How ketogenic diet reshapes cancer metabolism
Multi-omics analysis of mouse livers shows that protein lysine β-hydroxybutyrylation (Kbhb) is strongly affected by the ketogenic diet. How cellular processes are regulated by Kbhb is not clear.
Combining bioinformatics with experimental validation, a role of Kbhb sites in modulating mammalian target of rapamycin signalling and cancer cell metabolism is identified.
Using various techniques, mechanistically, the researchers found that KD consumption or β-hydroxybutyrate supplementation in hepatocellular carcinoma cells increases ALDOB Lys108bhb and inhibits the enzymatic activity of ALDOB.
A Kbhb-mimicking mutation (p.Lys108Gln) attenuates ALDOB activity and its binding to substrate fructose-1,6-bisphosphate, inhibits mammalian target of rapamycin signalling and glycolysis, and markedly suppresses cancer cell proliferation.
