Experimental study demonstrates that TLR4 deficiency protects against lipid-induced insulin resistance in mice, indicating innate immunity regulates nutrient-driven metabolic dysfunction.
Key Points
To determine whether Toll-like receptor 4 (TLR4) mediates fatty acid-induced inflammatory signaling and obesity-associated insulin resistance.
Assessed TLR4-dependent inflammatory signaling in response to nutritional fatty acids using cultured adipocytes and macrophages.
Administered systemic lipid infusions to wild-type and TLR4-deficient mice to evaluate muscle insulin signaling and systemic glucose metabolism.
Maintained female wild-type and TLR4-deficient C57BL/6 mice on a high-fat diet to measure body weight, insulin sensitivity, and tissue inflammatory gene expression.
Nutritional fatty acids stimulated TLR4 inflammatory signaling in adipocytes and macrophages, an effect that was blunted in cells lacking TLR4.
Mice lacking TLR4 were protected from lipid infusion-mediated suppression of muscle insulin signaling and reductions in systemic glucose clearance.
TLR4-deficient female mice fed a high-fat diet developed greater obesity but remained partially protected against insulin resistance, accompanied by reduced inflammatory gene expression in fat and liver tissue.