Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 66, Issue 44, Pages 11612-11621Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.8b02974
Keywords
high-fat diet; hepatic iron content; TFR2; ZIP14; rat
Funding
- National Key Research and Development Program of China [2016YFD0500500]
- National Natural Science Foundation of China [31302053]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control
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High-fat diet-induced obesity is known to disturb hepatic iron metabolism in a time-dependent manner. The mechanism of decreased hepatic iron deposits induced by long-term high-fat diet needs to be further investigated. In this study, 24 6-week-old male Sprague-Dawley rats were given a 16-week high-fat diet and hepatic iron metabolism was examined. High-fat diet feeding considerably decreased hepatic iron contents, enhanced transferrin expression, and reduced the expression of ferritin heavy chain, ferritin light chain, and hepatic iron uptake-related proteins (transferrin receptor 2, TFR2, and ZRT/IRT-like protein 14, ZIP14) in rats. Impaired expression of hepatic TFR2 coincided with DNA hypermethylation on the promoter and repressed expression of transcription factor hepatocyte nuclear factor 4 alpha (HNF4 alpha). miR-181 family expression was markedly increased and verified to regulate Zip14 expression by the dual-luciferase reporter system. Taken together, long-term high-fat diet decreases hepatic iron storage, which is closely linked to inhibition of liver iron transport through the TFR2 and ZIP14-dependent pathway.
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