title: Phosphatidylinositol 3-kinase-dependent modulation of carnitine palmitoyltransferase 1A expression regulates lipid metabolism during hematopoietic cell growth.
abstract: 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.
authors.affiliation: Abramson Family Cancer Research Institute, Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Deberardinis
authors.forename: Julian J
authors.initials: JJ
authors.lastname: Lum
authors.forename: Craig B
authors.initials: CB
authors.lastname: Thompson
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*
chemical_list: D002334:Carnitine O-Palmitoyltransferase; D019869:Phosphatidylinositol 3-Kinases