Regulation of AMP-activated protein kinase by LKB1 and CaMKK in adipocytes.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1831942
- author
- Gormand, Amelie LU ; Henriksson, Emma LU ; Ström, Kristoffer LU ; Jensen, Thomas Elbenhardt ; Sakamoto, Kei and Göransson, Olga LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- 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
- id
- 4e69ecd9-fb9f-4a72-b2c7-5868b4e06433 (old id 1831942)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21312243?dopt=Abstract
- date added to LUP
- 2016-04-04 08:16:11
- date last changed
- 2024-02-27 18:55:50
@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}}, doi = {{10.1002/jcb.23053}}, volume = {{112}}, year = {{2011}}, }