Macro partitioning
In obesity, the accumulation of classically activated (M1) macrophages in adipose tissue drives insulin resistance through the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and the activation of stress kinases (JNK, IKK, p38 MAPK) that inhibit insulin receptor signaling.
Obesity triggers an immune response in fat tissue where immune cells (M1 macrophages) become inflamed and block insulin's ability to work. This happens because excess fat releases signals that activate these immune cells. Managing body weight and reducing fat mass can help reverse this inflammatory state and improve insulin sensitivity.
During obesity, AT M1 macrophage numbers increase and correlate with AT inflammation and insulin resistance. Upon activation, pro-inflammatory M1 macrophages induce aerobic glycolysis... These cytokines are secreted by both adipocytes and ATMs due to increased levels of pro-inflammatory factors... These factors include FFA, triglycerides, resistin, leptin, retinol-binding protein 4 (RBP4), IL-6, TNF-α, and IL-1β... These alterations lead to decreased tyrosine phosphorylation of insulin receptor substrate (IRS-1 and -2)... and consequently insulin resistance.
Why this rating
Based on a comprehensive review of multiple in vivo knockout models (TLR4, NLRP3, JNK, mTOR) and human clinical correlations.
Source
The Macrophage Switch in Obesity Development
Ângela Castoldi et al. · Frontiers in Immunology · 2016
DOI 10.3389/fimmu.2015.00637
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