Iron Homeostasis and Energy Metabolism in Obesity.

Abstract

Iron plays a role in energy metabolism as a component of vital enzymes and electron transport chains (ETCs) for adenosine triphosphate (ATP) synthesis. The tricarboxylic acid (TCA) cycle and oxidative phosphorylation are crucial in generating ATP in mitochondria. At the mitochondria matrix, heme and iron-sulfur clusters are synthesized. Iron-sulfur cluster is a part of the aconitase in the TCA cycle and a functional or structural component of electron transfer proteins. Heme is the prosthetic group for cytochrome c, a principal component of the respiratory ETC. Regarding fat metabolism, iron regulates mitochondrial fat oxidation and affects the thermogenesis of brown adipose tissue (BAT). Thermogenesis is a process that increases energy expenditure, and BAT is a tissue that generates heat via mitochondrial fuel oxidation. Iron deficiency may impair mitochondrial fuel oxidation by inhibiting iron-containing molecules, leading to decreased energy expenditure. Although it is expected that impaired mitochondrial fuel oxidation may be restored by iron supplementation, its underlying mechanisms have not been clearly identified. Therefore, this review summarizes the current evidence on how iron regulates energy metabolism considering the TCA cycle, oxidative phosphorylation, and thermogenesis. Additionally, we relate iron-mediated metabolic regulation to obesity and obesity-related complications.