Details

Autor(en) / Beteiligte

• Crawford, Darrell H.G.
• Ross, Diana G.F.
• Jaskowski, Lesley-Anne
• Burke, Leslie J.
• Britton, Laurence J.
• Musgrave, Nick
• Briskey, David
• Rishi, Gautam
• Bridle, Kim R.
• Subramaniam, V. Nathan

Titel

Iron depletion attenuates steatosis in a mouse model of non-alcoholic fatty liver disease: Role of iron-dependent pathways

Ist Teil von

• Biochimica et biophysica acta. Molecular basis of disease, 2021-07, Vol.1867 (7), p.166142-166142, Article 166142

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2021

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Iron has been proposed as influencing the progression of liver disease in subjects with non-alcoholic fatty liver disease (NAFLD). We have previously shown that, in the Hfe−/− mouse model of hemochromatosis, feeding of a high-calorie diet (HCD) leads to increased liver injury. In this study we investigated whether the feeding of an iron deficient/HCD to Hfe−/− mice influenced the development of NAFLD. Liver histology was assessed in Hfe−/− mice fed a standard iron-containing or iron-deficient diet plus or minus a HCD. Hepatic iron concentration, serum transferrin saturation and free fatty acid were measured. Expression of genes implicated in iron regulation and fatty liver disease was determined by quantitative real-time PCR (qRT-PCR). Standard iron/HCD-fed mice developed severe steatosis whereas NAS score was reduced in mice fed iron-deficient HCD. Mice fed iron-deficient HCD had lower liver weights, lower transferrin saturation and decreased ferroportin and hepcidin gene expression than HCD-fed mice. Serum non-esterified fatty acids were increased in iron-deficient HCD-fed mice compared with standard iron HCD. Expression analysis indicated that genes involved in fatty-acid binding and mTOR pathways were regulated by iron depletion. Our results indicate that decreasing iron intake attenuates the development of steatosis resulting from a high calorie diet. These results also suggest that human studies of agents that modify iron balance in patients with NAFLD should be revisited. •Iron overload, HFE mutations and fatty liver disease co-exist in pathology.•Our data shows iron rather than the HFE mutation plays the critical pathogenic role•Independent effects of iron and a high-calorie diet on genes and pathways in disease