Evaluation of high‐fat high‐fructose diet treatment in factor <scp>VIII</scp> (coagulation factor)‐deficient mouse model

Mishra, Alaknanda; Arindkar, Shailendra; Sahay, Preeti; Kumar, Jerald Mahesh; Upadhyay, Pramod; Majumdar, Subeer S.; Nagarajan, Priyadharsini

doi:10.1111/iep.12264

Cited by 3 publications

(2 citation statements)

References 22 publications

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“…The FVIII-deficient mice fed a high-fat diet developed hepatic steatosis, fibrosis, impaired energy metabolism, decreased platelet count, up-regulated de novo fatty acid synthesis, and lipid accumulation. 122 FVIII deficiency also has been linked to liver regeneration after partial hepatectomy. Progressive loss of FVIII mRNA expression was shown to be associated with partial hepatectomy in mice.…”

Section: Use Of a Factor Viii-deficient Murine Model To Study Cldmentioning

confidence: 99%

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Exploring the Complex Role of Coagulation Factor VIII in Chronic Liver Disease

Pradhan‐Sundd

Gudapati²,

Kamiński³

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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Chronic liver disease is one of the leading causes of death in the United States. Coagulopathy is often a sequela of chronic liver disease, however, the role and regulation of coagulation components in chronic liver injury remain poorly understood. Clinical and experimental evidence indicate that misexpression of the procoagulant factor VIII (FVIII) is associated with chronic liver disease. Nevertheless, the molecular mechanism of FVIII-induced chronic liver injury progression remains unknown. This review provides evidence supporting a pathologic role for FVIII in the development of chronic liver disease using both experimental and clinical models.

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Section: Use Of a Factor Viii-deficient Murine Model To Study Cldmentioning

confidence: 99%

Section: Use Of a Factor Viii–deficient Murine Model To Study Cldmentioning

confidence: 99%

Exploring the Complex Role of Coagulation Factor VIII in Chronic Liver Disease

Pradhan‐Sundd

Gudapati²,

Kamiński³

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

View full text Add to dashboard Cite

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Liver-related aspects of valoctocogene roxaparvovec gene therapy for hemophilia A: expert guidance for clinical practice

La Mura,

Cardinale,

De Cristofaro

et al. 2024

Blood Advances

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Adeno-associated virus–based gene therapy (valoctocogene roxaparvovec) is an attractive treatment for hemophilia A. Careful clinical management is required to minimize the risk of hepatotoxicity, including assessment of baseline liver condition to determine treatment eligibility and monitoring liver function after gene therapy. This article describes recommendations (developed by a group of hemophilia experts) on hepatic function monitoring before and after gene therapy. To prevent harmful liver-related effects, gene therapy is contraindicated in patients with uncontrolled liver infections, autoimmune hepatitis, liver stiffness ≥8 kPa, or cirrhosis. Before using gene therapy in patients with liver steatosis or other liver disorders, the risk of liver damage should be considered using a highly individualized approach. Treatment is not recommended in patients with abnormal liver enzymes, including alanine aminotransferase (ALT) at any level above the upper limit of normal (ULN). Therefore, pretreatment assessment of liver health should include laboratory tests, abdominal ultrasound, and liver stiffness measurements by transient elastography (TE). In the first year after therapy, ALT levels should be monitored 1 to 2 times per week to detect elevations ≥1.5× ULN, which may require immunosuppressant therapy. Patients with ALT elevation should receive prednisone 60 mg/d for 2 weeks, followed by stepwise tapering when ALT returns to baseline. ALT monitoring should continue long term (every 3-6 months), along with abdominal ultrasound (every 6 months) and TE (yearly) evaluations. When patients with good liver health are selected for treatment and closely monitored thereafter, ALT elevations can be promptly treated and are expected to resolve without long-term hepatic sequelae.

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Coagulation Factor VII Fine-tunes Hepatic Steatosis by Blocking AKT-CD36–Mediated Fatty Acid Uptake

Zhang,

Jiang,

Liang

et al. 2024

Diabetes

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NAFLD is considered as a risk factor for cardiovascular and cerebrovascular disease owing to its close association with coagulant disturbances. However, the precise biological functions and mechanisms that connect coagulation factors to NAFLD pathology remain inadequately understood. Herein, with unbiased bioinformatic analyses followed by functional test, we demonstrate that hepatic expression of coagulation factor FVII decreases in patients and mice with NAFLD/NASH. By employing adenovirus-mediated F7-knockdown and hepatocyte-specific F7-knockout mouse models, our mechanistic investigations unveil a non-coagulant function of hepatic FVII in mitigating lipid accumulation and lipotoxicity. This protective effect is achieved through the suppression of fatty acid (FA) uptake, orchestrated via the AKT-CD36 pathway. Interestingly, we observed that intracellular FVII directly interacts with AKT and PP2A, thereby promoting their association and triggering the dephosphorylation of AKT. Therapeutic intervention through adenovirus-mediated liver-specific overexpression of FVII has resulted in noteworthy improvements in liver steatosis, inflammation, injury and fibrosis in severely afflicted NAFLD mice. In conclusion, our findings highlight coagulation factor FVII as a critical regulator of hepatic steatosis and a potential target for the treatment of NAFLD and NASH.

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Evaluation of high‐fat high‐fructose diet treatment in factor VIII (coagulation factor)‐deficient mouse model

Cited by 3 publications

References 22 publications

Exploring the Complex Role of Coagulation Factor VIII in Chronic Liver Disease

Exploring the Complex Role of Coagulation Factor VIII in Chronic Liver Disease

Liver-related aspects of valoctocogene roxaparvovec gene therapy for hemophilia A: expert guidance for clinical practice

Coagulation Factor VII Fine-tunes Hepatic Steatosis by Blocking AKT-CD36–Mediated Fatty Acid Uptake

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