Ethanol and High Cholesterol Diet Causes Severe Steatohepatitis and Early Liver Fibrosis in Mice
Publication Date
September 27, 2016
Journal
PLOS ONE
Authors
Yasodha Krishnasamy, Venkat K. Ramshesh, Monika Gooz, Rick G. Schnellmann, et al
Volume
11
Issue
9
Pages
e0163342
DOI
https://dx.plos.org/10.1371/journal.pone.0163342
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0163342
Scopus
84991632943
Mendeley
http://www.mendeley.com/research/ethanol-high-cholesterol-diet-causes-severe-steatohepatitis-early-liver-fibrosis-mice
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Mendeley | Further Information

{"title"=>"Ethanol and high cholesterol diet causes severe steatohepatitis and early liver fibrosis in mice", "type"=>"journal", "authors"=>[{"first_name"=>"Yasodha", "last_name"=>"Krishnasamy", "scopus_author_id"=>"51863980200"}, {"first_name"=>"Venkat K.", "last_name"=>"Ramshesh", "scopus_author_id"=>"6602338870"}, {"first_name"=>"Monika", "last_name"=>"Gooz", "scopus_author_id"=>"6602209813"}, {"first_name"=>"Rick G.", "last_name"=>"Schnellmann", "scopus_author_id"=>"7006257901"}, {"first_name"=>"John J.", "last_name"=>"Lemasters", "scopus_author_id"=>"17035432100"}, {"first_name"=>"Zhi", "last_name"=>"Zhong", "scopus_author_id"=>"16433232300"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"612795445", "pmid"=>"27676640", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0163342", "scopus"=>"2-s2.0-84991632943", "sgr"=>"84991632943"}, "id"=>"bc2af42f-811b-3fd5-a8e5-4c3eea472e81", "abstract"=>"BACKGROUND AND AIM: Because ethanol consumption is commonly associated with a high cholesterol diet, we examined whether combined consumption of ethanol and high cholesterol increases liver injury and fibrosis. METHODS: Male C57BL/6J mice were fed diets containing: 1) 35% of calories from corn oil (CTR), 2) CTR plus 0.5% (w/v) cholesterol (Chol), 3) CTR plus ethanol (27% of calories) (EtOH), or 4) EtOH+Chol for 3 months. RESULTS: In mice fed Chol or EtOH alone, ALT increased to ~160 U/L, moderate hepatic steatosis occurred, and leukocyte infiltration, necrosis, and apoptosis increased modestly, but no observable fibrosis developed. By contrast in mice fed EtOH+Chol, ALT increased to ~270 U/L, steatosis was more extensive and mostly macrovesicular, and expression of proinflammatory molecules (HMGB-1, TLR4, TNFalpha, ICAM-1) and leukocyte infiltration increased substantially. Necrosis and apoptosis also increased. Trichrome staining and second harmonic generation microscopy revealed hepatic fibrosis. Fibrosis was mostly sinusoidal and/or perivenular, but in some mice bridging fibrosis occurred. Expression of smooth muscle alpha-actin and TGF-beta1 increased slightly by Chol, moderately by EtOH, and markedly by EtOH+Chol. TGF-beta pseudoreceptor BAMBI increased slightly by Chol, remained unchanged by EtOH and decreased by EtOH+Chol. MicroRNA-33a, which enhances TGF-beta fibrotic effects, and phospho-Smad2/3, the down-stream signal of TGF-beta, also increased more greatly by EtOH+Chol than Chol or EtOH. Metalloproteinase-2 and -9 were decreased only by EtOH+Chol. CONCLUSION: High dietary cholesterol and chronic ethanol consumption synergistically increase liver injury, inflammation, and profibrotic responses and suppress antifibrotic responses, leading to severe steatohepatitis and early fibrosis in mice.", "link"=>"http://www.mendeley.com/research/ethanol-high-cholesterol-diet-causes-severe-steatohepatitis-early-liver-fibrosis-mice", "reader_count"=>10, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Doctoral Student"=>1, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Doctoral Student"=>1, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>4, "Immunology and Microbiology"=>1, "Medicine and Dentistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}}, "group_count"=>0}

Scopus | Further Information

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