Document Detail


Regulation of AMP-activated protein kinase by LKB1 and CaMKK in adipocytes.
MedLine Citation:
PMID:  21312243     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AMP-activated protein kinase (AMPK) is a serine/threonine kinase that regulates cellular and whole body energy homeostasis. In adipose tissue, activation of AMPK has been demonstrated in response to a variety of extracellular stimuli. However, the upstream kinase that activates AMPK in adipocytes remains elusive. Previous studies have identified LKB1 as a major AMPK kinase in muscle, liver, and other tissues. In certain cell types, Ca(2+) /calmodulin-dependent protein kinase kinase β (CaMKKβ) has been shown to activate AMPK in response to increases of intracellular Ca(2+) levels. Our aim was to investigate if LKB1 and/or CaMKK function as AMPK kinases in adipocytes. We used adipose tissue and isolated adipocytes from mice in which the expression of LKB1 was reduced to 10-20% of that of wild-type (LKB1 hypomorphic mice). We show that adipocytes from LKB1 hypomorphic mice display a 40% decrease in basal AMPK activity and a decrease of AMPK activity in the presence of the AMPK activator phenformin. We also demonstrate that stimulation of 3T3L1 adipocytes with intracellular [Ca(2+) ]-raising agents results in an activation of the AMPK pathway. The inhibition of CaMKK isoforms, particularly CaMKKβ, by the inhibitor STO-609 or by siRNAs, blocked Ca(2+) -, but not phenformin-, AICAR-, or forskolin-induced activation of AMPK, indicating that CaMKK activated AMPK in response to Ca(2+) . Collectively, we show that LKB1 is required to maintain normal AMPK-signaling in non-stimulated adipocytes and in the presence of phenformin. In addition, we demonstrate the existence of a Ca(2+) /CaMKK signaling pathway that can also regulate the activity of AMPK in adipocytes.
Authors:
Amélie Gormand; Emma Henriksson; Kristoffer Ström; Thomas Elbenhardt Jensen; Kei Sakamoto; Olga Göransson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  112     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-05     Completed Date:  2011-07-20     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1364-75     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
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MeSH Terms
Descriptor/Qualifier:
3T3-L1 Cells
AMP-Activated Protein Kinases / genetics,  metabolism*
Adipocytes / enzymology*
Adipose Tissue / enzymology
Animals
Benzimidazoles / pharmacology
Calcium / metabolism*
Calcium-Calmodulin-Dependent Protein Kinase Kinase / antagonists & inhibitors,  genetics,  metabolism*
Colforsin / pharmacology
Mice
Mice, Knockout
Naphthalimides / pharmacology
Phenformin / pharmacology
Protein-Serine-Threonine Kinases / antagonists & inhibitors,  genetics,  metabolism*
Signal Transduction / genetics
Grant Support
ID/Acronym/Agency:
MC_U127088492//Medical Research Council; //Medical Research Council
Chemical
Reg. No./Substance:
0/Benzimidazoles; 0/Naphthalimides; 0/STO 609; 1F7A44V6OU/Colforsin; DD5K7529CE/Phenformin; EC 2.7.1.-/STK11 protein, human; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Kinase; SY7Q814VUP/Calcium

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


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