Document Detail

AMPK activity is diminished in tissues of IL-6 knockout mice: the effect of exercise.
MedLine Citation:
PMID:  15219849     Owner:  NLM     Status:  MEDLINE    
Following exercise, AMP-activated protein kinase (AMPK) activity is increased several fold in rat liver and adipose tissue as well as muscle; however, the mechanism by which this occurs is not known. Interleukin-6 (IL-6) is released from muscle in large amounts during and after sustained physical activity resulting in up to 100-fold increases in its plasma concentration, from 1-2 ng/ml to 50-100 ng/ml. We report here that incubation with IL-6 (30-120 ng/ml) increases the phosphorylation of AMPK (an indicator of its activation) and that of its target molecule, acetyl CoA carboxylase (ACC), in both extensor digitorum longus muscle and cultured F422a adipocytes. To assess more directly whether IL-6 regulates AMPK in vivo during exercise, measurements were carried out in skeletal muscle, liver, and adipose tissue of 3-month-old IL-6 knockout (IL-6(-/-)) and C57 black control mice. In agreement with previous studies in the rat, in control mice P-AMPK and P-ACC abundance was increased by 30-150% in the three tissues in response to exercise with the greatest increases in skeletal muscle. In contrast, in IL-6(-/-) mice, we found that the abundance of both P-AMPK and P-ACC was lower (60-90%) in muscle and adipose tissue at rest. Also the absolute increases in P-AMPK caused by exercise were diminished compared to those in control mice, although percentage increases were similar. In liver, decreases in P-AMPK and P-ACC in the IL-6(-/-) mice were more modest and the increases in their abundance caused by exercise were indistinguishable from those of control mice. The results indicate that IL-6 can activate AMPK in muscle and adipose tissue, and that this contributes to, but does not fully account for, the increase in AMPK activity in these tissues in response to exercise. They also suggest that a genetic lack of IL-6 is associated with a decrease in AMPK activity.
Meghan Kelly; Charlotte Keller; Paco R Avilucea; Pernille Keller; Zhijun Luo; Xiaoquin Xiang; Mercé Giralt; Juan Hidalgo; Asish K Saha; Bente K Pedersen; Neil B Ruderman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  320     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-28     Completed Date:  2004-08-12     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  449-54     Citation Subset:  IM    
Diabetes Unit, Section of Endocrinology, Boston Medical Center and Departments of Medicine and Physiology, Boston University School of Medicine, Boston, MA 02118, USA.
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MeSH Terms
AMP-Activated Protein Kinases
Adipocytes / enzymology
Interleukin-6 / genetics,  physiology*
Liver / enzymology
Mice, Knockout
Multienzyme Complexes / metabolism*
Muscle, Skeletal / enzymology
Physical Conditioning, Animal*
Protein-Serine-Threonine Kinases / metabolism*
Grant Support
Reg. No./Substance:
0/Interleukin-6; 0/Multienzyme Complexes; EC Protein Kinases; EC Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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