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: 292/1/E196    most recent 00366.2006v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire 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.

Skeletal muscle and heart LKB1 deficiency causes decreased voluntary running and reduced muscle mitochondrial marker enzyme expression in mice

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

Submitted 21 July 2006 ; accepted in final form 18 August 2006

LKB1 has been identified as a component of the major upstream kinase of AMP-activated protein kinase (AMPK) in skeletal muscle. To investigate the roles of LKB1 in skeletal muscle, we used muscle-specific LKB1 knockout (MLKB1KO) mice that exhibit low expression of LKB1 in heart and skeletal muscle, but not in other tissues. The importance of LKB1 in muscle physiology was demonstrated by the observation that electrical stimulation of the muscle in situ increased AMPK phosphorylation and activity in the wild-type (WT) but not in the muscle-specific LKB1KO mice. Likewise, phosphorylation of acetyl-CoA carboxylase (ACC) was markedly attenuated in the KO mice. The LKB1KO mice had difficulty running on the treadmill and exhibited marked reduction in distance run in voluntary running wheels over a 3-wk period (5.9 ± 0.9 km/day for WT vs. 1.7 ± 0.7 km/day for MLKB1KO mice). The MLKB1KO mice anesthetized at rest exhibited significantly decreased phospho-AMPK and phospho-ACC compared with WT mice. KO mice exhibited lower levels of mitochondrial protein expression in the red and white regions of the quadriceps. These observations, along with previous observations from other laboratories, clearly demonstrate that LKB1 is the major upstream kinase in skeletal muscle and that it is essential for maintaining mitochondrial marker proteins in skeletal muscle. These data provide evidence for a critical role of LKB1 in muscle physiology, one of which is maintaining basal levels of mitochondrial oxidative enzymes. Capacity for voluntary running is compromised with muscle and heart LKB1 deficiency.

adenosine 3'-cyclic monophosphate-activated protein kinase; muscle specific LKB1 knockout mouse; muscle mitochondria; citrate synthase

This article has been cited by other articles:

				G. R. Steinberg and B. E. Kemp AMPK in Health and Disease Physiol Rev, July 1, 2009; 89(3): 1025 - 1078. [Abstract] [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, C. A. Fick, and S. E. Gordon AMPK activation attenuates S6K1, 4E-BP1, and eEF2 signaling responses to high-frequency electrically stimulated skeletal muscle contractions J Appl Physiol, March 1, 2008; 104(3): 625 - 632. [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]

				D. M. Thomson, J. D. Brown, N. Fillmore, B. M. Condon, H-J. Kim, J. R. Barrow, and W. W. Winder LKB1 and the regulation of malonyl-CoA and fatty acid oxidation in muscle Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1572 - E1579. [Abstract] [Full Text] [PDF]

				S. Schiaffino, M. Sandri, and M. Murgia Activity-Dependent Signaling Pathways Controlling Muscle Diversity and Plasticity Physiology, August 1, 2007; 22(4): 269 - 278. [Abstract] [Full Text] [PDF]

				T. E. Jensen, A. J. Rose, Y. Hellsten, J. F. P. Wojtaszewski, and E. A. Richter Caffeine-induced Ca2+ release increases AMPK-dependent glucose uptake in rodent soleus muscle Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E286 - E292. [Abstract] [Full Text] [PDF]

				T. E. Jensen, A. J. Rose, S. B. Jorgensen, N. Brandt, P. Schjerling, J. F. P. Wojtaszewski, and E. A. Richter Possible CaMKK-dependent regulation of AMPK phosphorylation and glucose uptake at the onset of mild tetanic skeletal muscle contraction Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1308 - E1317. [Abstract] [Full Text] [PDF]