Document Detail

LKB1 Regulates Lipid Oxidation During Exercise Independently of AMPK.
MedLine Citation:
PMID:  23349504     Owner:  NLM     Status:  Publisher    
Lipid metabolism is important for health and insulin action, yet the fundamental process of regulating lipid metabolism during muscle contraction is incompletely understood. Here, we show that LKB1 muscle-specific knockout (LKB1 MKO) mice display decreased fatty acid (FA) oxidation during treadmill exercise. LKB1 MKO mice also show decreased muscle SIK3 activity, increased histone deacetylase 4 expression, decreased NAD(+) concentration and SIRT1 activity, and decreased expression of genes involved in FA oxidation. In AMPKα2 KO mice, substrate use was similar to that in WT mice, which excluded that decreased FA oxidation in LKB1 MKO mice was due to decreased AMPKα2 activity. Additionally, LKB1 MKO muscle demonstrated decreased FA oxidation in vitro. A markedly decreased phosphorylation of TBC1D1, a proposed regulator of FA transport, and a low CoA content could contribute to the low FA oxidation in LKB1 MKO. LKB1 deficiency did not reduce muscle glucose uptake or oxidation during exercise in vivo, excluding a general impairment of substrate use during exercise in LKB1 MKO mice. Our findings demonstrate that LKB1 is a novel molecular regulator of major importance for FA oxidation but not glucose uptake in muscle during exercise.
Jacob Jeppesen; Stine J Maarbjerg; Andreas B Jordy; Andreas M Fritzen; Christian Pehmøller; Lykke Sylow; Annette Karen Serup; Niels Jessen; Kasper Thorsen; Clara Prats; Klaus Qvortrup; Jason R B Dyck; Roger W Hunter; Kei Sakamoto; David M Thomson; Peter Schjerling; Jørgen F P Wojtaszewski; Erik A Richter; Bente Kiens
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  Diabetes     Volume:  -     ISSN:  1939-327X     ISO Abbreviation:  Diabetes     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
August Krogh Centre and Molecular Physiology Group, Department of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark.
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