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Review
. 2021 Feb 17:8:625331.
doi: 10.3389/fnut.2021.625331. eCollection 2021.

Adipose Tissue Macrophage Polarization in Healthy and Unhealthy Obesity

Alistaire D Ruggiero  1 , Chia-Chi Chuang Key  2 , Kylie Kavanagh  1   3
Affiliations
Review

Adipose Tissue Macrophage Polarization in Healthy and Unhealthy Obesity

Alistaire D Ruggiero et al. Front Nutr. .

Abstract

Over 650 million adults are obese (body mass index ≥ 30 kg/m2) worldwide. Obesity is commonly associated with several comorbidities, including cardiovascular disease and type II diabetes. However, compiled estimates suggest that from 5 to 40% of obese individuals do not experience metabolic or cardiovascular complications. The existence of the metabolically unhealthy obese (MUO) and the metabolically healthy obese (MHO) phenotypes suggests that underlying differences exist in both tissues and overall systemic function. Macrophage accumulation in white adipose tissue (AT) in obesity is typically associated with insulin resistance. However, as plastic cells, macrophages respond to stimuli in their microenvironments, altering their polarization between pro- and anti-inflammatory phenotypes, depending on the state of their surroundings. The dichotomous nature of MHO and MUO clinical phenotypes suggests that differences in white AT function dictate local inflammatory responses by driving changes in macrophage subtypes. As obesity requires extensive AT expansion, we posit that remodeling capacity with adipose expansion potentiates favorable macrophage profiles in MHO as compared with MUO individuals. In this review, we discuss how differences in adipogenesis, AT extracellular matrix deposition and breakdown, and AT angiogenesis perpetuate altered AT macrophage profiles in MUO compared with MHO. We discuss how non-autonomous effects of remote organ systems, including the liver, gastrointestinal tract, and cardiovascular system, interact with white adipose favorably in MHO. Preferential AT macrophage profiles in MHO stem from sustained AT function and improved overall fitness and systemic health.

Keywords: adipose; macrophage; metabolically healthy; metabolically unhealthy; obesity.

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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
Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) may be defined by differences in AT. This review focuses on macrophage phenotypes (M-Types) as a key element driving adipose health, as these immune cells have potent effects on the local AT niche and are influenced by diet and other systemic health characteristics. Differences in dietary components and aspects of adipose expansion perpetuate MHO and MUO adipose macrophage phenotypes. Increased consumption of omega 3 polyunsaturated fatty acids (n-3 PUFAs), polyphenols, and fiber results in anti-inflammatory adipose macrophage (M2) programming in MHO. These dietary components combined with improved white adipose adipogenesis and corresponding adipocyte hyperplasia increase tissue vascularization and extracellular matrix (ECM) turnover, and downstream anti-inflammatory signaling propagates anti-inflammatory M2 macrophage proliferation while abating harmful pro-inflammatory M1 macrophage recruitment into tissue. Parallel to effects of diet and adipose structure, systemic drivers, including functional liver-adipose cross talk and improved vasoreactivity, also decrease MHO AT pro-inflammatory signaling and maintain insulin sensitivity. Alternatively, increased consumption of saturated fat, cholesterols, trans fat, and fructose incites pro-inflammatory macrophage recruitment in MUO adipose. Consumption of these dietary components in conjunction with dysfunctional adipogenesis results in adipocyte hypertrophy. This combined with decreased angiogenic signals, disrupted ECM turnover, and downstream pro-inflammatory cytokine secretion stimulates pro-inflammatory M1 macrophage recruitment. Systemic dysfunction in the form of a decreased vasoreactivity and oxidative stress concurrently fosters insulin resistance while promoting pro-inflammatory M1 macrophage recruitment into MUO adipose. Once M1 macrophages enter the tissue, they secrete additional pro-inflammatory cytokines that recruit more M1 macrophages. This vicious cycle of inflammation, perpetuation of unhealthy AT, and greater multisystemic dysfunction characterize MUO individuals who are defined by increased expression of metabolic syndrome components. Created with Biorender.com.
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