2. Academic Validation
  3. Berberine partially ameliorates cardiolipotoxicity in diabetic cardiomyopathy by modulating SIRT3-mediated lipophagy to remodel lipid droplets homeostasis

Berberine partially ameliorates cardiolipotoxicity in diabetic cardiomyopathy by modulating SIRT3-mediated lipophagy to remodel lipid droplets homeostasis

  • Br J Pharmacol. 2025 Apr 13. doi: 10.1111/bph.70035.
Wenxian Chen 1 2,  Tongzhu Jin 3 4,  Yilin Xie 5,  Changsheng Zhong 2,  Huiying Gao 4,  Lei Zhang 2,  Jin Ju 2,  Ting Cheng 2,  Mengyang Li 2,  Huifang Wang 2,  Zhenbo Yang 4,  Qin Deng 5,  Zhimin Du 1 6,  Haihai Liang 1 4 7
Affiliations

Affiliations

  • 1 Zhuhai People's Hospital, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Clinical Medical College of Jinan University, Zhuhai, China.
  • 2 School of Pharmacy, Health Science Center, Shenzhen University, Shen Zhen, China.
  • 3 Department of Pharmacy at the Second Affiliated Hospital, Harbin Medical University, Harbin, China.
  • 4 State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State Key Labratoray -Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China.
  • 5 School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen, China.
  • 6 State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China.
  • 7 Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2019RU070), Chinese Academy of Medical Sciences, Harbin, China.
PMID: 40222752 DOI: 10.1111/bph.70035
Abstract

Background and purpose: Emerging evidence indicated that the excessive lipid droplets (LDs) accumulation and lipotoxicity play a significant role in the development of diabetic cardiomyopathy (DCM), yet the regulatory mechanisms governing the function of cardiac LDs are still unknown. Lipophagy has been shown to be involved in the maintenance of LDs homeostasis. The objective of this study was to explore the mechanism of lipophagy in cardiomyocytes and investigate whether berberine could mitigate DCM by modulating this pathway.

Experimental approach: Bioinformatics analysis identified disorders of lipid metabolism and Autophagy in DCM. To carry out further research, db/db mice were utilized. Furthermore, H9C2 cells treated with palmitic acid were employed as a model to explore the molecular mechanisms involved in myocardial lipotoxicity.

Key results: The results showed that lipophagy was impaired in DCM. Mechanistically, Sirtuin 3 (SIRT3) was demonstrated to regulate lipophagy in cardiomyocytes. SIRT3 was down-regulated in DCM. Conversely, activation of SIRT3 by the activator nicotinamide riboside (NR) could promote lipophagy to alleviate PA-induced lipotoxicity in H9C2 cells. Moreover, berberine administration markedly mitigated diabetes-induced cardiac dysfunction and hypertrophy in db/db mice, which dependent on SIRT3-mediated lipophagy.

Conclusion and implications: Collectively, SIRT3 could moderate cardiac lipotoxicity in DCM by promoting lipophagy, suggesting that the regulation of SIRT3-mediated lipophagy may be a promising strategy for treating DCM. The findings indicate that the therapeutic potential of berberine for DCM is associated with lipophagy.

Keywords

SIRT3; berberine; diabetic cardiomyopathy; lipid droplets; lipophagy; mitochondria.

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