Iron-Mediated Regulation in Adipose Tissue: A Comprehensive Review of Metabolism and Physiological Effects

Review the latest data regarding the intersection of adipose tissue (AT) and iron to meet the needs of AT metabolism and the progression of related diseases.

Iron is involved in fundamental biological metabolic processes and is precisely fine-tuned within the body to maintain cellular, tissue and even systemic iron homeostasis. AT not only serves as an energy storage depot but also represents the largest endocrine organ in the human body, maintaining systemic metabolic homeostasis. It is involved in physiological processes such as energy storage, insulin sensitivity regulation and lipid metabolism. As a unique iron-sensing tissue, AT expresses related regulatory factors, including the classic hepcidin, ferroportin (FPN), iron regulatory protein/iron responsive element (IRP/IRE) and ferritin. Consequently, the interaction between AT and iron is intricately intertwined. Imbalance of iron homeostasis produces the potential risks of steatosis, impaired glucose tolerance and insulin resistance, leading to AT dysfunction diseases, including obesity, type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). Despite the role of AT iron has garnered increasing attention in recent years, a comprehensive review that systematically organizes the connection between iron and AT remains lacking. Given the necessity of iron homeostasis, emphasizing its potential impact on AT function and metabolism regulation provides valuable insights into physiological effects such as adipocyte differentiation and thermogenesis. Futhermore, regulators including adipokines, mitochondria and macrophages have been mentioned, along with analyzing the novel perspective of iron as a key mediator influencing the fat-gut crosstalk.