Regulation of Iron and Its Significance in Obesity and Complications

Chan, Yee Kwan; Sung, Hye Kyoung; Sweeney, Gary

Abstract

Iron is an essential micronutrient with important roles in many critical physiological processes, especially as a structural component of hemoglobin responsible for oxygen transport. Iron homeostasis is tightly regulated, yet perturbations resulting in iron deficiency as well as iron overload are linked with obesity and associated metabolic abnormalities, such as insulin resistance and type 2 diabetes. The endocrine system plays an active role in regulating iron homeostasis and here we have highlighted the importance of lipocalin-2 (Lcn2) and hepcidin. Circulating and adipose tissue expression of the proinflammatory Lcn2 are elevated in obesity and this may be an important, and underestimated, regulator of iron homeostasis. Hepcidin is also markedly elevated during obesity and by inducing the internalization of ferroportin, it leads to an accumulation of tissue iron stores but deficiency in circulating iron, a key feature of functional iron deficiency. Due to the critical importance of iron homeostasis in health and disease, there are currently several well established methods for clinical diagnosis of iron levels and various therapeutics have proven effective in restoring normal iron level in iron deficient or overload conditions. Further explorations in the endocrine regulation of iron homeostasis are warranted to develop a better understanding of the pathophysiological roles of iron in obesity and related metabolic diseases.