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. 2022 Oct 19;8(42):eadc9022. doi: 10.1126/sciadv.adc9022

Fig. 2. Altered oxysterol synthesis (OHC) and sulfation (OHCS) result in sterol misbalance in Atp7b−/− liver.

Fig. 2.

(A) Cartoon illustrating effects of modified sterols on LXR activity. (B) Relative abundances of the transcripts for enzymes involved in OHC synthesis (Cyp450) and (C) for sulfotransferases involved in OHCS production (n = 4 male mice per group). (D) qPCR analysis of mRNA at 12 and 20 weeks shows a genotype (KO) and time-dependent up-regulation of Sult1e1 transcript (n = 5 to 10 male mice per group). (E) Liver oxysterols (4-OHC, 7-OHC, 24-OHC, 25-OHC, and Chol) and 4-OHCS and 7-OHCS were significantly reduced in KO mice. (F) Oxysterol sulfates (24-OHCS, 25-OHCS, 27-OHCS, and DHEAS) were significantly elevated in the KO liver. Values represent means ± SD. *P < 0.05, **P < 0.01, ***P < 0.001, ****P<0.0001, n = 6 male mice per group. Blue color denotes Het, and red color denotes KO, respectively. Chol, cholesterol; 4-OHC, 4-hydroxycholesterol; 7-OHC, 7-hydroxycholesterol; 24-OHC, 24-hydroxycholesterol; 25-OHC, 25-hydroxycholesterol; 4-OHCS, 4-hydroxychole-sterol-3-sulfate; 7-OHCS, 7-hydroxycholesterol-3-sulfate; 24-OHCS, 24-hydroxy-cholesterol-3-sulfate; 25-OHCS, 25-hydroxychole-sterol-3-sulfate; 27-OHCS, 27-hydroxycholesterol-3-sulfate; DHEAS, dehydroepiandrosterone sulfate; ns, nonsignificant.