AMPK acts as a master regulator of metabolism in cells, regulating glucose uptake, fatty acid breakdown, and mitochondrial biogenesis. Studies in mice have shown that inhibiting AMPK decreases appetite and weight, while activating AMPK increases appetite and weight. Additional studies show that dietary restriction activates AMPK in myeloid leukemia, AMPK is required for maintaining leukemia initiating cells in myeloid leukemias, and inhibiting AMPK can make leukemia initiating cells vulnerable to metabolic stress caused by dietary changes.

1. Journal Club
11.01.16

2. AMPK - Master Regulator
• AMPK acts as a metabolic master switch regulating several intracellular systems
including the cellular uptake of glucose, the β-oxidation of fatty acids and the
biogenesis of glucose transporter 4 (GLUT4) and mitochondria.
• A JBC (2009) paper on mice at Johns Hopkins has shown that when the activity of
brain AMPK was pharmacologically inhibited, the mice ate less and lost weight.
When AMPK activity was pharmacologically raised the mice ate more and gained
weight.

4. Dietary Restriction Activates AMPK in
MLL-AF9-Induced AML

5. AMPK Is Required for the Maintenance of LICs
in Myeloid Leukemias
Conditional deletion of AMPK from
established AMLs by treating mice carrying MLLAF9-
transduced Ubc-Cre-ERT2; AMPKa fl/fl AML
cells with tamoxifen led to significant extension of
survival and reduced frequency of L-GMPs in
the bone marrow, but not in the spleens
LIC

6. AMPK Suppresses ROS and DNA
Damage in AML

7. AMPK Promotes Glucose Uptake and Metabolism
in AML

8. AMPK Regulates Glucose Metabolism

9. DR Suppresses AMPK-Deficient AML
Compound C (AMPK inh.)

10. AMPK inhibition can make LICs residing in the hypoxic
bone marrow environment vulnerable to physiological metabolic
stress caused by changes in diet