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CPT1alpha over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells

Item Type:Article
Title:CPT1alpha over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells
Creators Name:Jambor de Sousa, U.L. and Koss, M.D. and Fillies, M. and Gahl, A. and Scheeder, M.R.L. and Cardoso, M.C. and Leonhardt, H. and Geary, N. and Langhans, W. and Leonhardt, M.
Abstract:To test the cellular response to an increased fatty acid oxidation, we generated a vector for an inducible expression of the rate-limiting enzyme carnitine palmitoyl-transferase 1{alpha} (CPT1{alpha}). Human embryonic 293T kidney cells were transiently transfected and expression of the CPT1{alpha} transgene in the tet-on vector was activated with doxycycline. Fatty acid oxidation was measured by determining the conversion of supplemented, synthetic cis-10-heptadecenoic acid (C17:1n-7) to C15:ln-7. CPT1{alpha} over-expression increased mitochondrial long-chain fatty acid oxidation about 6-fold. Addition of palmitic acid (PA) decreased viability of CPT1α over-expressing cells in a concentration-dependent manner. Both, PA and CPT1{alpha} over-expression increased cell death. Interestingly, PA reduced total cell number only in cells over-expressing CPT1{alpha}, suggesting an effect on cell proliferation that requires PA translocation across the mitochondrial inner membrane. This inducible expression system should be well suited to study the roles of CPT1 and fatty acid oxidation in lipotoxicity and metabolism in vivo.
Keywords:CPT1 Alpha, Lipotoxicity, Long-chain fatty acids, Mitochondria
Source:Biochemical and Biophysical Research Communications
ISSN:0006-291X
Publisher:Academic Press (U.S.A.)
Volume:338
Number:2
Page Range:757-761
Date:12 October 2005
Official Publication:https://doi.org/10.1016/j.bbrc.2005.10.016
PubMed:View item in PubMed

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