Extended Data Fig. 10: Fructose enhances de novo lipogenesis but not circulating glucose and aspartate.

(a) Relative total pool (sum of all labeled and unlabeled isotopologues) of serum glucose after gavaging C57BL/6 mice with 0.5 g/kg of [U-¹³C] fructose (n = 4) at t = 0. (b) Relative total pool (sum of all labeled and unlabeled isotopologues) of serum aspartate after gavaging C57BL/6 mice with 0.5 g/kg of [U-¹³C] fructose (n = 4) at t = 0. (c) Total ¹³C-labelling in serum glucose after introducing 0.5 g/kg [U-¹³C] fructose via oral gavage to C57 BL/6 mice bearing TC-1 tumours (n = 4 in each condition). (d) Western blot analysis against acetyl-CoA carboxylase (ACC) from C57 BL/6 mouse livers after 6 weeks of a control diet supplemented with normal water (Control), 10% glucose water (Glc water), 10% fructose water (Frc water), or 20 % HFCS (HFCS). (e) Western blot analysis of ACC from C57 BL/6 mouse livers after 5 days of a control diet supplemented with normal water (Control), 10% fructose water (10% Frc water), or 10% fructose water + 50 mg/kg/day i.p. injection of PF-06835919 (10% Frc Water + PF-06835919). (f) Quantification of gel in (e), normalizing ACC band to the beta tubulin loading control. Relative deuterium enrichment for (g) hepatic palmitate, (h) hepatic stearate, and (i) hepatic oleate from C57 BL/6 mice given 50% D₂O for 12 h. Before the administration of D₂O, mice were pretreated with normal drinking water (n = 3-4), 10% fructose water (n = 5), or 10% fructose water + 50 mg/kg/day i.p. injection PF-06835919 (n = 5) for 7 days. The mice were maintained under these same conditions while administering 50% D₂O water. All experiments for this figure were performed once. P value determined by two-way ANOVA with Šídák’s multiple comparisons test (c) or ordinary one-way ANOVA with Tukey’s multiple comparisons test (e, g-i). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, and n.s. is not significant. All data shown as mean ± standard deviation.

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