Regulating iron overload: Liraglutide’s potential benefits

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.

Therapy 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 means 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 danger of growing liver illness and deadly organ injury, in addition to kind 2 diabetes (T2D), weight problems, and insulin resistance. Commonplace 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 useful results on obesity-related liver pathology, which might 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.

Concerning the examine

The present examine hypothesized that liraglutide might scale 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 had 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 take a look at was carried out.

At three time factors, mice underwent a physique composition evaluation to measure lean and fats mass. Full blood cell counts, complete iron-binding capability (TIBC), serum iron, and ferritin saturation ranges had 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 operate shouldn’t be straight influenced by greater iron ranges. These observations additionally spotlight the profitable remedy potential of liraglutide for obesity-related metabolic illness.

As in comparison with WT mice, circulating iron ranges had been greater in HFE KO and saline-treated mice. Though liraglutide remedy 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 remedy. HFE KO mice had greater ferritin saturation, which remained unchanged by liraglutide, thus demonstrating that liraglutide enhancing iron overload.

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

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

Liraglutide remedy lowered liver weight, no matter the genotype, in addition to hepatic lipid ranges by reducing Scd1 transcription, which corresponds to the lower in complete 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 remedy in HFE KO and WT mice.

Conclusions

The examine findings exhibit that liraglutide remedy 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 danger of growing liver most cancers and different metabolic syndromes; due to this fact, GLP1As like liraglutide could also be an efficient remedy choice for these sufferers.

GLP1As may very well be used to scale back iron overload along with lowering physique weight and enhancing glucose regulation in HH sufferers.”