RGD Reference Report - High-fat-cholesterol diet mainly induced necrosis in fibrotic steatohepatitis rat by suppressing caspase activity. - Rat Genome Database

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High-fat-cholesterol diet mainly induced necrosis in fibrotic steatohepatitis rat by suppressing caspase activity.

Authors: Yetti, Husna  Naito, Hisao  Jia, Xiaofang  Shindo, Moritaka  Taki, Hitoshi  Tamada, Hazuki  Kitamori, Kazuya  Hayashi, Yumi  Ikeda, Katsumi  Yamori, Yukio  Nakajima, Tamie 
Citation: Yetti H, etal., Life Sci. 2013 Nov 4;93(18-19):673-80. doi: 10.1016/j.lfs.2013.09.013. Epub 2013 Sep 23.
RGD ID: 27226810
Pubmed: PMID:24071521   (View Abstract at PubMed)
DOI: DOI:10.1016/j.lfs.2013.09.013   (Journal Full-text)


AIM: Apoptosis and necrosis occur in nonalcoholic steatohepatitis (NASH) and are thought to be related to fibrosis. A stroke-prone spontaneously hypertensive (SHRSP5/Dmcr) rat fed a high-fat-cholesterol (HFC) diet exhibited similar pathological features to human NASH with severe liver fibrosis. We aimed to reveal the molecular pathway and to confirm the relationship between cell death, fibrosis and K18Asp396 levels, a neoepitope generated during cleavage of keratin 18 by caspases, as a candidate for biomarker of hepatic damage in this animal model.
MAIN METHODS: Male rats were fed with control and HFC diets for 2, 8 and 14 weeks. Liver apoptosis cells, necrosis score, and the molecular mechanism and K18Asp396 levels were investigated.
KEY FINDINGS: HFC diet increased TUNEL-positive cells only at 2 weeks and necrosis scores strongly in the livers of rats during the entire period. This diet increased hepatic Bax/Bak but decreased Bcl-2/Bcl-xl expression during the entire period; however, it upregulated caspase 8, 9, and 3/7 activities only at 2 weeks, but downregulated them at 14 weeks. Additionally, this diet did not increase hepatic cytochrome c expression. Serum K18Asp396 levels have a positive correlation with necrosis score.
SIGNIFICANCE: In SHRSP5/Dmcr rats, HFC diet caused hepatocyte necrosis rather than apoptosis by the downregulation of all caspase activity. Serum K18Asp396 levels may be a good biomarker of hepatocyte necrosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
metabolic dysfunction-associated steatohepatitis severityISOKrt18 (Rattus norvegicus)27226810; 27226810protein:altered degradation:liver and serum (rat)RGD 
metabolic dysfunction-associated steatohepatitis severityIEP 27226810protein:altered degradation:liver and serum (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to nutrient levels  IEP 27226810high fat dietRGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
extracellular space  IDA 27226810MMO:0000712RGD 

Objects Annotated

Genes (Rattus norvegicus)
Krt18  (keratin 18)

Genes (Mus musculus)
Krt18  (keratin 18)

Genes (Homo sapiens)
KRT18  (keratin 18)


Additional Information