Using macrophage-specific LRP1-deficient mice (macLRP1−/−) generated on an LDLR knockout (LDLR−/−) background, which were previously used as an insulin resistance model [17], and a high fat, high cholesterol, and high sucrose (Western) diet, we reveal a proinflammatory role of macrophage LRP1 in diet-induced hepatic inflammation through modulation of the Wnt signaling pathway. The gene discussed is LRP1; the disease is Insulin resistance.