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Regulation of AMP-activated protein kinase by LKB1 and CaMKK in adipocytes.

Gormand, Amelie LU ; Henriksson, Emma LU ; Ström, Kristoffer LU ; Jensen, Thomas Elbenhardt; Sakamoto, Kei and Göransson, Olga LU (2011) In Journal of Cellular Biochemistry 112. p.1364-1375
Abstract
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 (CaMKK) β has been shown to activate AMPK in response to increase 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... (More)
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 (CaMKK) β has been shown to activate AMPK in response to increase 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-signalling in non-stimulated adipocytes and in the presence of phenformin. In addition, we demonstrate the existence of a Ca(2+) /CaMKK signalling pathway that can also regulate the activity of AMPK in adipocytes. J. Cell. Biochem. © 2011 Wiley-Liss, Inc. (Less)
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organization
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type
Contribution to journal
publication status
published
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in
Journal of Cellular Biochemistry
volume
112
pages
1364 - 1375
publisher
Wiley-Blackwell
external identifiers
  • wos:000289361900015
  • pmid:21312243
  • scopus:79953703435
ISSN
0730-2312
DOI
10.1002/jcb.23053
language
English
LU publication?
yes
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4e69ecd9-fb9f-4a72-b2c7-5868b4e06433 (old id 1831942)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21312243?dopt=Abstract
date added to LUP
2011-03-01 14:45:32
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2017-09-17 08:16:19
@article{4e69ecd9-fb9f-4a72-b2c7-5868b4e06433,
  abstract     = {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 (CaMKK) β has been shown to activate AMPK in response to increase 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-signalling in non-stimulated adipocytes and in the presence of phenformin. In addition, we demonstrate the existence of a Ca(2+) /CaMKK signalling pathway that can also regulate the activity of AMPK in adipocytes. J. Cell. Biochem. © 2011 Wiley-Liss, Inc.},
  author       = {Gormand, Amelie and Henriksson, Emma and Ström, Kristoffer and Jensen, Thomas Elbenhardt and Sakamoto, Kei and Göransson, Olga},
  issn         = {0730-2312},
  language     = {eng},
  pages        = {1364--1375},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Cellular Biochemistry},
  title        = {Regulation of AMP-activated protein kinase by LKB1 and CaMKK in adipocytes.},
  url          = {http://dx.doi.org/10.1002/jcb.23053},
  volume       = {112},
  year         = {2011},
}