Addition of trans-fat and alcohol has divergent effects on atherogenic diet-induced liver injury in rodent models of steatohepatitis

Samuel Joseph Daniels, Diana Julie Leeming, Sönke Detlefsen, Maria Fuglsang Bruun, Sara Toftegaard Hjuler, Kim Henriksen, Peter Hein, Aleksander Krag, Morten Asser Karsdal, Mette Juul Nielsen, Sarah Brockbank, Simon Cruwys

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background Non-alcoholic 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. Methods Sprague Dawley rats were fed a high-fat diet (HFD) for 9 weeks, 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 weeks. Serum triglycerides, cholesterol, LDL, HDL, AST, ALT and rPRO-C3. The liver was weighed and evaluated using modified NASH-CRN criteria. Results All diets induced hepatomegaly but only HFC-TF increased the size of visceral adipose tissue. Trans-fat augmented HFC-induced dyslipidemia, 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 was lowered by trans-fat. All diets induced histological SH, addition of trans-fat induced a more steatotic 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. Conclusion 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.

OriginalsprogEngelsk
TidsskriftAmerican journal of physiology. Gastrointestinal and liver physiology
ISSN0193-1857
DOI
StatusE-pub ahead of print - 6. jan. 2020

Fingeraftryk

Atherogenic Diet
Fatty Liver
Rodentia
Fats
Alcohols
Liver
Wounds and Injuries
Diet
Dyslipidemias
Essential Drugs
Hepatomegaly
Intra-Abdominal Fat
High Fat Diet
LDL Cholesterol
HDL Cholesterol
Sprague Dawley Rats
Liver Diseases
Ethanol
Pathology

Citer dette

@article{987cd0a85bd54b7d8347cbab2a58651d,
title = "Addition of trans-fat and alcohol has divergent effects on atherogenic diet-induced liver injury in rodent models of steatohepatitis",
abstract = "Background Non-alcoholic 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. Methods Sprague Dawley rats were fed a high-fat diet (HFD) for 9 weeks, 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 weeks. Serum triglycerides, cholesterol, LDL, HDL, AST, ALT and rPRO-C3. The liver was weighed and evaluated using modified NASH-CRN criteria. Results All diets induced hepatomegaly but only HFC-TF increased the size of visceral adipose tissue. Trans-fat augmented HFC-induced dyslipidemia, 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 was lowered by trans-fat. All diets induced histological SH, addition of trans-fat induced a more steatotic 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. Conclusion 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.",
author = "Daniels, {Samuel Joseph} and Leeming, {Diana Julie} and S{\"o}nke Detlefsen and Bruun, {Maria Fuglsang} and Hjuler, {Sara Toftegaard} and Kim Henriksen and Peter Hein and Aleksander Krag and Karsdal, {Morten Asser} and Nielsen, {Mette Juul} and Sarah Brockbank and Simon Cruwys",
year = "2020",
month = "1",
day = "6",
doi = "10.1152/ajpgi.00066.2019",
language = "English",
journal = "American Journal of Physiology: Gastrointestinal and Liver Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",

}

Addition of trans-fat and alcohol has divergent effects on atherogenic diet-induced liver injury in rodent models of steatohepatitis. / Daniels, Samuel Joseph; Leeming, Diana Julie; Detlefsen, Sönke; Bruun, Maria Fuglsang; Hjuler, Sara Toftegaard; Henriksen, Kim; Hein, Peter; Krag, Aleksander; Karsdal, Morten Asser; Nielsen, Mette Juul; Brockbank, Sarah; Cruwys, Simon.

I: American journal of physiology. Gastrointestinal and liver physiology, 06.01.2020.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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 Joseph

AU - Leeming, Diana Julie

AU - Detlefsen, Sönke

AU - Bruun, Maria Fuglsang

AU - Hjuler, Sara Toftegaard

AU - Henriksen, Kim

AU - Hein, Peter

AU - Krag, Aleksander

AU - Karsdal, Morten Asser

AU - Nielsen, Mette Juul

AU - Brockbank, Sarah

AU - Cruwys, Simon

PY - 2020/1/6

Y1 - 2020/1/6

N2 - Background Non-alcoholic 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. Methods Sprague Dawley rats were fed a high-fat diet (HFD) for 9 weeks, 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 weeks. Serum triglycerides, cholesterol, LDL, HDL, AST, ALT and rPRO-C3. The liver was weighed and evaluated using modified NASH-CRN criteria. Results All diets induced hepatomegaly but only HFC-TF increased the size of visceral adipose tissue. Trans-fat augmented HFC-induced dyslipidemia, 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 was lowered by trans-fat. All diets induced histological SH, addition of trans-fat induced a more steatotic 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. Conclusion 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.

AB - Background Non-alcoholic 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. Methods Sprague Dawley rats were fed a high-fat diet (HFD) for 9 weeks, 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 weeks. Serum triglycerides, cholesterol, LDL, HDL, AST, ALT and rPRO-C3. The liver was weighed and evaluated using modified NASH-CRN criteria. Results All diets induced hepatomegaly but only HFC-TF increased the size of visceral adipose tissue. Trans-fat augmented HFC-induced dyslipidemia, 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 was lowered by trans-fat. All diets induced histological SH, addition of trans-fat induced a more steatotic 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. Conclusion 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.

U2 - 10.1152/ajpgi.00066.2019

DO - 10.1152/ajpgi.00066.2019

M3 - Journal article

C2 - 31905026

JO - American Journal of Physiology: Gastrointestinal and Liver Physiology

JF - American Journal of Physiology: Gastrointestinal and Liver Physiology

SN - 0193-1857

ER -