated, M1-like, and promote inflammation and insulin resistance. Mediators of AT macrophage (ATM) phenotype include adipokines and fatty acids secreted from adipocytes as well as cytokines secreted from other immune cells in AT. There are several mechanisms that could explain the large increase in ATMs in obesity. These include recruitment-dependent mechanisms such as adipocyte death, chemokine release, and lipolysis of fatty acids. Newer evidence also points to recruitment-independent mechanisms such as impaired apoptosis, increased proliferation, and decreased egress. Although less is known about the homeostatic function of M2-like resident ATMs, recent evidence suggests roles in AT expansion, thermoregulation, antigen presentation, and iron homeostasis. The field of immunometabolism has come a long way in the past decade, and many exciting new discoveries are bound to be made in the coming years that will expand our understanding of how AT stands at the junction of immune and metabolic co-regulation.

ABCG1 regulates mouse adipose tissue macrophage cholesterol levels and ratio of M1 to M2 cells in obesity and caloric restriction

“…Obesity is accompanied by increased infl ammation as evidenced systemically by elevations in circulating infl ammatory cytokines and in adipose tissue due to the accumulation of adipose tissue macrophages (ATMs) ( 6,7 ). ATMs are broadly characterized as classically activated (M1), producing proinfl ammatory proteins, and alternatively activated (M2) macrophages based on their responses to specifi c T helper (Th) 1 and Th2 cytokines (8)(9)(10).…”

Impact of Pioglitazone on Macrophage Dynamics in Adipose Tissues of Cecal Ligation and Puncture-Treated Mice

“…8,9,13,14) Hence, given our previous and progressing findings, we considered that cross-talk between adipocytes and macrophages in visceral adipose tissue might play an important role in the development of several diseases. Adipose tissue macrophages are divided into three different phenotypes: classically activated M1 macrophages, alternatively activated M2 macrophages, and deactivated macrophages.…”

“…Inflammatory M1 macro- phages produce many pro-inflammatory cytokines which promote inflammation leading to insulin resistance, and promote T helper 1 (Th1) response and possess strong microbicidal and tumoricidal activities, while M2 macrophages are involved in the promotion of T helper 2 (Th2) response, tissue remodeling, immune tolerance, and anti-inflammatory response. 8,15,27,28) Watanabe et al 29) has more recently reported that sepsis induces an incomplete polarization to the M2 macrophages in peritoneal exudate cells in CLP mice. In the present study, CLP markedly enhanced the levels of Arg1 and IL-10 mRNA expression serving as M2 markers in septic mice.…”

“…Adipose tissue includes pre-adipocytes, vascular cells, and hemocytes. Adipose regulatory T cells 6) and macrophages [7][8][9] have crucial roles in adipose tissue inflammation. Pioglitazone, a peroxisome proliferator-activated receptor (PPAR) γ activator, improved the survival rate in association with increased serum adiponectin levels in cecal ligation and puncture (CLP)-treated mice.…”

High-Fat Diet–Induced Obesity Enhances Allograft Rejection

“…At the cellular level, adipocytes produce inflammatory cytokines that enhance the prevalence of local proinflammatory M1 macrophages at the expense of anti-inflammatory and tissue-repairing M2 macrophages 7 . The change in the local cytokine milieu also impacts the local adaptive immune system, by recruiting CD4 + Th1 and CD8 + cytotoxic T cells while depleting Th2 and regulatory T (Tregs) cells involved in tissue homeostasis 8 .…”