Obesity Promotes Alterations in Iron Recycling

Abstract

Hepcidin is a key hormone that induces the degradation of ferroportin (FPN), a protein that exports iron from reticuloendothelial macrophages and enterocytes. The aim of the present study was to experimentally evaluate if the obesity induced by a high-fat diet (HFD) modifies the expression of FPN in macrophages and enterocytes, thus altering the iron bioavailability. In order to directly examine changes associated with iron metabolism in vivo, C57BL/6J mice were fed either a control or a HFD. Serum leptin levels were evaluated. The hepcidin, divalent metal transporter-1 (DMT1), FPN and ferritin genes were analyzed by real-time polymerase chain reaction. The amount of iron present in both the liver and spleen was determined by flame atomic absorption spectrometry. Ferroportin localization within reticuloendothelial macrophages was observed by immunofluorescence microscopy. Obese animals were found to exhibit increased hepcidin gene expression, while iron accumulated in the spleen and liver. They also exhibited changes in the sublocation of splenic cellular FPN and a reduction in the FPN expression in the liver and the spleen, while no changes were observed in enterocytes. Possible explanations for the increased hepcidin expression observed in HFD animals may include: increased leptin levels, the liver iron accumulation or endoplasmic reticulum (ER) stress. Together, the results indicated that obesity promotes changes in iron bioavailability, since it altered the iron recycling function.

Increased adiposity by feeding growing rats a high-fat diet results in iron decompartmentalisation

“…5(f)) in HF animals, suggesting a possible higher dietary Fe accessibility associated with this feeding condition. In rodent models, the effects of an HF diet on Fe status seem to be fundamentally influenced by the (1) rodent model, (2) experiment duration and (3) type and amount of fat used in diets (34,35,42,(46)(47)(48)(49)(50)(51)(52)(53)(54)(55) . Thus, some diet-induced obese rodents show a greater responsiveness to dietary fat overload, with a consequent increase in their body weight and fatness (12,13) .…”

“…From this perspective, the degree of inflammation produced by excess body fat may, to some extent, impact the production of hepcidin (5,6,43,58) , decrease intestinal Fe absorption and favour Fe accumulation in its major storage sites (liver and spleen). In most of the studies using C57BL/6 mice that aimed to evaluate the impact of HF diets on Fe status, the experimental duration ranged from 16 to 30 weeks (35,42,(46)(47)(48)(49) . In these studies, however, excessive fat intake resulted in decreased Fe concentration and hepcidin mRNA expression in the liver.…”

“…Conversely, studies using rats (mostly Sprague-Dawley rats) ranged from 5 to 12 weeks (49)(50)(51)(52) . Only one study with rats lasted for more than 12 weeks (16 weeks) (53) .…”

Iron Overload Effect on Serum Levels of Glucose, Insulin and HOMA-IR was Ifluenced by the Type of Fat in Female Sprague-Dawley Rats Fed High-Fat-Diets

“…Diet was provided in glass cups and water in glass drinking bottles. Rats were kept under controlled temperature (22 ± 2ºC) and maintained at a 12:12 hours light: dark cycles with free access to water and standard laboratory chow diet for one week of acclimatization [24]. This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.…”

“…Blood samples were collected by cardiac puncture and centrifuged immediately. Serum samples were as kept at -20ºC until used [24].…”