Dietary saturated fatty acids prime the NLRP3 inflammasome via TLR4 in dendritic cells—implications for diet-induced insulin resistance

摘要: Scope Inflammasome-mediated inflammation is a critical regulator of obesity-induced insulin resistance (IR). We hypothesized that saturated fatty acids (SFA) directly prime the NLRP3 inflammasome via TLR4 concurrent with IR. focused on dendritic cells (DCs) (CD11c(+) CD11b(+) F4/80(-) ), which are recruited into obese adipose tissue following high-fat diet (HFD) challenge and key cell in biology. Methods results C57BL/6 mice were fed HFD for 16 weeks (45% kcal palm oil), glucose homeostasis was monitored by tolerance tests. Stromal vascular fraction (SVF) isolated from analyzed CD11c(+) F480(-) DC. Following coculture bone marrow derived DC (BMDC) insulin-stimulated (3) H-glucose transport adipocytes, IL-1β secretion caspase-1 activation monitored. BMDCs primed LPS (100 ng/mL), linoleic acid (LA; 200 μM), or palmitic (PA; μM) used to monitor activation. demonstrated significant infiltration DCs after HFD. HFD-derived reduce adipocyte sensitivity upon co-incident enhanced activation/IL-1β secretion. skewed toward pro-inflammatory phenotype increased secretion, IL-1R1, TLR4, expression. Complementary vitro experiments demonstrate propagating SFA-mediated Conclusion SFA represent metabolic triggers priming inflammasome, promoting inflammation/IR, suggesting direct effects TLR4.