Molecular drivers of non-alcoholic steatohepatitis are sustained in mild-to-late fibrosis progression in a guinea pig model

Dietary Intervention Accelerates NASH Resolution Depending on Inflammatory Status with Minor Additive Effects on Hepatic Injury by Vitamin E Supplementation

“…The current interventions improved histopathological features and expression of target genes that correlated with reduced HC and HT in subgroups of both Chow and CvitE groups, indicating increased excretion and clearance of cholesterol and triglycerides in these animals. This is supported by the correlation with increased CYP7A1 expression in Chow subgroups, which indicates that the conversion of cholesterol to bile acids is increased [37]. Min et al showed CYP7A1 to be downregulated in liver samples of NASH patients compared to healthy controls and reported alterations in cholesterol and bile acid homeostatic pathways to be linked to disease severity [52].…”

“…Liver samples designated for q PCR analyses were flash frozen in liquid nitrogen and stored at −80 °C until use. Execution of RNA extraction, reverse transcription and q PCR analyses were performed as previously described [ 37 ]. Briefly, 1000 µL MagMax Lysis/Binding Solution Concentrate (Thermo Fisher, Waltham, MA, USA) and 0.7% β-mercaptoethanol (Sigma Aldrich, St. Louis, MO, USA) were used to homogenize 50 mg liver tissue.…”

“…To synthesize cDNA, 500 ng RNA was subjected to reverse transcription (High Capacity cDNA Reverse Transcription Kit; Thermo Fisher, Waltham, MA, USA) on a 2720 Thermal Cycler (Applied Biosystems, Foster City, CA, USA) at 25 • C for 10 min, 37 • C for 120 min, 85 • C 5 s. Prior to further analyses cDNA was controlled for genomic DNA contamination using an intron-spanning primer set (β-actin) [44]. Hypoxanthine phosphoribosyltransferase was used as reference gene [20,37]. Primer details are listed in Table 2.…”

“…Applying the validated guinea pig NASH model, the beneficial role of a diet change from a NASH-inducing high fat/high cholesterol diet to a low fat/no cholesterol diet, with and without a high-dose (2000 IU/d) vitE supplementation in a progressive disease state is evaluated. Endpoints include effects on histopathological hallmarks of NASH and biochemical markers of dyslipidemia and vitE status, and molecular markers of target genes associated with inflammation, fibrosis and hepatic lipid metabolism [37,38].…”

In‐depth mapping of the proteome of Tibetan pig tenderloin ( longissimus dorsi ) using offline high‐pH reversed‐phase fractionation and LC‐MS/MS

“…The enrichment of these disease‐related pathways in the proteome of Tibetan pig tenderloin was likely associated with the long feeding time (12–18 months) of Tibetan pigs. In addition, the “non‐alcoholic fatty liver disease” pathway was also significantly enriched, and this enrichment might be closely related to feeding intensity (Ipsen et al, ; Ye, Cheah, & Halliwell, ). In this study, the feeding mode of Tibetan pigs was semi‐stocking and half‐feeding, and the energy intake level was higher than the stocking mode.…”