Macrophage LRP1 Promotes Diet-Induced Hepatic Inflammation and Metabolic Dysfunction by Modulating Wnt Signaling

Figure 6

Proposed role of macrophage LRP1 depicted in diet-induced inflammatory conditions. Under proinflammatory conditions, macrophage LRP1 sequesters sFRP-5 to modulate the Wnt signaling pathway and its downstream effectors. LRP1 mediates activation of p38 MAPK which in turn inactivates GSK3. This causes impaired glucose tolerance, dysregulation of glycogen metabolism, and insulin resistance. Altogether, body weight gain with impaired metabolic function is observed in mice. APC: adenomatous polyposis coli; Dvl: dishevelled; Fz: frizzled; sFRP-5: secreted frizzled-related protein 5; GSK3: glycogen synthase kinase 3; LRP1: lipoprotein receptor-related protein 1; LRP5/6: lipoprotein receptor-related protein 5/6; p38 MAPK: p38 mitogen-activated protein kinase; TCF/LEF: T cell factor/lymphoid enhancing factor; Wnt: wingless-related integration site.

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