Fig. 5

A Genome-scale metabolic modelling to simulate the impact of fatty acid treatment and metabolic enzyme inhibition on the metabolic network of hepatocytes. Heatmap of z-transformed reaction flux differences between the oleic acid vs control medium and ACLY, CPT, ACS2 KO vs wild type control in oleic acid-treated cells. p < 0.05 in any condition. B Average number of cells with high ɣH2AX after oleic acid or oleic acid plus drug treatments (% compared to control cells). Error bars are ± SEM. All groups n = 8. *P < 0.05, ***P < 0.0001 in t-test of oleic vs oleic plus inhibitor groups. C Select genes from the RNA-seq showing oleic acid-induced alteration to biological processes, oxidative stress response (GPX1, GPX4), lipotoxicity (ATF4), lipid droplet formation (PLIN2), acetyl-coA metabolism (PDK4, ACSS2, ACLY), β-oxidation (CPT1), the TCA cycle (CS), histone acetylation and chromatin condensation (KAT6B, HMGA1), folate metabolism (MTHFR), retinol dehydrogenase (RDH11) and aldehyde dehydrogenase (ALDH5A1). Garcinol treatment had little or no impact on any of these genes and processes. Error bars are ± SEM. All groups n = 4. *P < 0.05, **P < 0.001, ***P < 0.0001 in t-test of control vs oleic group, ^P < 0.05 in t-test of garcinol vs oleic group