Retinol binding protein 4 primes the NLRP3 inflammasome by signaling through Toll-like receptors 2 and 4
Inflammation
Mice, Knockout
2. Zero hunger
0301 basic medicine
Inflammasomes
Adipose Tissue, White
Macrophages
Interleukin-1beta
Models, Biological
Toll-Like Receptor 2
Mice, Inbred C57BL
Mice
03 medical and health sciences
Glucose
3T3-L1 Cells
NLR Family, Pyrin Domain-Containing 3 Protein
Adipocytes
Animals
Humans
Insulin Resistance
Glycolysis
Retinol-Binding Proteins, Plasma
Signal Transduction
DOI:
10.1073/pnas.2013877117
Publication Date:
2020-11-20T02:02:51Z
AUTHORS (8)
ABSTRACT
Significance
There is a growing need for insulin-sensitizing therapies to treat type 2 diabetes (T2D). In obese T2D humans, NLRP3 inflammasome activation contributes to insulin resistance. Serum levels of retinol binding protein 4 (RBP4) are elevated in obese, insulin-resistant humans and RBP4 SNPs that increase adipose RBP4 expression confer greater T2D risk. RBP4 levels correlate with many metabolic syndrome-related components, including cardiovascular disease. RBP4 elevation induces insulin resistance in mice by increasing proinflammatory cytokine secretion from macrophages. Reducing RBP4 in mice with dietary obesity decreases adipose inflammation and improves insulin sensitivity. Here we show RBP4 primes the NLRP3 inflammasome which plays a critical role in RBP4-induced insulin resistance. Thus, the NLRP3-RBP4 axis may provide therapeutic strategies for T2D and its comorbidities.
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CITATIONS (67)
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