PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

Abstract

Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3) in the pathology of non-alcoholic fatty liver disease (NAFLD). Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR) analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18), simple steatosis (SS, n = 20), and non-alcoholic steatohepatitis (NASH, n = 17). Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis.

Network analyses identify liver‐specific targets for treating liver diseases

“…Circulating PCSK9 has also been found to be significantly associated with hepatic expression of SREBP‐1c and FASN, whereas PCSK9 mRNA levels have been found to be significantly correlated with steatosis severity and hepatic APOB, SREBP‐1c, and FASN expression (Ruscica et al , ). Aragones et al () have evaluated the association between liver PNPLA3 expression, key genes in lipid metabolism, and the presence of NAFLD in morbidly obese women and have reported that PNPLA3 expression was related to HS in these subjects. Their analysis indicates that PNPLA3 may be related to lipid accumulation in the liver, mainly in the development and progression of simple steatosis.…”

Weight loss induced by bariatric surgery restores adipose tissue PNPLA3 expression

“…Despite the emergence of PNPLA3 associated genetic risk for hepatic diseases, only few studies have investigated the pathophysiological regulation of PNPLA3. In a recent study by Aragones et al 32 increased PNPLA3 expression was associated with NAFLD. In contrast with this study, we did not observe a correlation between liver injury or weight loss on However, I148M-associated NAFLD is not associated with insulin resistance or adipose tissue inflammation.…”

“…Despite the emergence of PNPLA3 associated genetic risk for hepatic diseases, only few studies have investigated the pathophysiological regulation of PNPLA3 . In a recent study by Aragones et al . increased PNPLA3 expression was associated with NAFLD.…”

Analysis of polymorphic options of the eNOS, PNPLA3, CD14 genes at alcoholic liver disease

“…It has been shown that steatoshepatosis and hepatic fibrosis never develop in PNPLA3 knockout mice, and in conditions of gene hyperexpression, the synthesis of triglycerides and their accumulation in the carriers of the G-allele increases in connection with the genetically determined lower hydrolytic activity of the adiponutrin enzyme (17). The presence or appearance of obesity also affects the growth of the accumulation of triglycerides in carriers of the G-allele (18). Some authors point out that liver damage at non-alcoholic fatty dystrophy and ALD is diverse in nature, they differ in the phenotype of the disease and, accordingly, varying degrees of its progression (19).…”