Fig. 2: Estrogens regulate hepatic PNPLA3 mRNA expression.

a, Hepatic PNPLA3 expression in patients in the transcriptomic cohort (n = 125 individuals with obesity) stratified by sex and carriage of the PNPLA3 p.I148M variant. In the box and whisker plots, the line in the middle of the box represents the medians, tops and bottoms of the boxes the 25th and 75th quartiles, respectively, and the whiskers the minimum to maximum value. The impact of the variant was estimated using generalized linear regression models adjusted for age and batch. b, IPA of differentially regulated genes in women carrying the PNPLA3 p.I148M variant. Terms are reported with a P < 0.05 after a Benjamini–Hochberg (B-H) correction. PKA, Protein kinase A. c, Predicted activation state of upstream cytokines, transcription factors and enzymes in women carrying the p.I148M variant. d, The mRNA levels of Pnpla3 from RNA-seq analysis performed in the livers of male and female mice at low and high levels of E₂. Data are presented as mean ± s.e.m. (n = 4 independent male and female high E₂ mice; n = 3 independent female low E₂ mice). One-way ANOVA was followed by Bonferroni’s post hoc test.

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