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Peer-reviewedCC BY-NC-NDNature communications

Microglial protein kinase CK2 prevents obesity in mice potentially through NLRP3 inflammasome activation.

  • Ji-Won Lee1
  • Nayoun Kim1
  • Seolsong Kim1
  • Seokjae Park1,2
  • Hyeri Nam1
  • Younghwan Lee1
  • Seohyeon Hwang1
  • Yeim Lee1
  • Sehee Ha1
  • Wonkeon Koo1
  • Eun-Kyoung Kim3,4
  • Seong-Woon Yu5
5 affiliations
  1. 1Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea.
  2. 2Neurometabolomics Research Center, DGIST, Daegu, Republic of Korea.
  3. 3Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea. [email protected].
  4. 4Neurometabolomics Research Center, DGIST, Daegu, Republic of Korea. [email protected].
  5. 5Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea. [email protected].
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Abstract

Protein kinase CK2 plays an important role in the regulation of metabolism and obesity. However, the metabolic role of CK2 and its substrates in the brain remain largely unknown. Here, we show that microglial CK2 is required for metabolic homeostasis through ASC phosphorylation and subsequent NLRP3 inflammasome-mediated interleukin (IL)-18 maturation and release. Mice with microglia-specific, inducible deletion of CK2 regulatory subunit β (CK2β) showed obese phenotypes with weight gain, abnormal glucose homeostasis, and decreased energy expenditure. At the molecular level, CK2 phosphorylated ASC at T154, and this phosphorylation was essential for ASC aggregation and NLRP3 inflammasome activation. Microglial deletion of CK2β decreased central production of IL-18, mirroring the obese phenotypes of mice lacking IL-18 signaling. Our results suggest that the microglial CK2-ASC-NLRP3 axis underlies the central regulation of metabolic homeostasis and prevents obesity through processing and secretion of IL-18. Nevertheless, a gap remains between these molecular mechanistic findings and the observed in vivo behavioral and metabolic phenotypes, highlighting the need for future systems-level analyses to fully delineate the broader substrate landscape of CK2 and to integrate the functional outcomes of CK2 deficiency in microglia with in vivo phenotypes.

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Cite

BibTeXRIS
BibTeX
@article{lee2026microglial,
  title = {{Microglial protein kinase CK2 prevents obesity in mice potentially through NLRP3 inflammasome activation.}},
  author = {Ji-Won Lee and Nayoun Kim and Seolsong Kim and Seokjae Park and Hyeri Nam and Younghwan Lee and Seohyeon Hwang and Yeim Lee and Sehee Ha and Wonkeon Koo and Eun-Kyoung Kim and Seong-Woon Yu},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77895-1},
  url = {https://europepmc.org/article/MED/42907441},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Microglial protein kinase CK2 prevents obesity in mice potentially through NLRP3 inflammasome activation.
AU  - Ji-Won Lee
AU  - Nayoun Kim
AU  - Seolsong Kim
AU  - Seokjae Park
AU  - Hyeri Nam
AU  - Younghwan Lee
AU  - Seohyeon Hwang
AU  - Yeim Lee
AU  - Sehee Ha
AU  - Wonkeon Koo
AU  - Eun-Kyoung Kim
AU  - Seong-Woon Yu
PY  - 2026
DA  - 2026/09/22
JO  - Nature communications
DO  - 10.1038/s41467-026-77895-1
UR  - https://europepmc.org/article/MED/42907441
AB  - Protein kinase CK2 plays an important role in the regulation of metabolism and obesity. However, the metabolic role of CK2 and its substrates in the brain remain largely unknown. Here, we show that microglial CK2 is required for metabolic homeostasis through ASC phosphorylation and subsequent NLRP3 inflammasome-mediated interleukin (IL)-18 maturation and release. Mice with microglia-specific, inducible deletion of CK2 regulatory subunit β (CK2β) showed obese phenotypes with weight gain, abnormal glucose homeostasis, and decreased energy expenditure. At the molecular level, CK2 phosphorylated ASC at T154, and this phosphorylation was essential for ASC aggregation and NLRP3 inflammasome activation. Microglial deletion of CK2β decreased central production of IL-18, mirroring the obese phenotypes of mice lacking IL-18 signaling. Our results suggest that the microglial CK2-ASC-NLRP3 axis underlies the central regulation of metabolic homeostasis and prevents obesity through processing and secretion of IL-18. Nevertheless, a gap remains between these molecular mechanistic findings and the observed in vivo behavioral and metabolic phenotypes, highlighting the need for future systems-level analyses to fully delineate the broader substrate landscape of CK2 and to integrate the functional outcomes of CK2 deficiency in microglia with in vivo phenotypes.
SN  - 2041-1723
ER  -