Published online before print June 7, 2001, doi: 10.1161/hh1201.092998
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2001 American Heart Association, Inc.
Cellular Biology |
Acute Regulation of Fatty Acid Oxidation and AMP-Activated Protein Kinase in Human Umbilical Vein Endothelial Cells
From the Departments of Medicine and Physiology (Z.D., N.R.), Boston University School of Medicine, Boston, Mass, and Diabetes and Metabolism Unit (Z.D., N.R., K.T., Y.I.), Section of Endocrinology, Boston University Medical Center, Boston, Mass.
Correspondence to Neil Ruderman, Diabetes and Metabolism Unit, Boston University Medical Center, 650 Albany St No. 820, Boston, MA 02118. E-mail nruderman{at}med-med1.bu.edu
Abstract
Abstract—It is generally accepted that endothelial cells generate most of their ATP by anaerobic glycolysis and that very little ATP is derived from the oxidation of fatty acids or glucose. Previously, we have reported that, in cultured human umbilical vein endothelial cells (HUVECs), activation of AMP-activated protein kinase (AMPK) by the cell-permeable activator 5-aminoimidazole-4-carboximide riboside (AICAR) is associated with an increase in the oxidation of 3H-palmitate. In the present study, experiments carried out with cultured HUVECs revealed the following: (1) AICAR-induced increases in palmitate oxidation during a 2-hour incubation are associated with a decrease in the concentration of malonyl coenzyme A (CoA) (an inhibitor of carnitine palmitoyl transferase 1), which temporally parallels the increase in AMPK activity and a decrease in the activity of acetyl CoA carboxylase (ACC). (2) AICAR does not stimulate either palmitate oxidation when carnitine is omitted from the medium or oxidation of the medium-chain fatty acid octanoate. (3) When intracellular lipid pools are prelabeled with 3H-palmitate, the measured rate of palmitate oxidation is 3-fold higher, and in the presence of AICAR, it accounts for nearly 40% of calculated ATP generation. (4) Incubation of HUVECs in a glucose-free medium for 2 hours causes the same changes in AMPK, ACC, malonyl CoA, and palmitate oxidation as does AICAR. (5) Under all conditions studied, the contribution of glucose oxidation to ATP production is minimal. The results indicate that the AMPK–ACC–malonyl CoA–carnitine palmitoyl transferase 1 mechanism plays a key role in the physiological regulation of fatty acid oxidation in HUVECs. They also indicate that HUVECs oxidize fatty acids from both intracellular and extracellular sources, and that when this is taken into account, fatty acids can be a major substrate for ATP generation. Finally, they suggest that AMPK is likely to be a major factor in modulating the response of the endothelium to stresses that alter its energy state.
Key Words: glucose transport • AICAR • malonyl CoA • acetyl CoA carboxylase • fuel metabolism
This article has been cited by other articles:
 |
|
 |
|
  L. H. Young AMP-Activated Protein Kinase Conducts the Ischemic Stress Response Orchestra Circulation, February 12, 2008; 117(6): 832 - 840. [Full Text] [PDF]
|
|
|
|
 |
|
 Z. T. Bloomgarden Insulin Resistance Concepts Diabetes Care, May 1, 2007; 30(5): 1320 - 1326. [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Davidson and M. R. Duchen Endothelial Mitochondria: Contributing to Vascular Function and Disease Circ. Res., April 27, 2007; 100(8): 1128 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Towler and D. G. Hardie AMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling Circ. Res., February 16, 2007; 100(3): 328 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Lopez-Lopez, M. O. Dietrich, F. Metzger, H. Loetscher, and I. Torres-Aleman Disturbed Cross Talk between Insulin-Like Growth Factor I and AMP-Activated Protein Kinase as a Possible Cause of Vascular Dysfunction in the Amyloid Precursor Protein/Presenilin 2 Mouse Model of Alzheimer's Disease J. Neurosci., January 24, 2007; 27(4): 824 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Saks, R. Favier, R. Guzun, U. Schlattner, and T. Wallimann Molecular system bioenergetics: regulation of substrate supply in response to heart energy demands J. Physiol., December 15, 2006; 577(3): 769 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Sun, T.-S. Lee, M. Zhu, C. Gu, Y. Wang, Y. Zhu, and J. Y-J. Shyy Statins Activate AMP-Activated Protein Kinase In Vitro and In Vivo Circulation, December 12, 2006; 114(24): 2655 - 2662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Lee-Young, M. J. Palmer, K. C. Linden, K. LePlastrier, B. J. Canny, M. Hargreaves, G. D. Wadley, B. E. Kemp, and G. K. McConell Carbohydrate ingestion does not alter skeletal muscle AMPK signaling during exercise in humans Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E566 - E573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. G. K. de Aguiar, L. R. Bahia, N. Villela, C. Laflor, F. Sicuro, N. Wiernsperger, D. Bottino, and E. Bouskela Metformin Improves Endothelial Vascular Reactivity in First-Degree Relatives of Type 2 Diabetic Patients With Metabolic Syndrome and Normal Glucose Tolerance Diabetes Care, May 1, 2006; 29(5): 1083 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Quintero, S. L. Colombo, A. Godfrey, and S. Moncada Mitochondria as signaling organelles in the vascular endothelium PNAS, April 4, 2006; 103(14): 5379 - 5384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. da Silva, R. Jarzyna, A. Specht, and E. Kaczmarek Extracellular Nucleotides and Adenosine Independently Activate AMP-Activated Protein Kinase in Endothelial Cells: Involvement of P2 Receptors and Adenosine Transporters Circ. Res., March 17, 2006; 98(5): e39 - e47. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Ning, T. J. Chu, C. J. Li, A. M. K. Choi, and D. G. Peters Genome-wide analysis of the endothelial transcriptome under short-term chronic hypoxia Physiol Genomics, June 17, 2004; 18(1): 70 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Goldstein and R. Scalia Adiponectin: A Novel Adipokine Linking Adipocytes and Vascular Function J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2563 - 2568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. B. Ruderman, A. K. Saha, and E. W. Kraegen Minireview: Malonyl CoA, AMP-Activated Protein Kinase, and Adiposity Endocrinology, December 1, 2003; 144(12): 5166 - 5171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-H. Zou, X.-Y. Hou, C.-M. Shi, S. Kirkpatick, F. Liu, M. H. Goldman, and R. A. Cohen Activation of 5'-AMP-activated Kinase Is Mediated through c-Src and Phosphoinositide 3-Kinase Activity during Hypoxia-Reoxygenation of Bovine Aortic Endothelial Cells: ROLE OF PEROXYNITRITE J. Biol. Chem., September 5, 2003; 278(36): 34003 - 34010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. A. Morrow, F. Foufelle, J. M. C. Connell, J. R. Petrie, G. W. Gould, and I. P. Salt Direct Activation of AMP-activated Protein Kinase Stimulates Nitric-oxide Synthesis in Human Aortic Endothelial Cells J. Biol. Chem., August 22, 2003; 278(34): 31629 - 31639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Nagata, M. Mogi, and K. Walsh AMP-activated Protein Kinase (AMPK) Signaling in Endothelial Cells Is Essential for Angiogenesis in Response to Hypoxic Stress J. Biol. Chem., August 15, 2003; 278(33): 31000 - 31006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. I. Itani, A. K. Saha, T. G. Kurowski, H. R. Coffin, K. Tornheim, and N. B. Ruderman Glucose Autoregulates Its Uptake in Skeletal Muscle: Involvement of AMP-Activated Protein Kinase Diabetes, July 1, 2003; 52(7): 1635 - 1640. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. E. Mann, D. L. Yudilevich, and L. Sobrevia Regulation of Amino Acid and Glucose Transporters in Endothelial and Smooth Muscle Cells Physiol Rev, January 1, 2003; 83(1): 183 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zong, J. M. Ren, L. H. Young, M. Pypaert, J. Mu, M. J. Birnbaum, and G. I. Shulman AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation PNAS, December 10, 2002; 99(25): 15983 - 15987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ido, D. Carling, and N. Ruderman Hyperglycemia-Induced Apoptosis in Human Umbilical Vein Endothelial Cells: Inhibition by the AMP-Activated Protein Kinase Activation Diabetes, January 1, 2002; 51(1): 159 - 167. [Abstract] [Full Text] [PDF]
|
|