Properties and functions of adipose tissue macrophages in obesity

Abstract

The expansion of adipose tissue (AT) in obesity is accompanied by the accumulation of immune cells that contribute to a state of low-grade, chronic inflammation and dysregulated metabolism. Adipose tissue macrophages (ATMs) represent the most abundant class of leukocytes in AT and are involved in the regulation of several regulatory physiological processes, such as tissue remodeling and insulin sensitivity. With progressive obesity, ATMs are key mediators of meta-inflammation, insulin resistance and impairment of adipocyte function. While macrophage recruitment from blood monocytes is a critical component of the generation of AT inflammation, new studies have revealed a role for ATM proliferation in the early stages of obesity and in sustaining AT inflammation. In addition, studies have revealed a more complex range of macrophage activation states than the previous M1/M2 model, and the existence of different macrophage profiles between human and animal models. This review will summarize the current understanding of the regulatory mechanisms of ATM function in relation to obesity, type 2 diabetes, depot of origin, and to other leukocytes such as AT dendritic cells, with hopes of emphasizing the regulatory nodes that can potentially be targeted to prevent and treat obesity-related metabolic disorders.

Monounsaturated Fatty Acids in a High‐Fat Diet and Niacin Protect from White Fat Dysfunction in the Metabolic Syndrome

“…Olive‐oil‐based HFDs was found to have the efficacy of preventing more than half the number of macrophages (F4/80 positive cells) found increased in WAT of mice on the milk‐cream‐based HFD. As lower is the cellularity and thereby the recruitment of macrophages, the lower is the inflammatory state and the better is the adipocyte function and physiological response to insulin in WAT . This is crucial to avoid the advance of adipose tissue macrophage‐driven inflammation under sustained conditions of metabolic pressure induced by dietary fat overload.…”

“…Worthy of noting is the fact that the number of adipose‐resident and M1 macrophages was recently noticed to increase in mice with selective ablation of SIRT1 in adipocytes, indicating that NAD + biosynthesis and signaling could share an underlying link with phenotypic changes of adipose macrophages. The diversity and heterogeneity of macrophages in WAT and other tissues are highly dependent on local microenvironments and currently envisioned as plastic cell populations with a continuum of functional phenotypes, the extremes of which are called classic or M1 and alternative or M2 macrophages, with obesity‐ and metabolic‐syndrome‐associated cues introducing new unwelcome subset variants such as metabolic activated and oxidized macrophages toward the M1 end of the activation spectrum . Classically activated macrophages M1 are producers of pro‐inflammatory mediators, while alternatively activated M2 cells are concerned with the modulation of pro‐inflammatory response by the production of anti‐inflammatory, immunosuppressive, and clearing inflammatory molecules for resolution.…”

Adipokines and the control of mast cell functions: from obesity to inflammation?

“…While leptin generally drives inflammatory responses, adiponectin can operate to suppress inflammation. Thus, increased adiposity can lead to a condition of chronic inflammation, affecting immune cells including macrophages and T cells . These responses are caused in large part by changes in expression of leptin and adiponectin …”

Knowns and unknowns of tissue‐resident memory T cells

“…A number of recent papers have considered features of the tissue-resident populations at different sites, including lung, adipose tissue and brain, noting that not only TRM cells, but also Tregs, macrophages and dendritic cells show tissue-specific, resident, phenotypes. [3][4][5][6][7][8][9] There is much still to be learnt about the anatomical localization and connectivity of tissue-resident immune populations. MacLeod and colleagues have speculated that clustering of TRM cells with APC and B cells may be a step on the way to formation of the ectopic lymphoid follicles that often mark out inflammatory tissues.…”

“…Interestingly, the bulk of this core signature is shared between TRM from different tissues, with only a small subset defining the difference between, for example, spleen versus lung. A number of recent papers have considered features of the tissue‐resident populations at different sites, including lung, adipose tissue and brain, noting that not only TRM cells, but also Tregs, macrophages and dendritic cells show tissue‐specific, resident, phenotypes …”