Fig. 4

Acetyl Co-A related dysregulation in precancerous human and mouse lungs. (a) RNA-sequencing of biopsied lesions that either progressed or regressed, highlighted over 400 metabolites that were significant by both adjusted p value and fold change (red), which are relatively evenly distributed between up- (right) and down- (left) regulated genes. (b) Metabolic pipeline analysis of these DEGs resulted in large amounts of transcriptional dysregulation in carbohydrate (25% of significantly dysregulated pathways), amino acid (22% of significantly dysregulated pathways), and lipid/lipid-related pathways (21% of significantly dysregulated pathways – Lipid Metabolism and the lipid related pathways in Secondary Metabolites). (c) Complementary integration of paired RNA-sequencing and metabolomics in non-tumor bearing lungs of obese and non-obese mice demonstrated increased transcription (red triangles) but decreased metabolite levels (blue rectangles) of the polyamine pathway in the obese lung, suggesting utilization of Acetyl Co-A pools for acetylation of polyamines (not measured here) for exportation