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Adipose tissue macrophages: Unique polarization and bioenergetics in obesity.
Caslin HL, Bhanot M, Bolus WR, Hasty AH
Submitted Externally on 4/6/2020
Immunological reviews, REFERENCES
Volume : Pages
Macrophages comprise a majority of the resident immune cells in adipose tissue
(AT) and regulate both tissue homeostasis in the lean state and metabolic
dysregulation in obesity. Since the AT environment rapidly changes based upon
systemic energy status, AT macrophages (ATMs) must adapt phenotypically and
metabolically. There is a distinct dichotomy in the polarization and
bioenergetics of in vitro models, with M2 macrophages utilizing oxidative
phosphorylation (OX PHOS) and M1 macrophages utilizing glycolysis. Early studies
suggested differential polarization of ATMs, with M2-like macrophages
predominant in lean AT and M1-like macrophages in obese AT. However, recent
studies show that the phenotypic plasticity of ATMs is far more complicated,
which is also reflected in their bioenergetics. Multiple ATM populations exist
along the M2 to M1 continuum and appear to utilize both glycolysis and OX PHOS
in obesity. The significance of the dual fuel bioenergetics is unclear and may
be related to an intermediate polarization, their buffering capacity, or the
result of a mixed population of distinct polarized ATMs. Recent evidence also
suggests that ATMs of lean mice serve as a substrate buffer or reservoir to
modulate lipid, catecholamine, and iron availability. Furthermore, recent models
of weight loss and weight cycling reveal additional roles for ATMs in systemic
metabolism. Evaluating ATM phenotype and intracellular metabolism together may
more accurately illuminate the consequences of ATM accumulation in obese AT,
lending further insight into obesity-related comorbidities in humans.
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Financial support for this work was provided by the NIDDK Mouse Metabolic Phenotyping Centers (National MMPC, RRID:SCR_008997,
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