Ferroptosis as a potential therapeutic target for obesity-related metabolic diseases

Chaodong Huang^1,2*Tao Luo³HUA ZHANG⁴Linhui Cheng⁵Shuhong Peng⁶Xiaowei Zhou⁷Lan Cao²Fangyou Chen²Junwei He²Chen Chen⁸Changhua Zhang^2,5*Yuai Zhang^9*Lingyun Zhong^2*

• ¹Jiangxi University of Traditional Chinese Medicine, Nanchang, China
• ²School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, China
• ³The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
• ⁴Department of Radiology, Nanchang First Hospital, Nanchang，Jiangxi Province, China
• ⁵Nanchang Research Institute, Sun Yat-sen University, Nanchang, Jiangxi Province, China
• ⁶Research Center for Differentiation and Development of Traditional Chinese Medicine Basic Theory, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, China
• ⁷Changzhou West Taihu Science and Technology Industrial Park Management committee, Changzhou, China
• ⁸Greater Brisbane Clinical School, Medical School, Faculty of Medicine, The University of Queensland, Herston, Queensland, Australia
• ⁹School of Pharmacy, Fudan University, Shanghai, Shanghai Municipality, China

Obesity represents one of the major public health issues threatening the global health and promoting chronic metabolic disorders, including type 2 diabetes, insulin resistance (IR), hyperlipidemia, hypertension, polycystic ovary syndrome, metabolicassociated fatty liver disease (MAFLD), and others. Ferroptosis, a novel form of cell death, is a programmed cell death induced by iron-dependent lipid peroxidation. It is characterized by excessive iron accumulation and unregulated lipid peroxidation. The activity of ferroptosis is modulated by multiple factors such as iron, reactive oxygen species, and over 98 unsaturated fatty acids. Mounting evidence indicates that ferroptosis plays a crucial role in obesity-related chronic metabolic diseases like type 2 diabetes, IR, hyperlipidemia, hypertension, polycystic ovary syndrome, and MAFLD. Clarifying the molecular mechanism of ferroptosis may discover potential therapeutic targets for the treatment of these diseases. This article comprehensively reviews the role, pathogenesis, prevention, treatment strategies, current research gaps and future development directions of ferroptosis in obesity-related chronic metabolic diseases have been thoroughly discussed, and novel perspectives for the future treatment and research of ferroptosis in these diseases carefully provided. It points out directions for basic research on ferroptosis, raises urgent needs for developing precise intervention strategies, and provides new insights into the treatment and study of obesity-related chronic metabolic diseases in the future.