Fig. 8.

Effect of lowering GRK2 levels in myeloid cells in the modulation of the adipose-liver crosstalk. In obesity, chemokines stimulate the infiltration of macrophages into the WAT promoting a pro-inflammatory phenotype in adipose tissue macrophages, which contribute to the development of a persistent, low-grade inflammation. Pro-inflammatory mediators in WAT induce IR and further enhance monocyte recruitment, perpetuating a self-fed cycle of inflammation and altering adipokine expression pattern. The dysfunctional WAT and its infiltrating pro-inflammatory macrophages fuel hepatic IR, lipid accumulation and the activation of Kupffer cells within the liver. Decreased levels of GRK2 in myeloid cells reduce the pro-inflammatory response of macrophages in the face of a HFD, fostering a less inflamed adipose tissue, a preserved adipokine secretion pattern, and a decreased expression of inflammatory cytokines. This reduces activation of Kupffer cells and subsequent recruitment of macrophages in the liver, protects from IR and steatosis and preserves overall metabolic homeostasis. Arrows represent the effect of lowering GRK2 on the different processes. Stars represent M2 (green) or M1 (brown) macrophages