Regulating iron overload: Liraglutide’s potential advantages

Research reveals liraglutide’s potential to control iron metabolism and enhance glucose tolerance in a mouse mannequin of hereditary hemochromatosis and weight problems.

Research: Liraglutide Impacts Iron Homeostasis in a Murine Mannequin of Hereditary Hemochromatosis. Picture Credit score: Peter Togel / Shutterstock.com

A current Endocrinology examine assesses the function of liraglutide in regulating iron metabolism in a mouse mannequin of hereditary hemochromatosis, diet-induced weight problems, and glucose intolerance.

Remedy choices for hereditary hemochromatosis

Hepcidin, which is encoded by the Hamp gene, regulates the absorption of iron from the intestines, recycling by macrophages, and launch of saved iron from hepatocytes. The protein HFE regulates hepcidin manufacturing by way of its interactions with different proteins like transferrin receptor 1 (TfR1) and TfR2, which sense when iron ranges are excessive inside the blood. Loss-of-function mutations of the HFE gene result in an autosomal recessive iron-overload dysfunction known as hereditary hemochromatosis (HH).

Extreme hepatic iron accumulation is noticed in HH sufferers, which will increase their threat of growing liver illness and deadly organ harm, in addition to kind 2 diabetes (T2D), weight problems, and insulin resistance. Customary remedies for HH embody serial therapeutic phlebotomy, which lowers the shops of tissue and plasma iron.

Liraglutide, a glucagon-like peptide-1 agonist (GLP-1A), is used for the administration of T2D and weight problems, with current research suggesting its helpful results on obesity-related liver pathology, which may contain aberrations in iron metabolism. In a single beforehand phlebotomy-dependent HH affected person with T2D, using liraglutide helped keep regular ferritin ranges and lowered glycated hemoglobin ranges with out phlebotomy.

In regards to the examine

The present examine hypothesized that liraglutide may cut back physique weight, improve glucose tolerance, and alter iron metabolism in Hfe knockout (KO) mice. To this finish, wild-type (WT) and HFE KO mice have been fed a high-fat weight-reduction plan to induce weight problems, adopted by dosing with both saline or liraglutide for 18 weeks. At week 14, an intraperitoneal glucose tolerance check was performed.

At three time factors, mice underwent a physique composition evaluation to measure lean and fats mass. Full blood cell counts, whole iron-binding capability (TIBC), serum iron, and ferritin saturation ranges have been additionally measured.

Research findings

Liraglutide efficiently lowered fats mass, physique weight, and lean mass in each HFE KO and WT mice. Glucose tolerance in each teams was additionally improved with liraglutide administration, thus suggesting that the drug’s perform is just not instantly influenced by increased iron ranges. These observations additionally spotlight the profitable therapy potential of liraglutide for obesity-related metabolic illness.

As in comparison with WT mice, circulating iron ranges have been increased in HFE KO and saline-treated mice. Though liraglutide therapy didn’t restore serum iron ranges to regular ranges, it considerably lowered serum iron ranges in HFE KO mice.

Moreover, as in comparison with WT mice, HFE KO mice exhibited decrease TIBC, whereas each teams exhibited decrease TIBC following liraglutide therapy. HFE KO mice had increased ferritin saturation, which remained unchanged by liraglutide, thus demonstrating that liraglutide bettering iron overload.

Liraglutide therapy additionally lowered hematocrit, hemoglobin, and purple blood cell counts in each WT and HFE KO mice, though not under the decrease sure of the conventional vary in mice. Reticulocyte, platelet, and imply corpuscular hemoglobin (MCH) concentrations have been unaffected by genotype or drug therapy. Liraglutide barely raised lymphocytes and decreased monocytes in HFE KO mice.

The Hamp gene was not differentially expressed within the liver tissue after liraglutide therapy or between genotypes. These outcomes counsel a hepcidin-independent mechanism by way of which liraglutide therapy reduces hepatic iron ranges.

Liraglutide therapy lowered liver weight, regardless of the genotype, in addition to hepatic lipid ranges by lowering Scd1 transcription, which corresponds to the lower in whole liver iron shops. Throughout the 2 subgroups, fatty acid synthase (FASN) and peroxisome proliferator-activated receptor alpha (PPARα) weren’t differentially expressed, thereby indicating that liver weight and steatosis are successfully mitigated by liraglutide therapy in HFE KO and WT mice.

Conclusions

The examine findings exhibit that liraglutide therapy can modify iron metabolism in HFE KO mice whereas additionally assuaging obesity-related metabolic illness. HH results in extreme iron accumulation within the liver, which will increase the chance of growing liver most cancers and different metabolic syndromes; subsequently, GLP1As like liraglutide could also be an efficient therapy possibility for these sufferers.

GLP1As might be used to scale back iron overload along with decreasing physique weight and bettering glucose regulation in HH sufferers.”