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

Amelie Gormand, Emma Henriksson, Kristoffer Ström, Thomas Elbenhardt Jensen, Kei Sakamoto, Olga Göransson

Research output: Contribution to journalArticlepeer-review

57 Citations (SciVal)


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.
Original languageEnglish
Pages (from-to)1364-1375
JournalJournal of Cellular Biochemistry
Publication statusPublished - 2011

Subject classification (UKÄ)

  • Basic Medicine
  • Endocrinology and Diabetes


Dive into the research topics of 'Regulation of AMP-activated protein kinase by LKB1 and CaMKK in adipocytes.'. Together they form a unique fingerprint.

Cite this