Remarkably, overproduced interleukin-6 (IL-6) from adipose tissue macrophages (ATM) in obesity accounts for elevated basal lipolysis, which leads to production of excessive acetyl-CoA in the liver eliciting hepatic glucose production (HGP) and insulin insensitivity in mice (2, 14). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.