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Possible mechanisms on the aggravation from moderate alcohol consumption in nonalcoholic steatohepatitis in rats
Author(s) -
IP Blanche,
Nascimento Andre F.,
Luvizotto Renata A.M.,
Wang Yan,
Wang XiangDong
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb188
Subject(s) - adiponectin , endocrinology , medicine , nonalcoholic steatohepatitis , endoplasmic reticulum , chemistry , fatty liver , alcohol , steatosis , steatohepatitis , chop , downregulation and upregulation , insulin resistance , nonalcoholic fatty liver disease , gene , biochemistry , diabetes mellitus , disease
We have demonstrated that moderate alcohol consumption in rats with pre‐existing nonalcoholic steatohepatitis (NASH) exacerbates liver injury (Wang Y. et al., ACER 2010). The underlying mechanisms involving adiponectin‐hepatic adiponectin receptor (AdipoR) signaling pathway or the endoplasmic reticulum (ER) stress responses remain unclear. In the present study, Sprague‐Dawley rats were fed with a high‐fat diet (HFD 71% of total energy from fat) for 6 weeks to induce NASH, then divided into 2 sub‐groups (n=10): fed a HFD (55% fat) or a high‐fat alcoholic diet (HFA, 55% fat, 16% ethanol) for additional 4 weeks. In comparison to HFD group, we found 1) plasma adiponectin decreased in the HFA group, with the difference closed to reaching statistical significance (p=0.0596); 2) hepatic AdipoR1 but not AdipoR2, was significantly decreased in HFA; 3) the gene expression of FAS and the protein expression of SREBP‐1c were up‐regulated, while the gene expressions of DGAT1/2 and CPT‐I were down‐regulated in HFA group. Unexpectedly, HFA resulted in significant increase in pAMPK, pACC and SIRT‐1 protein levels. No changes were shown in ER stress mediated protein expression of CHOP, which induces apoptosis, between two groups. These data suggest that moderate alcohol consumption down‐regulates the adiponectin‐AdipoR1 and up‐regulates fatty acids biosynthesis, which promotes liver injury in rats with pre‐existing NASH.