Inflammatory Mediators and Insulin Resistance in Obesity: Role of Nuclear Receptor Signaling in Macrophages
Figure 2
Tissue-resident macrophages are sources and targets of inflammatory mediators in obesity. (a) Liver-resident macrophages (Kupffer cells) are major sources of inflammatory cytokines in obesity and IR. Free fatty acids (FFAs) and oxidized low density lipoproteins (oxLDL) released from VAT promote M1 phenotype polarization through activation of TLRs. The switch to the M2 phenotype is promoted by PPARδ signaling. Inflammatory mediators (IL-6, TNFα, and IL-1β) originating from M1 Kupffer cells or adipose tissue macrophages (ATMs) induce hepatocyte apoptosis, IR, and lipid accumulation. (b) Osteoclastogenesis is induced by ATM-derived inflammatory cytokines in obesity and IR. Activation of PPARs blocks osteoclastogenesis and impedes bone loss, while LXR promotes osteoclast resorptive activity.
