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Berberine-induced activation of AMPK increases hepatic FGF21 expression via NUR77

Feiye Zhou, Mengyao Bai, Yuqing Zhang, Qin Zhu, Linlin Zhang, Qi Zhang, Shushu Wang, Kecheng Zhu, Yun Liu, Xiao Wang, Libin Zhou
Biochemical and Biophysical Research Communications 2018 January 8, 495 (2): 1936-1941
Fibroblast growth factor 21 (FGF21), a hormone-like protein mainly derived from liver, exhibits multiple beneficial effect on energy metabolism. Similar to FGF21, berberine exerts anti-hyperglycemic and anti-dyslipidemic properties. Previous studies revealed that the beneficial metabolic effect of berberine was attributed to the activation of AMP-activated protein kinase (AMPK). Here we investigated the effect of berberine on FGF21 expression in primary mouse hepatocytes. As expected, berberine induced hepatic FGF21 expression in a dose-dependent and time-dependent manner, along with the increased expression of NUR77, a proved transcription factor of FGF21. Berberine stimulated the phosphorylations of AMPK and acetyl-CoA carboxylase in primary mouse hepatocytes. Adenovirus-mediated overexpression of constitutively active AMPK triggered hepatic FGF21 and NUR77 expressions. The inhibition of AMPK by compound C abolished berberine-stimulated FGF21 and NUR77 expressions. These results suggest that berberine-induced activation of AMPK may contribute to hepatic FGF21 expression via NUR77.


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