Back to Search
Start Over
A Translational Mouse Model for NASH with Advanced Fibrosis and Atherosclerosis Expressing Key Pathways of Human Pathology
A Translational Mouse Model for NASH with Advanced Fibrosis and Atherosclerosis Expressing Key Pathways of Human Pathology
- Source :
- Cells, 9, 9, 2014, Cells, Volume 9, Issue 9, Cells, Vol 9, Iss 2014, p 2014 (2020)
- Publication Year :
- 2020
-
Abstract
- Non-alcoholic steatohepatitis (NASH) is a fast-growing liver disorder that is associated with an increased incidence of cardiovascular disease and type 2 diabetes. Animal models adequately mimicking this condition are scarce. We herein investigate whether Ldlr&minus<br />/&minus<br />Leiden mice on different high-fat diets represent a suitable NASH model. Ldlr&minus<br />Leiden mice were fed a healthy chow diet or fed a high-fat diet (HFD) containing lard or a fast food diet (FFD) containing milk fat. Additionally, the response to treatment with obeticholic acid (OCA) was evaluated. Both high-fat diets induced obesity, hyperlipidemia, hyperinsulinemia, and increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Mice on both diets developed progressive macro- and microvesicular steatosis, hepatic inflammation, and fibrosis, along with atherosclerosis. HFD induced more severe hyperinsulinemia, while FFD induced more severe hepatic inflammation with advanced (F3) bridging fibrosis, as well as more severe atherosclerosis. OCA treatment significantly reduced hepatic inflammation and fibrosis, and it did not affect atherosclerosis. Hepatic transcriptome analysis was compared with human NASH and illustrated similarity. The present study defines a translational model of NASH with progressive liver fibrosis and simultaneous atherosclerosis development. By adaptation of the fat content of the diet, either insulin resistance (HFD) or hepatic inflammation and fibrosis (FFD) can be aggravated.
- Subjects :
- Liver Cirrhosis
Male
0301 basic medicine
Inflammation
fibrosis
Biomedical Innovation
Liver disorder
Mice
chemistry.chemical_compound
0302 clinical medicine
Life
Non-alcoholic Fatty Liver Disease
Fibrosis
Hyperlipidemia
Hyperinsulinemia
Medicine
lcsh:QH301-705.5
Mice, Knockout
NASH
Obeticholic acid
food and beverages
General Medicine
Metabolic syndrome
Treatment Outcome
030211 gastroenterology & hepatology
MHR - Metabolic Health Research
Healthy Living
medicine.medical_specialty
Hyperlipidemias
Chenodeoxycholic Acid
Diet, High-Fat
Article
03 medical and health sciences
Insulin resistance
Hyperinsulinism
Internal medicine
NAFLD
Animals
Animal model
Obesity
business.industry
nutritional and metabolic diseases
medicine.disease
Atherosclerosis
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Endocrinology
lcsh:Biology (General)
Receptors, LDL
chemistry
inflammation
Fast Foods
ELSS - Earth, Life and Social Sciences
Steatohepatitis
Transcriptome
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cells, 9, 9, 2014, Cells, Volume 9, Issue 9, Cells, Vol 9, Iss 2014, p 2014 (2020)
- Accession number :
- edsair.doi.dedup.....a951c12414c252499d59ab033ca0be2b