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Review
. 2023 Feb 16:14:1148188.
doi: 10.3389/fimmu.2023.1148188. eCollection 2023.

Capturing the multifaceted function of adipose tissue macrophages

Affiliations
Review

Capturing the multifaceted function of adipose tissue macrophages

Alyssa J Matz et al. Front Immunol. .

Abstract

Adipose tissue macrophages (ATMs) bolster obesity-induced metabolic dysfunction and represent a targetable population to lessen obesity-associated health risks. However, ATMs also facilitate adipose tissue function through multiple actions, including adipocyte clearance, lipid scavenging and metabolism, extracellular remodeling, and supporting angiogenesis and adipogenesis. Thus, high-resolution methods are needed to capture macrophages' dynamic and multifaceted functions in adipose tissue. Herein, we review current knowledge on regulatory networks critical to macrophage plasticity and their multifaceted response in the complex adipose tissue microenvironment.

Keywords: adipose tissue; immune response; macrophage; obesity; single-cell RNA sequencing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
ATMs experience a complex microenvironment with opposing and compounding signals that results in a spectrum of activity. (A) Key stimuli, receptors, and signaling cascades known to control macrophage actions and implicated in ATM biology. (From Left to Right) M1-polarizing cytokines include TNF-α and IFN-γ. M1-polarizing chemokines are also present in AT and include CCL2, CCL4, and CXCL8. DAMPS= Danger-associated molecular patterns including exogenous (lipopolysaccharide) and endogenous signaling (e.g. apoptotic cells) are recognized through TLR4 to elicit pro-inflammatory signaling (JAK-STAT/NK-κB/MAPK) towards the production of type-1 cytokines (TNF-α, IL-1β, IFN-γ). miR-155 promotes M1-polarization through inhibition of signaling cascades towards PPARγ. FFA= Free Fatty Acids signaling through TLR4 elicits pro-inflammatory activation; CD36 transports FFAs, upregulating fatty acid oxidation and OXPHOS= Oxidative Phosphorylation. CD36 also recognizes DAMPs to activate pro-inflammatory activation. M2-polarizing cytokines (IL-4, IL-13, IL-10, IL-17A, IL-25) activate PPARγ to produce type-2 cytokines (IL-10, TGF-β). miR-223 promotes M2-polarization through the repression of pro-inflammatory signal cascade components. OXPHOS is required for M2 actions. Adipocyte-derived exosomes transport neutral lipids (including TAG=Triacylglycerols) into macrophages, which induce lysosomal biogenesis for lipid metabolism. Trem2 and Tim4 also elicit lysosomal biogenesis, but the ligands and downstream signaling cascades are unclear. (B) Macrophages are plastic, responding to diverse stimuli to provide appropriate action. Due to the plasticity of macrophages, their multifaceted capacity, and the complex microenvironment in AT, a single ATM can perform various actions. The ATM population is best represented as a spectrum of macrophage functions.

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