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HO‐1 Involvement In Iron Homeostasis In Liver Of Obese Mice
Author(s) -
Favero Gaia,
Sodhi Komal,
Puri Nitin,
Kim DongHyun,
Vanella Luca,
Rezzani Rita,
Rodella Luigi F.,
Abraham Nader G.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.661.7
Subject(s) - iron homeostasis , homeostasis , endocrinology , medicine , metabolism
In the United States, obesity is a major health problem that negatively impacts life quality and expectancy. In obesity increased levels of reactive oxygen species, increased levels of inflammatory cytokines, and altered iron homeostasis occur, however the mechanisms involved are unresolved. Heme oxygenase (HO‐1) confers cytoprotection against oxidative stress and, through its activity, liberates iron from heme, upregulating ferritin, responsible for sequestering free iron. We examined the effect of the HO‐1 inducer, cobalt protoporphyrin (CoPP), on the regulation of iron homeostasis in liver of obese mice. In obese mice HO‐1 expression was lower ( p < 0.05) and cytokine levels higher ( p < 0.05) compared to age matched lean mice. HO‐1 induction lowered body weight, serum levels of TNF‐α and IL‐6 ( p < 0.05) and cellular levels of iron. In particular, CoPP increased ferritin levels and icreased levels of ferroportin and decreased IREB1 and hepcidin ( p < 0.05). Conversely, inhibition of HO activity reversed all of these beneficial effects. The decrease in oxidative stress, via HO‐1 induction and increased HO‐1 activity, was associated with decreased cellular iron overload. These findings point to an effective strategy in the treatment of the metabolic consequences of obesity through alteration of liver iron homeostasis.