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  3. Peroxisomal dysfunction in cardiac adipose tissue is involved in obesity-associated cardiac hypertrophy

Peroxisomal dysfunction in cardiac adipose tissue is involved in obesity-associated cardiac hypertrophy

  • J Adv Res. 2025 Nov 20:S2090-1232(25)00927-0. doi: 10.1016/j.jare.2025.11.031.
Gahee Song 1,  Se Jin Jung 2,  Wenjun Jiao 2,  Woo Yong Park 1,  Yunju Jo 3,  Ja Yeon Park 2,  Seong-Kyu Choe 4,  In Jin Ha 5,  Peter K Kim 6,  Dongryeol Ryu 3,  Kuk Hui Son 7,  Hyun Jeong Kwak 8,  Jae-Young Um 9
Affiliations

Affiliations

  • 1 Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, the Republic of Korea; Kyung Hee Institute of Convergence Korean Medicine, Kyung Hee University, Seoul, the Republic of Korea.
  • 2 Kyung Hee Institute of Convergence Korean Medicine, Kyung Hee University, Seoul, the Republic of Korea; Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, the Republic of Korea.
  • 3 Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, the Republic of Korea.
  • 4 Department of Microbiology, Wonkwang University School of Medicine, Iksan, the Republic of Korea.
  • 5 Korean Medicine Clinical Trial Center (K-CTC), Kyung Hee University Korean Medicine Hospital, Seoul, the Republic of Korea.
  • 6 Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, the Republic of Korea; Department of Biochemistry, University of Toronto, Toronto, Canada.
  • 7 Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon, the Republic of Korea. Electronic address: [email protected].
  • 8 Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul, the Republic of Korea. Electronic address: [email protected].
  • 9 Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, the Republic of Korea; Kyung Hee Institute of Convergence Korean Medicine, Kyung Hee University, Seoul, the Republic of Korea; Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, the Republic of Korea. Electronic address: [email protected].
PMID: 41274637 DOI: 10.1016/j.jare.2025.11.031
Abstract

Introduction: Cardiac adipose tissue, which directly interfaces with the myocardium and vasculature, has a pivotal role in obesity-related cardiovascular pathology through its metabolic activity. This tissue contributes to cardiac remodeling through its regulation of lipid metabolism. Among the key organelles involved, peroxisomes have a central role in lipid metabolism, yet their contribution to obesity-induced cardiac dysfunction remains poorly understood.

Objectives: This study investigated whether peroxisomal dysfunction in cardiac adipose tissue drives obesity-associated cardiac hypertrophy.

Methods: Using a high-fat diet (HFD)-induced obese rat model, we evaluated changes in cardiac adipose tissues, focusing on their browning capacity and metabolic functions. To investigate mechanistic effects, H9C2 cardiomyocytes were exposed either to fatty acids extracted from cardiac adipose tissues or conditioned medium derived from adipocytes treated with mitochondrial and peroxisomal inhibitors (Mdivi-1 or 10,12-tricosadiynoic acid).

Results: HFD-fed obese rats exhibited significant expansion of cardiac adipose tissues and cardiac hypertrophy, driven by impaired lipid metabolism and loss of browning capacity in cardiac fat associated with peroxisomal dysfunction. Treatment of H9C2 cardiomyocytes with conditioned medium from adipocytes with peroxisomal dysfunction induced Collagen accumulation, increased expression of pro-inflammatory cytokines, and cellular hypertrophy, which recapitulates key pathological features observed in vivo.

Conclusion: Our findings demonstrate that peroxisomal dysfunction in cardiac adipose tissue drives lipid metabolic reprogramming and contributes to obesity-related cardiac hypertrophy. Targeting peroxisomal function in cardiac fat could be a novel therapeutic approach to mitigate obesity-induced cardiovascular remodeling.

Keywords

Cardiac adipose tissue; Cardiac hypertrophy; Obesity; Peroxisome.

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