Macrophage polarization in metabolic disorders: functions and regulation

Abstract

Purpose of review: To discuss recent findings on the role and regulation of macrophage polarization in obesity and atherosclerosis.

Recent findings: Macrophages infiltrate the vascular wall during atherosclerosis and adipose tissue during obesity. At least two distinct subpopulations with different functions, the classically (M1) and the alternatively (M2) activated macrophages, have been found in these tissues. Reciprocal skewing of macrophage polarization between the M1 and M2 states is a process modulated by diet, humoral and transcription factors, such as the nuclear receptor peroxisome proliferator-activated receptor gamma.

Summary: Recent literature highlights the importance not only of the number of infiltrated macrophages, but also their activation in the maintenance of the inflammation state. Identifying mechanisms and molecules able to modify the balance between M1 and M2 represents a promising field of research.

Figure 1

Circulating monocytes can infiltrate the vascular wall during atherosclerosis and adipose tissue during obesity and can differentiate in different macrophage sub-populations, exemplified by the extreme pro-inflammatory M1 and anti-inflammatory M2 macrophage subtypes

Figure 2

PPARγ activation promotes alternative macrophage differentiation. IL-4 induces PPARγ expression and activity by generating natural PPARγ ligands via the 12/15-lipoxygenase (12/15 LOX) pathway PPARγ activation by its ligands promotes monocyte differentiation toward M2 macrophages in mice and humans.