Introduction: The influences of dietary fatty acids on the progress of chronic liver diseases have attracted lots of attentions, but the mechanisms of the effects of lipids rich in saturated fatty acids or PUFAs on hepatic fibrogenesis remain unclear.
Methods: Female Fischer 344 rats were fed normal chow or chow plus 20% (w/w) of corn oil or lard, respectively, and injected CCl4 twice a week for 4 weeks to induce liver fibrosis. Masson's staining was adopted to illustrate the fibrosis level. The mRNA expression level of α-SMA and the DNA methylation level of its promoter region were analyzed. A 2-DE gel based proteomic approach was constructed to investigate the differential expression level of hepatic proteome between three diet groups.
Results: Histological evaluations and α-SMA expression analysis illustrated the high corn oil intake has no effects on hepatic fibrogenesis, but lard intake aggravated liver fibrosis, partly attributed to DNA demethylation of α-SMA promoter region. 2-DE Gel based proteomic study demonstrated excessive lard consumption elevated the expression of fibrosis related alpha-1-antitrypsin precursor, and endoplasmic reticulum stress related proteins such as heat shock cognate 71 kDa, eukaryotic translation initiation factor 4A1 and protein disulfide isomerase associated 3. Moreover, unlike corn oil rich in PUFAs, lard had no effects to elevate the expression of glutathione S-transferases, but decreased the expression of iron store related proteins heme binding protein 1 and ferritin.
Conclusions: Lard intake aggravates CCl4 induced liver fibrosis via enhancing the expression of fibrogenesis and ER stress related proteins, and disturbing the hepatic transmethylation reaction.
Keywords: Carbon tetrachloride; Corn oil; Lard; Liver fibrosis; Proteomics.
Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.