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

• DOI: 10.2337/db23-0814
• Publication Date: 2024-02-23T21:26:41Z
• Authors: Yao Zhang; Quanxin Jiang; Xingxing Liang; Qiqi Qian; Jie Xiong; Chuchu Liu; Junting Xu; Ning Wang; Ying Xu; Peihui Zhou; Sijia Lu; Qian Zhou; Yanmei Yuan; Xuemei Fan; Junli Liu; Suzhen Chen
• Keywords: Steatosis; CD36; Steatohepatitis

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