After knocking out or over-expressing the Sik2 gene in mice, the concentration of intracellular calcium ions was increased by the activation of the sympathetic nerve, which activated the cAMP-PKA pathway and increased phosphorylation of Sik2 significantly, leading to the increase of UCP-1 expression and enhancing the brown adipose metabolism to reduce the incidence of obesity in mice [79]. Here, SIK2 is linked to obesity due to melanocortin 4 receptor deficiency.