Research progress into adipose tissue macrophages and insulin resistance

Abstract

In recent years, there has been an increasing incidence of metabolic syndrome, type 2 diabetes, and cardiovascular events related to insulin resistance. As one of the target organs for insulin, adipose tissue is essential for maintaining in vivo immune homeostasis and metabolic regulation. Currently, the specific adipose tissue mechanisms involved in insulin resistance remain incompletely understood. There is increasing evidence that the process of insulin resistance is mostly accompanied by a dramatic increase in the number and phenotypic changes of adipose tissue macrophages (ATMs). In this review, we discuss the origins and functions of ATMs, some regulatory factors of ATM phenotypes, and the mechanisms through which ATMs mediate insulin resistance. We explore how ATM phenotypes contribute to insulin resistance in adipose tissue. We expect that modulation of ATM phenotypes will provide a novel strategy for the treatment of diseases associated with insulin resistance.

Fig. 1

“Crown-like structures (CLS)” in adipose tissue. Macrophages surround the necrotic adipocytes and form “CLS”. During this process, recruited macrophages are predominantly of the M1 phenotype, and secrete a variety of pro-inflammatory factors. Therefore, “CLS” is considered as one of the hallmarks of adipose tissue inflammation.

Fig. 2

Plasticity of macrophage phenotypes. Macrophages exhibit different phenotypes and perform their respective functions in response to different stimuli. M1 macrophages mainly show pro-inflammatory effects, whereas M2 macrophages (including M2a, 2b, 2c, and 2d) mainly show anti-inflammatory effects and promote tissue repair. IFN-γ = interferon-γ; LPS = lipopolysaccharide; TNF = tumor necrosis factor; IL = interleukin; TGF-β = transforming growth factor-β; ICs = immune complexes; TLR = Toll-like receptor; IL-1R = interleukin-1 receptor; A2R = A2 adenosine receptor.

Fig. 3

Insulin signaling pathway. The binding of insulin to the receptor causes phosphorylation of insulin receptor substrate(IRS), after which the catalytic activity of PI3K is activated, leading to the activation of Akt, which mediates glucose transport through glucose transporter 4 (GLUT4). Meanwhile, activated Akt continues to activate downstream signaling pathways to regulate glucose homeostasis. It is worth mentioning that in adipose tissue, the inhibition of lipolysis and gluconeogenesis by insulin may be associated with phosphodiesterase 3B (PDE3B), protein phosphatase 1 (PP1), and protein phosphatase 2A (PP2A). IRS = insulin receptor substrate; PI3K = phosphatidylinositol 3 kinase; PIP2 = phosphatidylinositol 4,5-bisphosphate; PIP3 = phosphatidylinositol 3,4,5-trisphosphate; PDK1 = phosphoinositide-dependent protein kinase 1; PDE3B = phosphodiesterase 3B; PP1 = protein phosphatase 1; PP2A = protein phosphatase 2A; GLUT4 = glucose transporter 4.