Mechanism of TNFα-induced downregulation of salt-inducible kinase 2 in adipocytes
Vaváková, Magdaléna LU ; Hofwimmer, Kaisa ; Laurencikiene, Jurga and Göransson, Olga LU
(2023)
In Scientific Reports
13(1).
- Abstract
Salt-inducible kinase 2 (SIK2) is highly expressed in white adipocytes, but downregulated in individuals with obesity and insulin resistance. These conditions are often associated with a low-grade inflammation in adipose tissue. We and others have previously shown that SIK2 is downregulated by tumor necrosis factor α (TNFα), however, involvement of other pro-inflammatory cytokines, or the mechanisms underlying TNFα-induced SIK2 downregulation, remain to be elucidated. In this study we have shown that TNFα downregulates SIK2 protein expression not only in 3T3L1- but also in human in vitro differentiated adipocytes. Furthermore, monocyte chemoattractant protein-1 and interleukin (IL)-1β, but not IL-6, might also contribute to SIK2... (More)
Salt-inducible kinase 2 (SIK2) is highly expressed in white adipocytes, but downregulated in individuals with obesity and insulin resistance. These conditions are often associated with a low-grade inflammation in adipose tissue. We and others have previously shown that SIK2 is downregulated by tumor necrosis factor α (TNFα), however, involvement of other pro-inflammatory cytokines, or the mechanisms underlying TNFα-induced SIK2 downregulation, remain to be elucidated. In this study we have shown that TNFα downregulates SIK2 protein expression not only in 3T3L1- but also in human in vitro differentiated adipocytes. Furthermore, monocyte chemoattractant protein-1 and interleukin (IL)-1β, but not IL-6, might also contribute to SIK2 downregulation during inflammation. We observed that TNFα-induced SIK2 downregulation occurred also in the presence of pharmacological inhibitors against several kinases involved in inflammation, namely c-Jun N-terminal kinase, mitogen activated protein kinase kinase 1, p38 mitogen activated protein kinase or inhibitor of nuclear factor kappa-B kinase (IKK). However, IKK may be involved in SIK2 regulation as we detected an increase of SIK2 when inhibiting IKK in the absence of TNFα. Increased knowledge about inflammation-induced downregulation of SIK2 could ultimately be used to develop strategies for the reinstalment of SIK2 expression in insulin resistance.
(Less)
- author
- Vaváková, Magdaléna
LU
; Hofwimmer, Kaisa
; Laurencikiene, Jurga
and Göransson, Olga
LU
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 13
- issue
- 1
- article number
- 10559
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:37386070
- scopus:85164023563
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-023-37340-5
- language
- English
- LU publication?
- yes
- id
- 5c5a40f6-7ddc-4ac9-b081-f7f5fb47c3cf
- date added to LUP
- 2023-08-29 15:28:04
- date last changed
- 2024-04-20 02:10:02
@article{5c5a40f6-7ddc-4ac9-b081-f7f5fb47c3cf,
abstract = {{<p>Salt-inducible kinase 2 (SIK2) is highly expressed in white adipocytes, but downregulated in individuals with obesity and insulin resistance. These conditions are often associated with a low-grade inflammation in adipose tissue. We and others have previously shown that SIK2 is downregulated by tumor necrosis factor α (TNFα), however, involvement of other pro-inflammatory cytokines, or the mechanisms underlying TNFα-induced SIK2 downregulation, remain to be elucidated. In this study we have shown that TNFα downregulates SIK2 protein expression not only in 3T3L1- but also in human in vitro differentiated adipocytes. Furthermore, monocyte chemoattractant protein-1 and interleukin (IL)-1β, but not IL-6, might also contribute to SIK2 downregulation during inflammation. We observed that TNFα-induced SIK2 downregulation occurred also in the presence of pharmacological inhibitors against several kinases involved in inflammation, namely c-Jun N-terminal kinase, mitogen activated protein kinase kinase 1, p38 mitogen activated protein kinase or inhibitor of nuclear factor kappa-B kinase (IKK). However, IKK may be involved in SIK2 regulation as we detected an increase of SIK2 when inhibiting IKK in the absence of TNFα. Increased knowledge about inflammation-induced downregulation of SIK2 could ultimately be used to develop strategies for the reinstalment of SIK2 expression in insulin resistance.</p>}},
author = {{Vaváková, Magdaléna and Hofwimmer, Kaisa and Laurencikiene, Jurga and Göransson, Olga}},
issn = {{2045-2322}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Mechanism of TNFα-induced downregulation of salt-inducible kinase 2 in adipocytes}},
url = {{http://dx.doi.org/10.1038/s41598-023-37340-5}},
doi = {{10.1038/s41598-023-37340-5}},
volume = {{13}},
year = {{2023}},
}