Figure 4.
Regulation of sphingolipid metabolism in NAFLD
(A) A schematic illustration of sphingolipid (SL) metabolism in human hepatocytes. Abbreviations: SPT, serine palmitoyl-CoA transferase; CerS, ceramide synthase; and DES, dihydroceramide desaturase; SMase, sphingomyelinase pathway S1P, sphingosine-1-phosphate; CDase, ceramidases; SK, sphingosine kinase; S1PPase, sphingosine phosphate phosphatases GCDase, glucosidase; GalCDase, galactosidase; C1P, ceramide 1-phosphate. The modeled reactions are labeled with ‘R#’.
(B) Averaged normalized flux differences across the SL reactions of the hepatocytes at different stages of NAFLD. Red and blue color denotes up- and downregulation of reaction fluxes within at two different stages of NAFLD. Reaction fluxes at a particular NAFLD stage was estimated by using a non-uniform random sampling method that finds solutions among the feasible flux distributions of the metabolic network. ∗p < 0.05 (two-sample t-test, adjusted for FDR).
(C) Log2 fold change (FC) of the differentially expressed (p < 0.05 adjusted for FDR) metabolic genes (MGs) of SL pathways at two different stages of NAFLD. Expression of multiple genes mapped to a particular reaction was determined by GPR rules.