Ferroptosis and metabolic syndrome and complications: association, mechanism, and translational applications

Abstract

Metabolic syndrome is a medical condition characterized by several metabolic disorders in the body. Long-term metabolic disorders raise the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Therefore, it is essential to actively explore the aetiology of metabolic syndrome (MetS) and its comorbidities to provide effective treatment options. Ferroptosis is a new form of cell death that is characterized by iron overload, lipid peroxide accumulation, and decreased glutathione peroxidase 4(GPX4) activity, and it involves the pathological processes of a variety of diseases. Lipid deposition caused by lipid diseases and iron overload is significant in metabolic syndrome, providing the theoretical conditions for developing ferroptosis. Recent studies have found that the major molecules of ferroptosis are linked to common metabolic syndrome consequences, such as T2DM and atherosclerosis. In this review, we first discussed the mechanics of ferroptosis, the regulatory function of inducers and inhibitors of ferroptosis, and the significance of iron loading in MetS. Next, we summarized the role of ferroptosis in the pathogenesis of MetS, such as obesity, type 2 diabetes, and atherosclerosis. Finally, we discussed relevant ferroptosis-targeted therapies and raised some crucial issues of concern to provide directions for future Mets-related treatments and research.

Hazel Leaf Polyphenol Extract Alleviated Cisplatin-Induced Acute Kidney Injury by Reducing Ferroptosis through Inhibiting Hippo Signaling

“…Recently, studies have revealed the harmful effects of iron, specifically ferroptosis, which can lead to renal tissue damage [27][28][29]. Hu et al conducted experiments using cisplatin-injected mice to create an AKI model and found that the ferroptosis inhibitor Fer-1 significantly reduced serum urea nitrogen and creatinine levels, thereby alleviating renal damage [10].…”

Red Oranges and Olive Leaf Waste-Derived Bioactive Extracts Promote Adipocyte Functionality In Vitro

“…Indeed, high iron levels may contribute to the continuous release of adipokines and promote an inflammatory environment, redirecting immune responses and promoting obesity occurrence [ 14 ]. Obesity-related persistent inflammation is characterized by the disproportionate release of FFAs and proinflammatory cytokines from adipocytes; this has led to the hypothesis of a connection between obesity and ferroptosis [ 15 ]. Ferroptosis, which was identified in 2012, is an iron-dependent cell death mechanism that is distinct from apoptosis, necrosis, and other cellular death mechanisms.…”