Melatonin attenuates high-fat diet- and particulate matter-induced cardiac injury: involvement of mitochondrial quality and miR-221/222 expression

Ya-Chun Chen ¹, Ming-Hsueh Lee ², Szu-Ju Fu ¹

¹Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
²Division of Neurosurgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan; Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan.
³Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi City, Chiayi County, Taiwan; Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi City, Chiayi County, Taiwan; Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Guishan District, Taoyuan City, Taiwan.
⁴Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Life Sciences, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan; The iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
⁵Department of Bioscience Technology, College of Science, Chung Yuan Christian University, Taoyuan, Taiwan; Center for Nanotechnology, Chung Yuan Christian University, Taoyuan, Taiwan.
⁶Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁷Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁸Department of Pulmonary Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan.
⁹Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan; Center for Complementary and Integrated Medicine, National Taiwan University Hospital, Taipei, Taiwan.

⁰Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Biochemical Pharmacology +

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September 19, 2025

View abstract on PubMed

Summary

Combined exposure to high-fat diets and particulate matter worsens heart cell damage. The antioxidant melatonin protects against this injury by improving mitochondrial function and involving miR-221/222.

Area Of Science

Cardiovascular Research
Toxicology
Mitochondrial Biology

Background

Cardiovascular disease (CVD) is influenced by hyperlipidemia and particulate matter (PM) individually.
The combined impact of high-fat diet (HFD)/palmitate (PA) and PM on cardiac health is not well understood.

Purpose Of The Study

To investigate if combined HFD/PA and PM exposure exacerbates cardiomyocyte injury.
To explore the protective role of melatonin against this combined insult.
To elucidate the involvement of mitochondria and miR-221/222 in melatonin's cardioprotective effects.

Main Methods

In vitro: H9c2 cells treated with PA, PM, and melatonin.
In vivo: Wild-type, miR-221/222 knockout, and overexpression mice subjected to HFD and PM exposure, with melatonin administration.
Assessment of cardiomyocyte apoptosis, fibrosis, mitochondrial function, and ROS levels.

Main Results

Combined PA/HFD and PM induced mitochondrial ROS accumulation, fission, excessive mitophagy, cardiomyocyte apoptosis, and fibrosis.
Melatonin treatment mitigated these detrimental effects, reducing ROS and improving cardiac function.
miR-221/222 upregulation was identified as a downstream mechanism of melatonin's protective action.

Conclusions

Simultaneous exposure to HFD/PA and PM significantly worsens cardiomyocyte injury and cardiac dysfunction.
Melatonin offers cardioprotection by scavenging ROS, preserving mitochondrial integrity, and modulating miR-221/222.
This study reveals a novel regulatory pathway involving miR-221/222 in mitigating combined HFD/PM-induced cardiac damage.

Keywords:

High-fat diet Melatonin Mitochondria Particulate matter ROS miR-221/222