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.

中文翻译：

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脂肪组织巨噬细胞：肥胖中独特的极化和生物能学。


巨噬细胞包含脂肪组织（AT）中的大部分常驻免疫细胞，并调节瘦状态下的组织稳态和肥胖状态下的代谢失调。由于 AT 环境会根据全身能量状态而迅速变化，因此 AT 巨噬细胞 (ATM) 必须在表型和代谢上进行适应。体外模型的极化和生物能学存在明显的二分性，M2 巨噬细胞利用氧化磷酸化 (OX PHOS)，M1 巨噬细胞利用糖酵解。早期研究表明 ATM 存在不同的极化，M2 样巨噬细胞在瘦 AT 中占主导地位，而 M1 样巨噬细胞在肥胖 AT 中占主导地位。然而，最近的研究表明，ATM 的表型可塑性要复杂得多，这也反映在其生物能学中。多个 ATM 群体沿着 M2 到 M1 连续体存在，并且似乎在肥胖中同时利用糖酵解和 OX PHOS。双燃料生物能学的重要性尚不清楚，可能与中间极化、其缓冲能力或不同极化 ATM 混合群体的结果有关。最近的证据还表明，瘦小鼠的 ATM 可作为底物缓冲液或储库来调节脂质、儿茶酚胺和铁的利用率。此外，最近的减肥和体重循环模型揭示了 ATM 在全身代谢中的额外作用。一起评估 ATM 表型和细胞内代谢可能会更准确地阐明肥胖 AT 中 ATM 积累的后果，从而进一步了解人类与肥胖相关的合并症。