Hepatic galectin-3 is associated with lipid droplet area in non-alcoholic steatohepatitis in a new swine model

Abstract

Non-alcoholic fatty liver disease (NAFLD) is currently a growing epidemic disease that can lead to cirrhosis and hepatic cancer when it evolves into non-alcoholic steatohepatitis (NASH), a gap not well understood. To characterize this disease, pigs, considered to be one of the most similar to human experimental animal models, were used. To date, all swine-based settings have been carried out using rare predisposed breeds or long-term experiments. Herein, we fully describe a new experimental swine model for initial and reversible NASH using cross-bred animals fed on a high saturated fat, fructose, cholesterol, cholate, choline and methionine-deficient diet. To gain insight into the hepatic transcriptome that undergoes steatosis and steatohepatitis, we used RNA sequencing. This process significantly up-regulated 976 and down-regulated 209 genes mainly involved in cellular processes. Gene expression changes of 22 selected transcripts were verified by RT-qPCR. Lipid droplet area was positively associated with CD68, GPNMB, LGALS3, SLC51B and SPP1, and negatively with SQLE expressions. When these genes were tested in a second experiment of NASH reversion, LGALS3, SLC51B and SPP1 significantly decreased their expression. However, only LGALS3 was associated with lipid droplet areas. Our results suggest a role for LGALS3 in the transition of NAFLD to NASH.

The constitutively active form of a key cholesterol synthesis enzyme is lipid droplet-localized and upregulated in endometrial cancer tissues

“…Indeed, sequestration of metabolites from their regulatory effectors contributes to the constitutive activation of lipid synthesis in cancer cells ( 26 ). Squalene accumulation also increases LD biogenesis, size, and clustering ( 64 , 76 , 77 ), hinting at a wider role in their dynamics that remains to be explored.…”

Key genes involved in nonalcoholic steatohepatitis improvement after bariatric surgery

“…However, in this experiment, there was no significant difference in SQLE expression in NASH mice ( Figure 8G ). Meanwhile, in a porcine NASH model, SQLE was negatively correlated with hepatic lipid droplet area ( 62 ). The reason for this may be due to insufficient modeling time and species differences.…”

SPP1 and CXCL9 Promote Non-alcoholic Steatohepatitis Progression Based on Bioinformatics Analysis and Experimental Studies

“…Previous studies have revealed that the expression of SPP1 is upregulated in NAFLD and NASH liver tissues. In a new swine model of NASH, SPP1 gene expression was significantly positively correlated with lipid droplet area and inflammation, and when NASH was reversed, SPP1 gene expression was significantly reduced ( 22 ). A cross-sectional survey of 19 NASH patients reported that plasma SPP1 levels in NASH patients were higher than those in HC patients, whereas plasma and hepatic SPP1 levels in patients with advanced fibrosis were higher than those in patients with no or mild fibrosis, indicating that the histological characteristics of disease severity in NASH patients are associated with SPP1 ( 23 ).…”