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Salt-inducible kinase 2 regulates TFEB and is required for autophagic flux in adipocytes

Negoita, Florentina LU ; Säll, Johanna LU orcid ; Morén, Björn LU orcid ; Stenkula, Karin LU and Göransson, Olga LU orcid (2019) In Biochemical and Biophysical Research Communications 508(3). p.775-779
Abstract

Dysregulation of autophagy has been observed in obesity and type 2 diabetes. Salt-inducible kinase 2 (SIK2), a member of the AMPK-related kinase family, is downregulated in adipocytes from obese or insulin resistant individuals and was previously demonstrated to regulate autophagy in cancer and normal cell lines. The aim of this study was thus to investigate a potential role of SIK2 in the regulation of adipocyte autophagy. To do so, SIK2 siRNA silencing or SIKs pharmacological inhibition of SIK2 was employed in murine differentiated 3T3-L1 adipocytes and autophagic flux was monitored. Our data indicate that SIK2 is required for both autophagic flux and expression of TFEB, the transcription factor that regulates autophagy, in... (More)

Dysregulation of autophagy has been observed in obesity and type 2 diabetes. Salt-inducible kinase 2 (SIK2), a member of the AMPK-related kinase family, is downregulated in adipocytes from obese or insulin resistant individuals and was previously demonstrated to regulate autophagy in cancer and normal cell lines. The aim of this study was thus to investigate a potential role of SIK2 in the regulation of adipocyte autophagy. To do so, SIK2 siRNA silencing or SIKs pharmacological inhibition of SIK2 was employed in murine differentiated 3T3-L1 adipocytes and autophagic flux was monitored. Our data indicate that SIK2 is required for both autophagic flux and expression of TFEB, the transcription factor that regulates autophagy, in adipocytes. The effect of SIK2 on autophagic flux occurs before the regulation of TFEB protein levels, suggesting different mechanisms whereby SIK2 stimulates autophagy. This study broadens the current knowledge on autophagy regulation and SIK2 function in adipocytes.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adipocytes, Autophagic flux, Autophagy, Salt-inducible kinase 2, TFEB
in
Biochemical and Biophysical Research Communications
volume
508
issue
3
pages
5 pages
publisher
Elsevier
external identifiers
  • pmid:30528240
  • scopus:85059223479
ISSN
0006-291X
DOI
10.1016/j.bbrc.2018.11.177
language
English
LU publication?
yes
id
c9027c17-edb0-4a40-9131-e3dbe3b4b97d
date added to LUP
2019-01-11 08:38:21
date last changed
2024-03-02 16:46:07
@article{c9027c17-edb0-4a40-9131-e3dbe3b4b97d,
  abstract     = {{<p>Dysregulation of autophagy has been observed in obesity and type 2 diabetes. Salt-inducible kinase 2 (SIK2), a member of the AMPK-related kinase family, is downregulated in adipocytes from obese or insulin resistant individuals and was previously demonstrated to regulate autophagy in cancer and normal cell lines. The aim of this study was thus to investigate a potential role of SIK2 in the regulation of adipocyte autophagy. To do so, SIK2 siRNA silencing or SIKs pharmacological inhibition of SIK2 was employed in murine differentiated 3T3-L1 adipocytes and autophagic flux was monitored. Our data indicate that SIK2 is required for both autophagic flux and expression of TFEB, the transcription factor that regulates autophagy, in adipocytes. The effect of SIK2 on autophagic flux occurs before the regulation of TFEB protein levels, suggesting different mechanisms whereby SIK2 stimulates autophagy. This study broadens the current knowledge on autophagy regulation and SIK2 function in adipocytes.</p>}},
  author       = {{Negoita, Florentina and Säll, Johanna and Morén, Björn and Stenkula, Karin and Göransson, Olga}},
  issn         = {{0006-291X}},
  keywords     = {{Adipocytes; Autophagic flux; Autophagy; Salt-inducible kinase 2; TFEB}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{775--779}},
  publisher    = {{Elsevier}},
  series       = {{Biochemical and Biophysical Research Communications}},
  title        = {{Salt-inducible kinase 2 regulates TFEB and is required for autophagic flux in adipocytes}},
  url          = {{http://dx.doi.org/10.1016/j.bbrc.2018.11.177}},
  doi          = {{10.1016/j.bbrc.2018.11.177}},
  volume       = {{508}},
  year         = {{2019}},
}