Fig. 7: Fructose enhances inflammation in the presence of glucose in macrophages.

A Representative TNF and IL-1β flow cytometry plots and bar graphs of glucose (24 mM) or glucose and fructose (both 12 mM) cultured mouse macrophages treated with LPS (1 ng/mL) for 5 h in the presence of GolgiStop^TM. B Schematic of ¹³C₆-glucose (10 mM) or ¹³C₆-glucose (5 mM) and ¹³C₁-fructose (5 mM) isotope tracing. C Hexose isotopologues, m + 1 or m + 6, in mouse macrophages stimulated with LPS (1 ng/mL) for 24 h. D Glutamine uptake in the media of BMDMs cultured with 24 mM glucose or 12 mM glucose and 12 mM fructose stimulated with LPS (1 ng/mL) for 0, 12 and 24 h. E Immunoblot analysis for pS6^Ser235-236 in BMDMs stimulated with LPS overnight in the presence of glucose alone or glucose/fructose. Total S6 was used as a loading control. F Cytokine production assessed by flow cytometry and ICS for TNF, IL-1β and IL-12 of macrophages treated for 18 h with CB-839 (1 μM). G Cytokine production of TNF, IL-1β and IL-12 produced by macrophages cultured as A with or without rapamycin (50 μM). H Schematic of in vivo experiment. Mice fed a diet of 10% glucose (n = 8) or 10% glucose–fructose mixture (n = 7) for 2 weeks and stimulated with LPS (0.1 mg/kg) for 3 h (image of mouse obtained from Servier Medical Art). I Serum cytokine levels of IL-1β, IL-6 and TNF. J Schematic outlining fructose metabolism promoting inflammation. mTORC1 mammalian target of rapamycin complex 1, OXPHOS oxidative phosphorylation, TCA tricarboxylic acid. Statistical significance was assessed using an unpaired, two-tailed t test (A, I) or a two-way ANOVA with Sidak’s multiple comparison test (D, F, G). Data are representative of five (A), two (B, C), three (D–G) or seven–eight independent experiments (I) and are expressed as mean ± SEM. Source data are provided as a Source Data file.