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  • Mechanism of TNFα-induced downregulation of salt-inducible kinase 2 in adipocytes.

Mechanism of TNFα-induced downregulation of salt-inducible kinase 2 in adipocytes.

Scientific reports (2023-06-30)
Magdaléna Vaváková, Kaisa Hofwimmer, Jurga Laurencikiene, Olga Göransson
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 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.

MATERIALS
Product Number
Brand
Product Description

Millipore
Protease Inhibitor Cocktail Set III, EDTA-Free, Protease inhibitor cocktail III, EDTA-free for inhibiting aspartic, cysteine, and serine proteases as well as aminopeptidases in mammalian cells and tissues.
Pricing and availability is not currently available.
Sigma-Aldrich
3-Isobutyl-1-methylxanthine, ≥99%, BioUltra
Pricing and availability is not currently available.
Sigma-Aldrich
IL-6 from mouse, Animal-component free, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC)
Pricing and availability is not currently available.
Sigma-Aldrich
JE/MCP-1 (CCL2) from mouse, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture
Pricing and availability is not currently available.