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Evaluation of high‐fat high‐fructose diet treatment in factor VIII (coagulation factor)‐deficient mouse model
Author(s) -
Mishra Alaknanda,
Arindkar Shailendra,
Sahay Preeti,
Kumar Jerald Mahesh,
Upadhyay Pramod K.,
Majumdar Subeer S.,
Nagarajan Perumal
Publication year - 2018
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12264
Subject(s) - steatosis , fatty liver , medicine , endocrinology , factor vii , pathogenesis , fructose , lipid metabolism , clotting factor , biology , coagulation , immunology , disease , biochemistry
Summary Non‐alcoholic fatty liver disease ( NAFLD )‐like conditions enhance the production and action of clotting factors in humans. However, studies examining the effect of NAFLD due to high‐fat high‐fructose (HFHF) diet in factor VIII ‐deficient (haemophilia A) animals or patients have not been reported previously. In this study, we investigated the individual role of factor VIII in the progression of diet‐induced NAFLD in the factor 8 −/− (F8 −/− ) mouse model system and its consequences on the haemophilic status of the mice. The F8 −/− mice were fed with HFHF diet for 14 weeks. Physiological, biochemical, haematological, molecular, pathological, and immune histochemical analyses were performed to evaluate the effect of this diet. The F8 −/− mice developed hepatic steatosis after 14 weeks HFHF diet and displayed lower energy metabolism, higher myeloid cell infiltration in the liver, decreased platelet count, upregulated de novo fatty acid synthesis, lipid accumulation, and collagen deposition. This study helps to understand the role of factor VIII in NAFLD pathogenesis and to analyse the severity and consequences of steatosis in haemophilic patients as compared to normal population. This study suggests that haemophilic animals (F8 −/− mice) are highly prone to hepatic steatosis and thrombocytopenia.