Obesogenic high-fat diet heightens aerobic glycolysis through hyperactivation of oncogenic KRAS

HFD hyperactivates oncogenic KRAS to elevate aerobic glycolysis. a Diagram of mouse treatment. TM, tamoxifen; CD (n？=？8), carbohydrate-rich diet; HFD (n？=？8), high-fat diet. b-c Western blot analysis and quantification of the expression levels of HKII in fElasCreERT and KrasG12D/+ with the indicated treatment. Three independent experiments from three different mice per group were performed. d-e Western blot analysis and quantification of the expression levels of LDHA in fElasCreERT and KrasG12D/+ with the indicated treatment. Three independent experiments from three different mice per group were performed. f-g RAS activity assay followed by Western blot analysis and quantification of the RAS-GTP levels in mice harboring fElasCreERT and KrasG12D/+ under both CD and HFD for 10 weeks. Total RAS was used as a loading control. Three independent experiments from three different mice per group were performed. h Representative IHC staining for p-ERK (upper panel) and Alcian blue staining for acidic mucins (lower panel) as indicated. Magnifications: 200x. (n？=？6 mice per group). i Statistical analysis of p-ERK (n？=？6) as represented in Fig. 1h (upper panel). j Statistical analysis of the Alcian Blue staining (n？=？6) as represented in Fig. 1h (lower panel). Data are mean？±？SD. p values are determined by the Student’s t-test. *p？<？0.05; **p？<？0.01; ***p？<？0.001; ****p？<？0.000