Phosphatidylinositol 3-kinase-dependent modulation of carnitine palmitoyltransferase 1A expression regulates lipid metabolism during hematopoietic cell growth

Ralph J. DeBerardinis, Julian J. Lum, Craig B. Thompson

Research output: Contribution to journalArticle

148 Citations (Scopus)

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 β-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 β-oxidation enzyme carnitine palmitoyltransferase 1A (CPT1A). Cells expressing a short hairpin RNA against CPT1A fail to induce β-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 β-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 β-oxidation during anabolic growth.

Original languageEnglish (US)
Pages (from-to)37372-37380
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number49
DOIs
StatePublished - Dec 8 2006

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Phosphatidylinositol 3-Kinase
Carnitine O-Palmitoyltransferase
Cell growth
Lipid Metabolism
Intercellular Signaling Peptides and Proteins
Modulation
Oxidation
Growth
Lipids
Nutrients
Food
Interleukin-3
Small Interfering RNA
Cell proliferation
Macromolecules
Cell Proliferation
Glucose
Chemical activation
Cells
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Phosphatidylinositol 3-kinase-dependent modulation of carnitine palmitoyltransferase 1A expression regulates lipid metabolism during hematopoietic cell growth. / DeBerardinis, Ralph J.; Lum, Julian J.; Thompson, Craig B.

In: Journal of Biological Chemistry, Vol. 281, No. 49, 08.12.2006, p. 37372-37380.

Research output: Contribution to journalArticle

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