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Deferoxamine ameliorates hepatosteatosis via several mechanisms in ob/ob mice
Author(s) -
Xue Han,
Chen Di,
Zhong YanKe,
Zhou ZhenDiao,
Fang ShiXin,
Li MingYao,
Guo Chuang
Publication year - 2016
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.13174
Subject(s) - steatosis , nonalcoholic fatty liver disease , deferoxamine , proinflammatory cytokine , medicine , endocrinology , insulin resistance , fatty liver , chemistry , diabetes mellitus , inflammation , disease
Hepatic iron accumulation may be responsible for the pathology of nonalcoholic fatty liver disease (NAFLD), which is both increasingly prevalent in conjunction with obesity and associated with comorbidities. The efficacy of iron reduction therapies, such as phlebotomy or dietary iron restriction, has been demonstrated in patient and animal models, including models of diabetes and obesity; however, the effects on and exact mechanisms responsible for iron depletion in NAFLD have not been clearly elucidated. Our study investigated the role of iron depletion by deferoxamine (DFO) treatment of ob/ob mice with hepatic steatosis. We found that DFO reduced hepatic iron deposition and regulated intracellular iron concentration in a homeostatic process following 15 days of treatment. Compared with vehicle treatment, DFO significantly improved hepatic steatosis by upregulating proteins related to lipid metabolism. Meanwhile, the reduction of free radical formation and proinflammatory cytokines, as well as the increase of hypoxia‐inducible factor‐1α pathway proteins and Bcl2/Bax ratio, further indicated that DFO was effective for liver protection and hepatic adaptation. These findings show that the intraperitoneal delivery of DFO provides a potential means of both preventing the progression of NAFLD and accelerating healing of hepatic steatosis, with the potential for rapid clinical application.