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An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
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Stk24 protects against obesity-associated metabolic disorders by disrupting the NLRP3 inflammasome

Qiang Qin1, Jia'nan Shou1, Mengjie Li1

  • 1Institute of Immunology and Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.

Cell Reports
|May 26, 2021
PubMed

Insights

Serine/threonine protein kinase 24 (Stk24) is reduced in obesity, worsening metabolic disorders. Restoring Stk24 function may treat obesity-related conditions by reducing inflammation.

Area of Science:

  • Metabolic disorders
  • Immunology
  • Obesity research

Background:

  • Adipose tissue macrophages (ATMs) play a critical role in obesity and related metabolic diseases.
  • Understanding the molecular mechanisms regulating ATM function is crucial for developing therapeutic strategies.

Purpose of the Study:

  • To investigate the role of serine/threonine protein kinase 24 (Stk24) in adipose tissue macrophages (ATMs) in the context of obesity and metabolic dysfunction.
  • To elucidate the molecular mechanisms by which Stk24 influences metabolic health.

Main Methods:

  • Analysis of Stk24 expression in ATMs from human subjects and mice under conditions of obesity and high-fat diet (HFD) feeding.
  • Investigation of Stk24 function using Stk24-deficient mice and assessment of metabolic parameters and insulin sensitivity.
  • Exploration of the molecular interaction between Stk24 and NLRP3 inflammasome components in ATMs.

Main Results:

  • Stk24 expression is significantly downregulated in ATMs of obese subjects, individuals with type 2 diabetes, and mice fed an HFD.
  • Glucolipotoxicity was identified as a factor that downregulates Stk24 expression in ATMs.
  • Stk24-deficient mice exhibited exacerbated HFD-induced metabolic disorders and insulin insensitivity.
  • Stk24 directly interacts with NLRP3, inhibiting NLRP3 inflammasome assembly and subsequent interleukin-1β (IL-1β) secretion.
  • Hematopoietic Stk24 deficiency promoted NLRP3 inflammasome activation, worsening metabolic disorders.
  • Human subject data showed a negative correlation between Stk24 expression and body mass index (BMI), glucose, cholesterol, triglycerides, and low-density lipoprotein levels.

Conclusions:

  • Stk24 plays a protective role against obesity-mediated metabolic disorders by regulating ATM inflammatory responses.
  • Stk24 acts as a negative regulator of NLRP3 inflammasome activation in ATMs.
  • Stk24 represents a potential therapeutic target for managing obesity and associated metabolic complications.
Keywords:
NLRP3 inflammasomeStk24adipose tissue macrophagesobesity-associated metabolic disorderserine\threonine protein kinase 24

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