| First Author | Deberardinis RJ | Year | 2006 |
| Journal | J Biol Chem | Volume | 281 |
| Issue | 49 | Pages | 37372-80 |
| PubMed ID | 17030509 | Mgi Jnum | J:292522 |
| Mgi Id | MGI:6450291 | Doi | 10.1074/jbc.M608372200 |
| Citation | Deberardinis RJ, et al. (2006) Phosphatidylinositol 3-kinase-dependent modulation of carnitine palmitoyltransferase 1A expression regulates lipid metabolism during hematopoietic cell growth. J Biol Chem 281(49):37372-80 |
| abstractText | An abundant supply of extracellular nutrients is believed to be sufficient to suppress catabolism of cellular macromolecules. Here we show that, despite abundant extracellular nutrients, interleukin-3-deprived hematopoietic cells begin to catabolize intracellular lipids. Constitutive Akt activation blunts the increased beta-oxidation that accompanies growth factor withdrawal, and in growth factor-replete cells, phosphatidylinositol 3-kinase (PI3K) signaling is required to suppress lipid catabolism. Surprisingly, PI3K and Akt exert these effects by suppressing expression of the beta-oxidation enzyme carnitine palmitoyltransferase 1A (CPT1A). Cells expressing a short hairpin RNA against CPT1A fail to induce beta-oxidation in response to growth factor withdrawal and are unable to survive glucose deprivation. When CPT1A is constitutively expressed, growth factor stimulation fails to repress beta-oxidation. As a result, both net lipid synthesis and cell proliferation are diminished. Together, these results demonstrate that modulation of CPT1A expression by PI3K-dependent signaling is the major mechanism by which cells suppress beta-oxidation during anabolic growth. |
