Macro partitioning
In obesity and type 2 diabetes, adipose tissue macrophages undergo 'metabolic activation' characterized by high glycolysis and lipid internalization, which drives insulin resistance and chronic inflammation without exhibiting the classical M1 activation markers.
In obesity, fat tissue immune cells change their metabolism to fuel chronic inflammation and insulin resistance. This is not a standard immune response but a specific 'metabolic' adaptation. Understanding this helps explain why weight loss and metabolic health improvements are key to resolving this specific type of inflammation.
Even though levels of pro-inflammatory cytokines produced by macrophages in obesity are higher compared to non-obese individuals, contributing to the onset of obesity related meta-inflammation, their activation status does not coincide with a classically activated status of macrophages... This macrophage subset is defined as metabolically activated and specific markers for this type of macrophages are suggested to be macrophage scavenger receptor 1 (Msr1), ATP-binding cassette A1 (ABCA1), and the adipose differentiation-related protein (Perilipin-2, PLIN2), in addition to CD11c and CD36.
Why this rating
This is a review paper citing multiple primary studies (e.g., Xu et al., Dahik et al.) establishing the phenotype.
Source
Meta-Inflammation and Metabolic Reprogramming of Macrophages in Diabetes and Obesity: The Importance of Metabolites
Sara Russo et al. · Frontiers in Immunology · 2021
DOI 10.3389/fimmu.2021.746151
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- Classically activated (M1) macrophages reprogram their metabolism to favor aerobic glycolysis and lactate production over oxidative phosphorylation, leading to TCA cycle interruptions and accumulation of metabolites like citrate and succinate.Strong
- Accumulation of succinate and itaconate in classically activated macrophages stabilizes HIF-1alpha, which promotes further glycolysis and inflammation, creating a feedback loop.Good
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