Differentially Expressed Genes in Response to a Squalene-Supplemented Diet Are Accurate Discriminants of Porcine Non-Alcoholic Steatohepatitis.
Roubi AbuobeidLuis Vicente Herrera-MarcosCarmen ArnalSeyed Hesamoddin BidookiJavier Sánchez-MarcoRoberto LasherasJoaquín C SurraMaria Jesús Rodriguez-YoldiRoberto Martínez-BeamonteJesus OsadaPublished in: International journal of molecular sciences (2023)
Squalene is the major unsaponifiable component of virgin olive oil, the fat source of the Mediterranean diet. To evaluate its effect on the hepatic transcriptome, RNA sequencing was carried out in two groups of male Large White x Landrace pigs developing nonalcoholic steatohepatitis by feeding them a high fat/cholesterol/fructose and methionine and choline-deficient steatotic diet or the same diet with 0.5% squalene. Hepatic lipids, squalene content, steatosis, activity (ballooning + inflammation), and SAF (steatosis + activity + fibrosis) scores were analyzed. Pigs receiving the latter diet showed hepatic squalene accumulation and twelve significantly differentially expressed hepatic genes (log 2 fold change < 1.5 or <1.5) correlating in a gene network. These pigs also had lower hepatic triglycerides and lipid droplet areas and higher cellular ballooning. Glutamyl aminopeptidase ( ENPEP ) was correlated with triglyceride content, while alpha-fetoprotein ( AFP ), neutralized E3 ubiquitin protein ligase 3 ( NEURL3 ), 2'-5'-oligoadenylate synthase-like protein ( OASL ), and protein phosphatase 1 regulatory inhibitor subunit 1B ( PPP1R1B ) were correlated with activity reflecting inflammation and ballooning, and NEURL3 with the SAF score. AFP , ENPEP , and PPP1R1B exhibited a remarkably strong discriminant power compared to those pathological parameters in both experimental groups. Moreover, the expression of PPP1R1B , TMEM45B , AFP , and ENPEP followed the same pattern in vitro using human hepatoma (HEPG2) and mouse liver 12 (AML12) cell lines incubated with squalene, indicating a direct effect of squalene on these expressions. These findings suggest that squalene accumulated in the liver is able to modulate gene expression changes that may influence the progression of non-alcoholic steatohepatitis.
Keyphrases
- gene expression
- physical activity
- genome wide
- weight loss
- single cell
- fatty acid
- insulin resistance
- endothelial cells
- high fat diet
- dna methylation
- poor prognosis
- adipose tissue
- binding protein
- high resolution
- rna seq
- transcription factor
- metabolic syndrome
- mass spectrometry
- high throughput
- liver fibrosis
- skeletal muscle
- high fat diet induced