Impact of Glucose Fluctuations on the Human Epicardial Adipocyte-Derived Paracrine Secretome

Abstract

BACKGROUND: Because glucose fluctuations (GFs) are significantly associated with poor cardiovascular outcomes in patients with diabetes mellitus, we investigated their potential impact on the paracrine effects of human epicardial adipocytes on cardiomyocytes. METHODS AND RESULTS: Human epicardial adipose tissue (EAT) biopsies and isolated EAT-derived adipocytes were used to evaluate the direct impact of GFs. Mature adipocytes were exposed to media containing normal glucose (NG), high glucose (HG), or GFs. GFs altered the expression of 595 differentially expressed genes with an effect size greater than ±50% and a statistically significant difference (P<0.05) in human epicardial adipocytes, whereas continuous HG altered the expression of only 182 genes. Among the genes affected exclusively by GFs, the top 3 most affected were IL1β, IL33, and IL8. Coculture of human induced pluripotent stem cell-derived atrial cardiomyocytes and adipocytes treated with NG, HG, or GFs revealed that adipocytes exposed to GFs markedly increased oxidative stress in cardiomyocytes through paracrine effects. In a real-world clinical association study, IL1β mRNA expression in human EAT showed a significant positive correlation with the severity of GFs during hospitalization and with oxidative stress in the left atrial myocardium. CONCLUSIONS: GFs adversely affect the paracrine secretome profile of human epicardial adipocytes. IL1β may be a critical epicardial adipocyte-derived adipokine that is upregulated by GFs.

Glucose Fluctuations and Epicardial Adipose Tissue ― A New Paradigm for Diabetic Myocardial Damage ―
Takeshi Soeki
Circulation Journal25 Sep 2026Peer-reviewedCC BY-NC-NDFull textCardiovascular medicineJ-STAGE
Paracrine bone-derived senescent secretome is associated with spatially patterned extracellular matrix remodeling and altered biomechanics in human brain organoids
Chanul Kim, Luke D Ofria, Hossein Shaygani +6
Stem Cells12 Oct 2026Peer-reviewedCC BY-NC 4.0Full textPhysiologyPMC
SMPD3 suppresses oligodendroglioma growth via dual autocrine-paracrine roles
Fermisk Saleh, Anjali Balakrishnan, Lata Adnani +25
Communications Biology1 Jun 2026Peer-reviewedCC BYFull textHuman geneticsDOAJ
Transatrial air-assisted epicardial ventricular tachycardia ablation for hypertrophic cardiomyopathy and management of postprocedural right atrial thrombus.
İbrahim Etem Dural, Mehmet Özgeyik, Ramazan Anıl Eşki +1
HeartRhythm case reports8 Jul 2026Peer-reviewedCC BY-NC-NDFull textCardiovascular medicineEurope PMC
Thirty years of percutaneous epicardial access: reflections on the evolution of ventricular tachycardia substrate mapping and ablation
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology1 Oct 2026Peer-reviewedCC BYFull textCardiovascular medicineEurope PMC

Cite

BibTeX RIS

BibTeX

@article{takano2026impact,
  title = {{Impact of Glucose Fluctuations on the Human Epicardial Adipocyte-Derived Paracrine Secretome}},
  author = {Masayuki Takano and Hidekazu Kondo and Taisuke Harada and Masaki Takahashi and Yumi Ishii and Hirochika Yamasaki and Takashi Shuto and Yasushi Teshima and Tomoyuki Wada and Kunio Yufu and Hidenori Sako and Hirofumi Anai and Shinji Miyamoto and Naohiko Takahashi},
  journal = {Circulation Journal},
  year = {2026},
  month = sep,
  doi = {10.1253/circj.cj-26-0082},
  url = {https://www.jstage.jst.go.jp/article/circj/90/10/90_CJ-26-0082/_article},
  note = {CC BY-NC-ND},
}

RIS

TY  - JOUR
TI  - Impact of Glucose Fluctuations on the Human Epicardial Adipocyte-Derived Paracrine Secretome
AU  - Masayuki Takano
AU  - Hidekazu Kondo
AU  - Taisuke Harada
AU  - Masaki Takahashi
AU  - Yumi Ishii
AU  - Hirochika Yamasaki
AU  - Takashi Shuto
AU  - Yasushi Teshima
AU  - Tomoyuki Wada
AU  - Kunio Yufu
AU  - Hidenori Sako
AU  - Hirofumi Anai
AU  - Shinji Miyamoto
AU  - Naohiko Takahashi
PY  - 2026
DA  - 2026/09/25
JO  - Circulation Journal
DO  - 10.1253/circj.cj-26-0082
UR  - https://www.jstage.jst.go.jp/article/circj/90/10/90_CJ-26-0082/_article
AB  - BACKGROUND: Because glucose fluctuations (GFs) are significantly associated with poor cardiovascular outcomes in patients with diabetes mellitus, we investigated their potential impact on the paracrine effects of human epicardial adipocytes on cardiomyocytes. METHODS AND RESULTS: Human epicardial adipose tissue (EAT) biopsies and isolated EAT-derived adipocytes were used to evaluate the direct impact of GFs. Mature adipocytes were exposed to media containing normal glucose (NG), high glucose (HG), or GFs. GFs altered the expression of 595 differentially expressed genes with an effect size greater than ±50% and a statistically significant difference (P<0.05) in human epicardial adipocytes, whereas continuous HG altered the expression of only 182 genes. Among the genes affected exclusively by GFs, the top 3 most affected were IL1β, IL33, and IL8. Coculture of human induced pluripotent stem cell-derived atrial cardiomyocytes and adipocytes treated with NG, HG, or GFs revealed that adipocytes exposed to GFs markedly increased oxidative stress in cardiomyocytes through paracrine effects. In a real-world clinical association study, IL1β mRNA expression in human EAT showed a significant positive correlation with the severity of GFs during hospitalization and with oxidative stress in the left atrial myocardium. CONCLUSIONS: GFs adversely affect the paracrine secretome profile of human epicardial adipocytes. IL1β may be a critical epicardial adipocyte-derived adipokine that is upregulated by GFs.
SN  - 1347-4820
SN  - 1346-9843
ER  -

Abstract

Related

Cite