PMID- 27439539 OWN - NLM STAT- MEDLINE DCOM- 20170609 LR - 20181113 IS - 1535-3699 (Electronic) IS - 1535-3702 (Print) IS - 1535-3699 (Linking) VI - 241 IP - 18 DP - 2016 Dec TI - Effects of iron supplementation in mice with hypoferremia induced by obesity. PG - 2049-2055 LID - 10.1177/1535370216660398 [doi] AB - Iron is an important micronutrient, but it can also act as a dangerous element by interfering with glucose homeostasis and inflammation, two features that are already disturbed in obese subjects. In this work, we study the effects of systemic iron supplementation on metabolic and inflammatory responses in mice with hypoferremia induced by obesity to better characterize whether iron worsens the parameters that are already altered after 24 weeks of a high-fat diet (HFD). Mice were maintained on a control diet or a HFD for 24 weeks and received iron-III polymaltose (50 mg/kg/every 2 days) during the last two weeks. Glucose homeostasis (basal glucose and insulin test tolerance) and systemic and visceral adipose tissue (VAT) inflammation were assessed. Iron levels were measured in serum. The Prussian blue reaction was used in isolated macrophages to detect iron deposition. Iron supplementation resulted in an increased number of VAT macrophages that were positive for Prussian blue staining as well as increased serum iron levels. Systemic hepcidin, leptin, resistin, and monocyte chemoattractant protein-1 (MCP-1) levels were not altered by iron supplementation. Local adipose tissue inflammation was also not made worse by iron supplementation because the levels of hepcidin, MCP-1, leptin, and interleukin (IL)-6 were not altered. In contrast, iron supplementation resulted in an increased production of IL-10 by adipose tissue and VAT macrophages. Leukocytosis and VAT plasminogen activator inhibitor-1 (PAI-1) level were reduced, but insulin resistance was not altered after iron supplementation. In conclusion, systemic iron supplementation in mice with hypoferremia induced by obesity did not worsen inflammatory marker or adipose tissue inflammation or the metabolic status established by obesity. Iron deposition was observed in adipose tissue, mainly in macrophages, suggesting that these cells have mechanisms that promote iron incorporation without increasing the production of inflammatory mediators. FAU - Gotardo, Erica Martins Ferreira AU - Gotardo EM AD - Clinical Pharmacology and Gastroenterology Unit, Sao Francisco University Medical School, Braganca Paulista 12916-900, SP, Brazil. FAU - Caria, Cintia Rabelo E Paiva AU - Caria CR AD - Clinical Pharmacology and Gastroenterology Unit, Sao Francisco University Medical School, Braganca Paulista 12916-900, SP, Brazil. FAU - de Oliveira, Caroline Candida AU - de Oliveira CC AD - Clinical Pharmacology and Gastroenterology Unit, Sao Francisco University Medical School, Braganca Paulista 12916-900, SP, Brazil. FAU - Rocha, Thalita AU - Rocha T AD - Clinical Pharmacology and Gastroenterology Unit, Sao Francisco University Medical School, Braganca Paulista 12916-900, SP, Brazil. FAU - Ribeiro, Marcelo Lima AU - Ribeiro ML AD - Clinical Pharmacology and Gastroenterology Unit, Sao Francisco University Medical School, Braganca Paulista 12916-900, SP, Brazil. FAU - Gambero, Alessandra AU - Gambero A AD - Clinical Pharmacology and Gastroenterology Unit, Sao Francisco University Medical School, Braganca Paulista 12916-900, SP, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160724 PL - Switzerland TA - Exp Biol Med (Maywood) JT - Experimental biology and medicine (Maywood, N.J.) JID - 100973463 RN - 0 (Blood Glucose) RN - 0 (Cytokines) RN - 0 (Ferric Compounds) RN - 0 (Hepcidins) RN - E1UOL152H7 (Iron) RN - UM5219H89V (teferrol) SB - IM MH - Anemia, Iron-Deficiency/drug therapy/*etiology MH - Animals MH - Blood Glucose/analysis MH - Cytokines/blood MH - Dietary Supplements MH - Ferric Compounds/*therapeutic use MH - Hepcidins/blood MH - Inflammation/drug therapy/etiology MH - Intra-Abdominal Fat/drug effects/metabolism MH - Iron/blood MH - Male MH - Mice MH - Obesity/*complications PMC - PMC5102132 OTO - NOTNLM OT - Hepcidin OT - adipokine OT - adipose tissue OT - adipose tissue macrophage EDAT- 2016/07/22 06:00 MHDA- 2017/06/10 06:00 PMCR- 2017/06/01 CRDT- 2016/07/22 06:00 PHST- 2016/07/22 06:00 [pubmed] PHST- 2017/06/10 06:00 [medline] PHST- 2016/07/22 06:00 [entrez] PHST- 2017/06/01 00:00 [pmc-release] AID - 1535370216660398 [pii] AID - 10.1177_1535370216660398 [pii] AID - 10.1177/1535370216660398 [doi] PST - ppublish SO - Exp Biol Med (Maywood). 2016 Dec;241(18):2049-2055. doi: 10.1177/1535370216660398. Epub 2016 Jul 24.