In vivo studies in which CCR2 is genetically ablated or overexpressed show that these cells mediate obesity, obesity-induced hepatic steatosis, adipose tissue inflammation, insulin insensitivity, and the associated metabolic syndrome (Figure 2) (Ito et al. 2008; Kamei et al. 2006; Kanda et al. 2006; Kim et al. 2016; Obstfeld et al. 2010). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.