LKB1 signalling attenuates early events of adipogenesis and responds to adipogenic cues.
Gormand, Amelie LU ; Berggreen, Christine LU ; Amar, Lahouari LU ; Henricksson, Emma ; Lund, Ingrid LU ; Albinsson, Sebastian LU and Göransson, Olga LU
(2014)
In Journal of Molecular Endocrinology
53(1).
p.117-130
- Abstract
- cAMP-response element-binding protein (CREB) is required for the induction of adipogenic transcription factors such as CCAAT/enhancer-binding proteins (C/EBPs). Interestingly, it is known from other tissues that LKB1 and its substrates AMP-activated protein kinase (AMPK) and salt-inducible kinases (SIKs), negatively regulate gene expression by phosphorylating the CREB co-activator CRTC2 and class IIa histone deacetylases (HDACs), which results in their exclusion from the nucleus where they co-activate or inhibit their targets. In this study, we show that AMPK/SIK signalling is acutely attenuated during adipogenic differentiation of 3T3-L1 preadipocytes, which coincides with dephosphorylation and nuclear translocation of CRTC2 and HDAC4.... (More)
- cAMP-response element-binding protein (CREB) is required for the induction of adipogenic transcription factors such as CCAAT/enhancer-binding proteins (C/EBPs). Interestingly, it is known from other tissues that LKB1 and its substrates AMP-activated protein kinase (AMPK) and salt-inducible kinases (SIKs), negatively regulate gene expression by phosphorylating the CREB co-activator CRTC2 and class IIa histone deacetylases (HDACs), which results in their exclusion from the nucleus where they co-activate or inhibit their targets. In this study, we show that AMPK/SIK signalling is acutely attenuated during adipogenic differentiation of 3T3-L1 preadipocytes, which coincides with dephosphorylation and nuclear translocation of CRTC2 and HDAC4. When subjected to differentiation, 3T3-L1 preadipocytes in which LKB1 expression was stably reduced using shRNA (LKB1-shRNA), as well as LKB1 knockout mouse embryonic fibroblasts (LKB1-/- MEFs), differentiated more readily into adipocyte-like cells and accumulated more triglycerides compared to scrambled-shRNA 3T3-L1 cells or Wt MEFs. In addition, the phosphorylation of CRTC2 and HDAC4 was reduced, and the mRNA expression of adipogenic transcription factors C/EBPα, peroxisome proliferator-activated receptor γ (PPARγ) and adipocyte-specific proteins such as hormone sensitive lipase (HSL), fatty acid synthase (FAS), aP2, Glut4 and adiponectin was increased in the absence of LKB1. The mRNA and protein expression of CHOP-10, a dominant negative member of the C/EBP family, was reduced in LKB1 shRNA expressing cells, providing a potential mechanism for the up-regulation of Pparg and Cebpa. These results support the hypothesis that LKB1 signalling keeps preadipocytes in their non-differentiated form. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4452580
- author
- Gormand, Amelie
LU
; Berggreen, Christine
LU
; Amar, Lahouari
LU
; Henricksson, Emma
; Lund, Ingrid
LU
; Albinsson, Sebastian
LU
and Göransson, Olga
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Molecular Endocrinology
- volume
- 53
- issue
- 1
- pages
- 117 - 130
- publisher
- Society for Endocrinology
- external identifiers
-
- pmid:24859970
- wos:000345617800018
- scopus:84904017128
- ISSN
- 1479-6813
- DOI
- 10.1530/JME-13-0296
- language
- English
- LU publication?
- yes
- id
- d32f2e8e-a6a2-4bb9-b17c-346f4ef811e9 (old id 4452580)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24859970?dopt=Abstract
- date added to LUP
- 2016-04-01 10:11:56
- date last changed
- 2024-04-07 03:43:07
@article{d32f2e8e-a6a2-4bb9-b17c-346f4ef811e9,
abstract = {{cAMP-response element-binding protein (CREB) is required for the induction of adipogenic transcription factors such as CCAAT/enhancer-binding proteins (C/EBPs). Interestingly, it is known from other tissues that LKB1 and its substrates AMP-activated protein kinase (AMPK) and salt-inducible kinases (SIKs), negatively regulate gene expression by phosphorylating the CREB co-activator CRTC2 and class IIa histone deacetylases (HDACs), which results in their exclusion from the nucleus where they co-activate or inhibit their targets. In this study, we show that AMPK/SIK signalling is acutely attenuated during adipogenic differentiation of 3T3-L1 preadipocytes, which coincides with dephosphorylation and nuclear translocation of CRTC2 and HDAC4. When subjected to differentiation, 3T3-L1 preadipocytes in which LKB1 expression was stably reduced using shRNA (LKB1-shRNA), as well as LKB1 knockout mouse embryonic fibroblasts (LKB1-/- MEFs), differentiated more readily into adipocyte-like cells and accumulated more triglycerides compared to scrambled-shRNA 3T3-L1 cells or Wt MEFs. In addition, the phosphorylation of CRTC2 and HDAC4 was reduced, and the mRNA expression of adipogenic transcription factors C/EBPα, peroxisome proliferator-activated receptor γ (PPARγ) and adipocyte-specific proteins such as hormone sensitive lipase (HSL), fatty acid synthase (FAS), aP2, Glut4 and adiponectin was increased in the absence of LKB1. The mRNA and protein expression of CHOP-10, a dominant negative member of the C/EBP family, was reduced in LKB1 shRNA expressing cells, providing a potential mechanism for the up-regulation of Pparg and Cebpa. These results support the hypothesis that LKB1 signalling keeps preadipocytes in their non-differentiated form.}},
author = {{Gormand, Amelie and Berggreen, Christine and Amar, Lahouari and Henricksson, Emma and Lund, Ingrid and Albinsson, Sebastian and Göransson, Olga}},
issn = {{1479-6813}},
language = {{eng}},
number = {{1}},
pages = {{117--130}},
publisher = {{Society for Endocrinology}},
series = {{Journal of Molecular Endocrinology}},
title = {{LKB1 signalling attenuates early events of adipogenesis and responds to adipogenic cues.}},
url = {{https://lup.lub.lu.se/search/files/1644246/7852910.pdf}},
doi = {{10.1530/JME-13-0296}},
volume = {{53}},
year = {{2014}},
}