HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/E1572    most recent 00371.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Thomson, D. M. Articles by Winder, W. W. Search for Related Content PubMed PubMed Citation Articles by Thomson, D. M. Articles by Winder, W. W.

LKB1 and the regulation of malonyl-CoA and fatty acid oxidation in muscle

Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah

Submitted 14 June 2007 ; accepted in final form 3 October 2007

5'-AMP-activated protein kinase (AMPK), by way of its inhibition of acetyl-CoA carboxylase (ACC), plays an important role in regulating malonyl-CoA levels and the rate of fatty acid oxidation in skeletal and cardiac muscle. In these tissues, LKB1 is the major AMPK kinase and is therefore critical for AMPK activation. The purpose of this study was to determine how the lack of muscle LKB1 would affect malonyl-CoA levels and/or fatty-acid oxidation. Comparing wild-type (WT) and skeletal/cardiac muscle-specific LKB1 knockout (KO) mice, we found that the 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR)-stimulated decrease in malonyl-CoA levels in WT heart and quadriceps muscles was entirely dependent on the presence of LKB1, as was the AICAR-induced increase in fatty-acid oxidation in EDL muscles in vitro, since these responses were not observed in KO mice. Likewise, the decrease in malonyl-CoA levels after muscle contraction was attenuated in KO gastrocnemius muscles, suggesting that LKB1 plays an important role in promoting the inhibition of ACC, likely by activation of AMPK. However, since ACC phosphorylation still increased and malonyl-CoA levels decreased in KO muscles (albeit not to the levels observed in WT mice), whereas AMPK phosphorylation was entirely unresponsive, LKB1/AMPK signaling cannot be considered the sole mechanism for inhibiting ACC during and after muscle activity. Regardless, our results suggest that LKB1 is an important regulator of malonyl-CoA levels and fatty acid oxidation in skeletal muscle.

5'-AMP-activated protein kinase; acetyl-coenzyne A carboxylase; 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside; electric stimulation; muscle contraction

This article has been cited by other articles:

				B. Egan and J. R. Zierath Hunting for the SNARK in metabolic disease Am J Physiol Endocrinol Metab, May 1, 2009; 296(5): E969 - E972. [Full Text] [PDF]

				D.M. Thomson, J.D. Brown, N. Fillmore, S.K. Ellsworth, D. L. Jacobs, W.W. Winder, C.A. Fick, and S.E. Gordon AMP-activated protein kinase response to contractions and treatment with the AMPK activator AICAR in young adult and old skeletal muscle J. Physiol., May 1, 2009; 587(9): 2077 - 2086. [Abstract] [Full Text] [PDF]

				N. Dzamko, J. D. Schertzer, J. G. Ryall, R. Steel, S. L. Macaulay, S. Wee, Z.-P. Chen, B. J. Michell, J. S. Oakhill, M. J. Watt, et al. AMPK-independent pathways regulate skeletal muscle fatty acid oxidation J. Physiol., December 1, 2008; 586(23): 5819 - 5831. [Abstract] [Full Text] [PDF]

				D. J. Branvold, D. R. Allred, D. J. Beckstead, H. J. Kim, N. Fillmore, B. M. Condon, J. D. Brown, S. N. Sudweeks, D. M. Thomson, and W. W. Winder Thyroid hormone effects on LKB1, MO25, phospho-AMPK, phospho-CREB, and PGC-1{alpha} in rat muscle J Appl Physiol, October 1, 2008; 105(4): 1218 - 1227. [Abstract] [Full Text] [PDF]

				D. M. Thomson, S. T. Herway, N. Fillmore, H. Kim, J. D. Brown, J. R. Barrow, and W. W. Winder AMP-activated protein kinase phosphorylates transcription factors of the CREB family J Appl Physiol, February 1, 2008; 104(2): 429 - 438. [Abstract] [Full Text] [PDF]