Liraglutide impacts iron homeostasis in a murine model of hereditary hemochromatosis.

Classic hereditary hemochromatosis (HH) is an autosomal recessive iron-overload disorder resulting from loss-of-function mutations of the HFE gene. HH patients exhibit excessive hepatic iron accumulation that predisposes these patients to liver disease, including the risk for developing liver cancer. Chronic iron overload also poses a risk for the development of metabolic disorders such as obesity, type 2 diabetes and insulin resistance. We hypothesized that liraglutide, GLP1 Receptor agonist (GLP1RA), alters iron metabolism while also reducing body weight and glucose tolerance in a mouse model of HH (global HFE knockout, HFE KO) and diet-induced obesity and glucose intolerance. The total body HFE KO and WT control mice were fed high-fat diet for 8 weeks. Mice were subdivided into liraglutide and vehicle-treated groups and received daily subcutaneous administration of the respective treatment once daily for 18 weeks. Liraglutide improved glucose tolerance, hepatic lipid markers and reduced body weight in a mouse model of HH, the HFE KO mouse, similar to WT controls. Importantly, our data shows that liraglutide alters iron metabolism in HFE KO mice, leading to decreased circulating and stored iron levels in HFE KO mice. These observations highlight the potential that GLP1RA could be utilized to reduce iron overload in addition to reducing body weight and improving glucose regulation in HH patients.