INS and obesity due to melanocortin 4 receptor deficiency: FGF21 increases energy expenditure and decreases body weight and blood glucose, insulin, and hepatic triglyceride concentrations in rodent models of obesity, in part by acting directly on the nervous system to induce sympathetic outflow to BAT and WAT, promoting in turn thermogenesis and “browning” in these tissues [71,72,73,74] (Figure 2).