Fig. 9: Expression of JMJD3, TFEB, and autophagy genes is reduced in NAFLD patients.

Liver samples from normal, simple steatosis and NASH-fibrosis patients were analyzed. a The mRNA levels of the indicated genes measured by q-RTPCR (n = 15 individuals). b Levels of the indicated proteins in liver samples detected by IB (left, n = 4 normal, n = 5 patients, 3 to 4 pooled samples/lane) and quantified (right). c LC3, JMJD3, and ATG7 were detected in liver sections by IHC. LC3 puncta are indicated by yellow arrows (scale bar = 10 μm for LC3, 50 μm for JMJD3 and ATG7). Source data are provided as a Source Data file. a, b Values are presented as mean ± SD. Statistical significance was measured using the a, b one-way ANOVA with the Bonferroni post-test. *P < 0.05, **P < 0.01, and NS statistically not significant. d Model: in response to fasting, JMJD3 is phosphorylated at Thr-1044 by FGF21 signaling-activated PKA in mouse hepatocytes, which promotes its nuclear localization and interaction with the nuclear receptor PPARα to epigenetically induce transcription of genes involved in autophagy and lipid degradation, including Atg7, Ulk1, Atgl, Tfeb, and Pgc-1α, and as a positive feed-forward loop, JMJD3 and FGF21 expression. Induced hepatic FGF21 sustains the activation of the FGF21-JMJD3-autophagy axis in an autocrine manner when fasting continues.