Fig. 5: Depletion of LRRC58 stabilizes CDO1 and regulates hepatic cholesterol and fatty acid metabolism.

a–c, Proteomics analysis (a) and LRRC58 (b) and CDO1 (c) abundance in the liver of WT and LRRC58^KD mice. Tissue specificity of LRRC58 knockdown is shown in Extended Data Fig. 9b,c. LRRC58^KD, n = 8 male mice; scr, n = 7 male mice. Number of mice was limited by the throughput of a tandem mass tag (TMT) plex for proteomics. d, Hepatic cholesterol levels in WT and LRRC58^KD mice. LRRC58^KD, n = 12 male mice; scr, n = 11 male mice. e, Hepatic cysteine levels in WT and LRRC58^KD mice. LRRC58^KD, n = 12 male mice; scr, n = 11 male mice. f, ¹³C₂¹⁵N₁-taurine abundance in liver of scr and LRRC58^KD mice following intravenous administration of ¹³C₆¹⁵N₂-labelled l-cystine for 30 min. LRRC58^KD, n = 9 male mice; scr, n = 9 male mice. g, Hepatic total bile acid (BA) levels in WT and LRRC58^KD mice. LRRC58^KD, n = 12 male mice; scr, n = 11 male mice. h, Biliary cholesterol levels in WT and LRRC58^KD mice. LRRC58^KD, n = 12 male mice; scr, n = 9 male mice (gallbladder extraction failed for 2 mice). i, Hepatic triacylglyceride (TG) levels in WT and LRRC58^KD mice. LRRC58^KD, n = 11 male mice; scr, n = 11 male mice. j, Hepatic abundance of fatty acyl-carnitines in WT and LRRC58^KD mice. LRRC58^KD, n = 12 male mice; scr, n = 11 male mice. k, Hepatic cholesterol levels measured in DO mice livers with highest (top 8%) LRRC58 abundance compared with lowest (bottom 8%) LRRC58 abundance. Two-tailed Student’s t-test for pairwise comparisons (a–k). Data are mean ± s.e.m.

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