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Addition of trans fat and alcohol has divergent effects on atherogenic diet-induced liver injury in rodent models of steatohepatitis.
Am J Physiol Gastrointest Liver Physiol. 2020 03 01; 318(3):G410-G418.AJ

Abstract

Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are common causes of chronic liver disease. The overlap between ALD and NAFLD suggests the existence of metabolic steatohepatitis. Development of in vivo models that reflect various aspects of human steatohepatitis is essential for drug discovery. We aimed to characterize several models of steatohepatitis (SH) and to investigate whether the pathology could be modulated. Sprague-Dawley rats were fed a high-fat diet (HFD) for 9 wk, followed by either a high-fat, high-cholesterol and cholate diet (HFC) or a HFC diet containing 13% trans fat (HFC-TF). A subset received 15% ethanol-water twice a week for 12 wk. Serum triglycerides, cholesterol, LDL, HDL, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and rodent NH2-terminal propeptide of type III collagen (rPRO-C3) were assessed. The liver was weighed and evaluated using modified Nonalcoholic Steatohepatitis Clinical Research Network histological score system criteria. All diets induced hepatomegaly, but only HFC-TF increased the size of visceral adipose tissue. Trans fat augmented HFC-induced dyslipidemia, and cholesterol was higher and HDL was lower in the HFC-TF groups. Alcohol lowered triglycerides in both dietary groups. HFC elevated ALT and AST, which were lowered by trans fat. All diets induced histological SH, addition of trans fat induced more steatosis but less inflammation. Inclusion of alcohol augmented the HFC-induced inflammation. All diets induced mild fibrosis. Inclusion of trans fat and alcohol significantly increased rPRO-C3. The addition of trans fat reduced the HFC-induced inflammation but augmented steatosis and dyslipidemia. Inclusion of alcohol induced a more inflammatory and fibrogenic phenotype.NEW & NOTEWORTHY Alcoholic liver disease and nonalcoholic liver disease share significant overlap, which suggests the existence of metabolic steatohepatitis. Trans fat has been implicated in steatohepatitis development. Here, we show that the addition of trans fat to an atherogenic diet results in a more steatotic but less inflammatory phenotype, whereas the addition of alcohol to an atherogenic diet augments the inflammatory and fibrogenic properties of the diet.

Authors+Show Affiliations

Nordic Bioscience Biomarkers and Research, Herlev, Denmark. Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.Nordic Bioscience Biomarkers and Research, Herlev, Denmark.Department of Pathology, Odense University Hospital, Odense, Denmark.Department of Pathology, Odense University Hospital, Odense, Denmark.Nordic Bioscience Biomarkers and Research, Herlev, Denmark.Nordic Bioscience Biomarkers and Research, Herlev, Denmark.Innovative Medicines Unit, Grünenthal, Aachen, Germany.Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.Nordic Bioscience Biomarkers and Research, Herlev, Denmark.Nordic Bioscience Biomarkers and Research, Herlev, Denmark.Innovative Medicines Unit, Grünenthal, Aachen, Germany.Innovative Medicines Unit, Grünenthal, Aachen, Germany.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

31905026

Citation

Daniels, Samuel J., et al. "Addition of Trans Fat and Alcohol Has Divergent Effects On Atherogenic Diet-induced Liver Injury in Rodent Models of Steatohepatitis." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 318, no. 3, 2020, pp. G410-G418.
Daniels SJ, Leeming DJ, Detlefsen S, et al. Addition of trans fat and alcohol has divergent effects on atherogenic diet-induced liver injury in rodent models of steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2020;318(3):G410-G418.
Daniels, S. J., Leeming, D. J., Detlefsen, S., Bruun, M. F., Hjuler, S. T., Henriksen, K., Hein, P., Krag, A., Karsdal, M. A., Nielsen, M. J., Brockbank, S., & Cruwys, S. (2020). Addition of trans fat and alcohol has divergent effects on atherogenic diet-induced liver injury in rodent models of steatohepatitis. American Journal of Physiology. Gastrointestinal and Liver Physiology, 318(3), G410-G418. https://doi.org/10.1152/ajpgi.00066.2019
Daniels SJ, et al. Addition of Trans Fat and Alcohol Has Divergent Effects On Atherogenic Diet-induced Liver Injury in Rodent Models of Steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2020 03 1;318(3):G410-G418. PubMed PMID: 31905026.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Addition of trans fat and alcohol has divergent effects on atherogenic diet-induced liver injury in rodent models of steatohepatitis. AU - Daniels,Samuel J, AU - Leeming,Diana J, AU - Detlefsen,Sönke, AU - Bruun,Maria F, AU - Hjuler,Sara T, AU - Henriksen,Kim, AU - Hein,Peter, AU - Krag,Aleksander, AU - Karsdal,Morten A, AU - Nielsen,Mette Juul, AU - Brockbank,Sarah, AU - Cruwys,Simon, Y1 - 2020/01/06/ PY - 2020/1/7/pubmed PY - 2020/8/4/medline PY - 2020/1/7/entrez KW - alcoholic KW - metabolic KW - nonalcoholic KW - rodent models KW - steatohepatitis SP - G410 EP - G418 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am. J. Physiol. Gastrointest. Liver Physiol. VL - 318 IS - 3 N2 - Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are common causes of chronic liver disease. The overlap between ALD and NAFLD suggests the existence of metabolic steatohepatitis. Development of in vivo models that reflect various aspects of human steatohepatitis is essential for drug discovery. We aimed to characterize several models of steatohepatitis (SH) and to investigate whether the pathology could be modulated. Sprague-Dawley rats were fed a high-fat diet (HFD) for 9 wk, followed by either a high-fat, high-cholesterol and cholate diet (HFC) or a HFC diet containing 13% trans fat (HFC-TF). A subset received 15% ethanol-water twice a week for 12 wk. Serum triglycerides, cholesterol, LDL, HDL, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and rodent NH2-terminal propeptide of type III collagen (rPRO-C3) were assessed. The liver was weighed and evaluated using modified Nonalcoholic Steatohepatitis Clinical Research Network histological score system criteria. All diets induced hepatomegaly, but only HFC-TF increased the size of visceral adipose tissue. Trans fat augmented HFC-induced dyslipidemia, and cholesterol was higher and HDL was lower in the HFC-TF groups. Alcohol lowered triglycerides in both dietary groups. HFC elevated ALT and AST, which were lowered by trans fat. All diets induced histological SH, addition of trans fat induced more steatosis but less inflammation. Inclusion of alcohol augmented the HFC-induced inflammation. All diets induced mild fibrosis. Inclusion of trans fat and alcohol significantly increased rPRO-C3. The addition of trans fat reduced the HFC-induced inflammation but augmented steatosis and dyslipidemia. Inclusion of alcohol induced a more inflammatory and fibrogenic phenotype.NEW & NOTEWORTHY Alcoholic liver disease and nonalcoholic liver disease share significant overlap, which suggests the existence of metabolic steatohepatitis. Trans fat has been implicated in steatohepatitis development. Here, we show that the addition of trans fat to an atherogenic diet results in a more steatotic but less inflammatory phenotype, whereas the addition of alcohol to an atherogenic diet augments the inflammatory and fibrogenic properties of the diet. SN - 1522-1547 UR - https://www.unboundmedicine.com/medline/citation/31905026/Addition_of_trans_fat_and_alcohol_has_divergent_effects_on_atherogenic_diet_induced_liver_injury_in_rodent_models_of_steatohepatitis_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00066.2019?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -