FIG. 6.

Schematic for INH-induced lipid accumulation in genetically sensitive mouse strains. Transcriptomic analysis identified that transcriptional changes in Apoa4 and Lamp1 are associated with INH-induced microvesicular steatosis in sensitive strains. As a result, triglyceride levels are increased due to increased lipoprotein uptake and decreased lipid export. Triglycerides and sterols are then directed toward packaging in lipoproteins and lipid droplets. Transcriptomic and metabolomic analysis indicated decreased phosphatidylcholine biosynthesis due to lower levels of Chpt1, reducing the capacity for lipoprotein packing and favoring lipid droplet formation. QTL analysis identified polymorphisms in Plin2 that may inhibit lipid droplet hydrolysis resulting in lipid droplet accumulation and steatosis. Points at which INH may affect these processes by increasing (red) or decreasing (blue) key metabolites and transcripts are highlighted.