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However, the precise biological functions and mechanisms that connect coagulation factors to NAFLD pathology remain inadequately understood. Herein, with unbiased bioinformatics analyses followed by functional testing, we demonstrate that hepatic expression of coagulation factor VII (FVII) decreases in patients and mice with NAFLD\/nonalcoholic steatohepatitis (NASH). By using adenovirus-mediated F7-knockdown and hepatocyte-specific F7-knockout mouse models, our mechanistic investigations unveil a noncoagulant function of hepatic FVII in mitigating lipid accumulation and lipotoxicity. This protective effect is achieved through the suppression of fatty acid uptake, orchestrated via the AKT-CD36 pathway. Interestingly, 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 F7 results 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Article Highlights<\/jats:title>\n               <\/jats:sec>","DOI":"10.2337\/db23-0814","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T21:26:41Z","timestamp":1708723601000},"page":"682-700","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":7,"title":["Coagulation Factor VII Fine-tunes Hepatic Steatosis by Blocking AKT-CD36\u2013Mediated Fatty Acid Uptake"],"prefix":"10.2337","volume":"73","author":[{"given":"Yao","family":"Zhang","sequence":"first","affiliation":[{"name":"1Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quanxin","family":"Jiang","sequence":"additional","affiliation":[{"name":"1Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingxing","family":"Liang","sequence":"additional","affiliation":[{"name":"2Lingang Laboratory, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiqi","family":"Qian","sequence":"additional","affiliation":[{"name":"1Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Xiong","sequence":"additional","affiliation":[{"name":"1Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuchu","family":"Liu","sequence":"additional","affiliation":[{"name":"1Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junting","family":"Xu","sequence":"additional","affiliation":[{"name":"1Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"1Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[{"name":"1Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peihui","family":"Zhou","sequence":"additional","affiliation":[{"name":"1Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sijia","family":"Lu","sequence":"additional","affiliation":[{"name":"1Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Zhou","sequence":"additional","affiliation":[{"name":"1Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanmei","family":"Yuan","sequence":"additional","affiliation":[{"name":"1Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Fan","sequence":"additional","affiliation":[{"name":"3Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junli","family":"Liu","sequence":"additional","affiliation":[{"name":"1Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8616-2152","authenticated-orcid":false,"given":"Suzhen","family":"Chen","sequence":"additional","affiliation":[{"name":"1Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People\u2019s 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