Extended Data Fig. 10: Manganese titration enables tailored treatment of dyslipidemia and ASCVD.

a, Bell-shape regulation of plasma triglyceride levels by increasing Mn²⁺ dose in drink. n = 15, 15, 8, 14, 9, and 6 mice for 0 g/L, 0.02 g/L, 0.06 g/L, 0.2 g/L, 1 g/L, and 5 g/L, respectively. Data are presented as mean ± SEM. *P values were determined by one-way ANOVA test. ^#P values were determined by the posthoc test of Tukey. Representative of 3 independent experiments is shown. b, c, Plasma samples in Fig. 7a were fractionated into VLDL, LDL and HDL by FPLC, prior to cholesterol measurement (b) and triglyceride measurement (c). Representative of 3 independent experiments is shown. d, Bell-shape regulation of plasma LDL-TG levels by increasing Mn²⁺ dose in drink. Representative of 3 independent experiments is shown. e, IB of plasma samples from Mn-supplemented hyperlipidemia mice in Fig. 7a. Representative of 3 independent experiments is shown. f, g, Mn²⁺ supplement fails to restore plasma triglycerides (f) and plasma cholesterol (g) in Surf4 LKO mice. n = 10 mice for CTL, 9 mice for Surf4 LKO. Data are presented as mean ± SEM. Statistical significance was determined by unpaired two-sided Student’s t-test. h, Plasma AST and ALT levels in mice from Fig. 7a. n = 7, 9, 8, 9, 9, and 6 mice for 0 g/L, 0.02 g/L, 0.06 g/L, 0.2 g/L, 1 g/L, 5 g/L, respectively. Data are presented as mean ± SEM. P values were determined by one-way ANOVA test. For a, d, and f-h, X-axis represent manganese doses in the drink. i, Summary of basic parameters in human samples j, k, Lack of correlation between plasma manganese concentrations and total circulating triglyceride levels (N = 297, j) or the HDL-cholesterol levels (N = 246, k) in healthy humans. Data are presented as scatter plots with the fit line and the two-sided Pearson’s correlation coefficient. Source numerical data and unprocessed blots are available in Source Data.

Source data