title: FOXO transcription factors protect against the diet-induced fatty liver disease.
abstract: Forkhead O transcription factors (FOXOs) have been implicated in glucose and lipid homeostasis; however, the role of FOXOs in the development of nonalcoholic fatty liver disease (NAFLD) is not well understood. In this study, we designed experiments to examine the effects of two different diets-very high fat diet (HFD) and moderately high fat plus cholesterol diet (HFC)-on wildtype (WT) and liver-specific Foxo1/3/4 triple knockout mice (LTKO). Both diets induced severe hepatic steatosis in the LTKO mice as compared to WT controls. However, the HFC diet led to more severe liver injury and fibrosis compared to the HFD diet. At the molecular levels, hepatic Foxo1/3/4 deficiency triggered a significant increase in the expression of inflammatory and fibrotic genes including Emr1, Ccl2, Col1a1, Tgfb, Pdgfrb, and Timp1. Thus, our data suggest that FOXO transcription factors play a salutary role in the protection against the diet-induced fatty liver disease.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.|Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Hyeong-Geug
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.|Roudebush Veterans Administration Medical Center, Indianapolis, Indiana 46202, USA.
authors.forename: Suthat
authors.initials: S
authors.lastname: Liangpunsakul
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: X Charlie
authors.initials: XC
authors.lastname: Dong
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat; D005247:Feeding Behavior; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000097:blood / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000235:genetics / Q000473:pathology; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D009928:Organ Specificity; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D051858:Forkhead Transcription Factors; D014280:Triglycerides; D002784:Cholesterol; D000410:Alanine Transaminase