The Ron receptor tyrosine kinase, macrophage heterogeneity and obesity associated disease. (P5070)

Abstract

Abstract Macrophages play a central role in the progression of obesity associated disease. Macrophages are generally classified into two distinct programs, termed M1 and M2 macrophages, polar ends of a spectrum of potential macrophage activation states. The ability to tip the balance of macrophage activation away from inflammatory M1 cells and toward a reparative M2 phenotype could be beneficial in the treatment of chronic inflammation associated with obesity. The Ron receptor is expressed on tissue resident macrophages and plays a critical role in suppressing inflammation while promoting hallmarks of M2 macrophage activation. Here we show that Ron plays a protective role in the progression of atherosclerosis and hepatic steatosis in obese animals, associated with decreased inflammatory cytokine expression and decreased lipid deposition in these tissues. In lean animals, Ron is highly expressed on resident macrophages in adipose tissue. Upon weight gain, the expression of Ron is decreased and there is shift in the relative percentages of M1/M2 cells in Ron deficient mice, favoring an inflammatory environment. The percentage of Ron+ cells was also reduced in the liver and atherosclerotic plaques, while pro-inflammatory cytokine expression in isolated macrophages was enhanced in the absence of Ron. We predict that Ron is a potential marker for reparative macrophages and that the gene expression profile of macrophages from obese animals will correlate with Ron expression in these cells.