Differentially Expressed Genes in Response to a Squalene-Supplemented Diet Are Accurate Discriminants of Porcine Non-Alcoholic Steatohepatitis
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/16/12552 |
| Summary: | 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<sub>2</sub> 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 (<i>ENPEP</i>) was correlated with triglyceride content, while alpha-fetoprotein (<i>AFP</i>), neutralized E3 ubiquitin protein ligase 3 (<i>NEURL3</i>), 2′-5′-oligoadenylate synthase-like protein (<i>OASL</i>), and protein phosphatase 1 regulatory inhibitor subunit 1B (<i>PPP1R1B</i>) were correlated with activity reflecting inflammation and ballooning, and <i>NEURL3</i> with the SAF score. <i>AFP</i>, <i>ENPEP</i>, and <i>PPP1R1B</i> exhibited a remarkably strong discriminant power compared to those pathological parameters in both experimental groups. Moreover, the expression of <i>PPP1R1B</i>, <i>TMEM45B</i>, <i>AFP</i>, and <i>ENPEP</i> 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. |
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| ISSN: | 1661-6596 1422-0067 |