Figure 2.

The regulation of hepatic FGF21. The expression of FGF21 is tightly connected with circadian rhythm, diet intervention, exercise, and cold exposure. The circadian rhythm of FGF21 is controlled by several clock proteins. PPARα and RORα positively activate the expression of FGF21 while REV-ERBα and E4BP4 repress its transcription; Exercise stimulates FGF21 expression via the increased plasma glucagon to insulin ratio, and this process positively correlated with the elevated lipolysis and decreased glucose levels; Diet regimen has magnificent impacts on FGF21 levels, both nutrient proportions and food timing are implicated in the complex regulation system of FGF21; Increased FGF21 is also observed under cold exposure which may be cooperated with the thermogenic response of BAT to maintain body temperature.