Downregulation of PHGDH expression and hepatic serine level contribute to the development of fatty liver disease.

•PHGDH is an enzyme catalyzing the committed step of serine biosynthesis pathway.•Hepatic expression of PHGDH and serine concentration are decreased in steatosis animal models.•There is a significant negative correlation between the serine concentration and liver fat fraction in patients with NAFLD.•Transgenic overexpression of PHGDH in mice attenuates HFD-induced fatty liver accompanied by increased SIRT1 activity.