RGD Reference Report - Delayed ethanol elimination and enhanced susceptibility to ethanol-induced hepatosteatosis after liver resection. - Rat Genome Database

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Delayed ethanol elimination and enhanced susceptibility to ethanol-induced hepatosteatosis after liver resection.

Authors: Liu, X  Hakucho, A  Liu, J  Fujimiya, T 
Citation: Liu X, etal., World J Gastroenterol. 2014 Dec 28;20(48):18249-59. doi: 10.3748/wjg.v20.i48.18249.
RGD ID: 11075083
Pubmed: PMID:25561792   (View Abstract at PubMed)
PMCID: PMC4277962   (View Article at PubMed Central)
DOI: DOI:10.3748/wjg.v20.i48.18249   (Journal Full-text)

AIM: To investigate ethanol-induced hepatic steatosis after liver resection and the mechanisms behind it. METHODS: First, the preliminary examination was performed on 6 sham-operated (Sham) and 30 partial hepatectomy (PH) male Wistar rats (8-wk-old) to evaluate the recovery of the liver weight and liver function after liver resection. PH rats were sacrificed at the indicated time points (4, 8, and 12 h; 1, 3, and 7 d) after PH. Second, the time point for the beginning of the chronic ethanol exposure (1 wk after sham- or PH-operation) was determined based on the results of the preliminary examination. Finally, pair-feeding was performed with a controlled diet or with a 5-g/dL ethanol liquid diet for 28 d in another 35 age-matched male Wistar rats with a one-week recovery after undergoing a sham- (n = 15) or PH-operation (n = 20) to evaluate the ethanol-induced liver injury after liver resection. Hepatic steatosis, liver function, fatty acid synthase (Fas) gene expression level, the expression of lipid metabolism-associated enzyme regulator genes [sterol regulatory element binding protein (Srebp)-1 and peroxisome proliferator-activated receptor (Ppar)-alpha], the mediators that alter lipid metabolism [plasminogen activator (Pai)-1 gene expression level and tumor necrosis factor (Tnf)-alpha production], and hepatic class-1 alcohol dehydrogenase (Adh1)-associated ethanol elimination were investigated in the 4 groups based on histological, immunohistochemical, biochemical, Western blotting, reverse transcriptase chain reaction, and blood ethanol concentration analyses. The relevant gene expression levels, liver weight, and liver function were assessed before and 1 wk after surgery to determine the subject's recovery from the liver resection using the rats that had been subjected to the preliminary examination. RESULTS: In the PH rats, ethanol induced marked hepatic steatosis with impaired liver functioning, as evidenced by the accumulation of fatty droplets within the hepatocytes, the higher increases in their hepatic triglyceride and blood alanine aminotransferase and blood aspartate aminotransferase levels after the 28-d pair-feeding period. The Sham-ethanol rats, not the PH-ethanol rats, demonstrated the up-regulation of Srebp-1 and the down-regulation of Ppar-alpha mRNA expression levels after the 28-d pair-feeding period. The 28-d ethanol administration induced the up-regulation of Pai-1 gene expression level and an overproduction of TNF-alpha in the Sham and the PH rats; however, the effect was more significant in the PH rats. The PH-ethanol rats (n = 4) showed higher residual blood ethanol concentrations than did the Sham-ethanol rats (n = 6) after a 5-h fast (0.66 +/- 0.4 mg/mL vs 0.2 +/- 0.1 mg/mL, P < 0.05); these effects manifested without up-regulation of Adh1 gene expression, which was present in the Sham-ethanol group after the 28-d pair-feeding period. One week after the liver resection, the liver weight, function, the gene expression levels of Fas, Srebp-1, Ppar-alpha, Pai-1 and Tnf-alpha recovered; however, the Adh1 gene expression did not recover in rats. CONCLUSION: Desensitization to post-hepatectomy ethanol treatment and slow recovery from PH in Adh1 gene expression enhanced the susceptibility to ethanol-induced hepatic steatosis after PH in rats.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alcoholic Fatty Liver  ISOSerpine1 (Rattus norvegicus)11075083; 11075083mRNA:increased expression:liver (rat)RGD 
Alcoholic Fatty Liver  IEP 11075083mRNA:increased expression:liver (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Serpine1  (serpin family E member 1)

Genes (Mus musculus)
Serpine1  (serine (or cysteine) peptidase inhibitor, clade E, member 1)

Genes (Homo sapiens)
SERPINE1  (serpin family E member 1)


Additional Information