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Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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  11. Sphk2 Inhibition Alleviates Chronic Intermittent Hypoxia-induced Inflammation In Adipose Tissue By Decreasing Endoplasmic Reticulum Stress

SPHK2 inhibition alleviates chronic intermittent hypoxia-induced inflammation in adipose tissue by decreasing endoplasmic reticulum stress

Longyi Ran1, Chang Wei1, Xinyu Wang1

  • 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China; State Key Laboratory of Respiratory Health and Multimorbidity.

European Journal of Pharmacology
|June 13, 2025

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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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Investigation of Beige Fat Biology and Metabolism Using the CRISPR SunTag-p65-HSF1 Activation System
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View abstract on PubMed

Summary
This summary is machine-generated.

Obstructive Sleep Apnea (OSA) causes lipid metabolism issues by activating Sphingosine Kinase 2 (SPHK2) and endoplasmic reticulum stress (ERS). Inhibiting SPHK2 may treat these OSA-related metabolic disturbances.

Area of Science:

  • Metabolic disease research
  • Sleep medicine
  • Molecular biology

Background:

  • Obstructive Sleep Apnea (OSA) is linked to cardiovascular and metabolic issues, often involving lipid disturbances and adipose tissue inflammation due to chronic intermittent hypoxia (CIH).
  • The precise molecular mechanisms connecting CIH, lipid metabolism, and adipose tissue inflammation in OSA are not fully understood.

Purpose of the Study:

  • To investigate the roles of Sphingosine Kinase 2 (SPHK2) and endoplasmic reticulum stress (ERS) in CIH-induced lipid metabolic disturbances within adipose tissue.
  • To evaluate the therapeutic potential of targeting SPHK2 and ERS in a mouse model of OSA.

Main Methods:

  • A mouse model of chronic intermittent hypoxia (CIH) was established, exposing mice to normal air (NA) or CIH for 4 or 12 weeks.
  • Systemic lipid levels (triglycerides, total cholesterol, LDL-C) were measured.
Keywords:
(CIH)(ERS)(OSA)(SPHK2)

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  • SPHK2 expression, ERS signaling (PERK-ATF4-CHOP), NLRP3 inflammasome, oxidative stress, and adipocyte apoptosis were assessed in white adipose tissue (epididymal and subcutaneous).
  • Pharmacological interventions using an SPHK2 inhibitor (opaganib) and an ERS inhibitor (4-BPA) were employed, along with an ERS activator (thapsigargin) for contrast.

    • Main Results:

    • CIH exposure significantly increased SPHK2 expression and activated the PERK-ATF4-CHOP pathway in adipose tissue, leading to increased NLRP3 inflammasome, oxidative stress, and adipocyte apoptosis.
    • SPHK2 inhibition with opaganib attenuated CIH-induced ERS, oxidative stress, and inflammation, restoring lipid homeostasis.
    • ERS inhibition with 4-BPA reduced oxidative stress and inflammatory cytokines, alleviating adipose tissue inflammation.
    • ERS activation counteracted the benefits of SPHK2 inhibition, worsening metabolic and inflammatory issues.

    Conclusions:

    • SPHK2 and ERS play critical roles in mediating adipose tissue inflammation and lipid metabolic disturbances associated with CIH in OSA.
    • Pharmacological inhibition of SPHK2 shows promise as a therapeutic strategy for managing lipid metabolic complications in OSA patients.
    Chronic Intermittent Hypoxia
    Endoplasmic Reticulum Stress
    Lipid Metabolism Disturbance
    Obstructive Sleep Apnea
    Sphingosine Kinase 2