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PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease.
Int J Mol Sci 2016; 17(5)IJ

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.

Authors+Show Affiliations

Group de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Institut Investigació Sanitària Pere Virgili (IISPV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), 43007 Tarragona, Spain. gemma.aragones@iispv.cat.Group de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Institut Investigació Sanitària Pere Virgili (IISPV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), 43007 Tarragona, Spain. tauguet.hj23.ics@gencat.cat. Servei Medicina Interna, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, 43007 Tarragona, Spain. tauguet.hj23.ics@gencat.cat.Group de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Institut Investigació Sanitària Pere Virgili (IISPV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), 43007 Tarragona, Spain. sandra.armengol@urv.cat.Group de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Institut Investigació Sanitària Pere Virgili (IISPV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), 43007 Tarragona, Spain. alba.berlanga@urv.cat.Group de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Institut Investigació Sanitària Pere Virgili (IISPV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), 43007 Tarragona, Spain. esther.guiu@urv.cat.Group de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Institut Investigació Sanitària Pere Virgili (IISPV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), 43007 Tarragona, Spain. caguilar.hj23.ics@gencat.cat.Servei Anatomia Patològica, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, 43007 Tarragona, Spain. mgonzalez.hj23.ics@gencat.cat.Servei de Cirurgia, Hospital Sant Joan de Reus, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), IISPV, Avinguda Doctor Josep Laporte, 2, 43204 Tarragona, Spain. fatima.sabench@urv.cat.Servei Medicina Interna, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, 43007 Tarragona, Spain. aporras.hj23.ics@gencat.cat.Servei Medicina Interna, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, 43007 Tarragona, Spain. drgorrin@yahoo.es.Servei de Cirurgia, Hospital Sant Joan de Reus, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), IISPV, Avinguda Doctor Josep Laporte, 2, 43204 Tarragona, Spain. mhernandezg@grupsagessa.com.Servei Anatomia Patològica, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, 43007 Tarragona, Spain. jsirvent.hj23.ics@gencat.cat.Servei de Cirurgia, Hospital Sant Joan de Reus, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), IISPV, Avinguda Doctor Josep Laporte, 2, 43204 Tarragona, Spain. ddelcastillo@grupsagessa.com.Group de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Institut Investigació Sanitària Pere Virgili (IISPV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), 43007 Tarragona, Spain. crichart.hj23.ics@gencat.cat. Servei Medicina Interna, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, 43007 Tarragona, Spain. crichart.hj23.ics@gencat.cat.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27128907

Citation

Aragonès, Gemma, et al. "PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women With Non-Alcoholic Fatty Liver Disease." International Journal of Molecular Sciences, vol. 17, no. 5, 2016.
Aragonès G, Auguet T, Armengol S, et al. PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease. Int J Mol Sci. 2016;17(5).
Aragonès, G., Auguet, T., Armengol, S., Berlanga, A., Guiu-Jurado, E., Aguilar, C., ... Richart, C. (2016). PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease. International Journal of Molecular Sciences, 17(5), doi:10.3390/ijms17050630.
Aragonès G, et al. PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women With Non-Alcoholic Fatty Liver Disease. Int J Mol Sci. 2016 Apr 27;17(5) PubMed PMID: 27128907.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease. AU - Aragonès,Gemma, AU - Auguet,Teresa, AU - Armengol,Sandra, AU - Berlanga,Alba, AU - Guiu-Jurado,Esther, AU - Aguilar,Carmen, AU - Martínez,Salomé, AU - Sabench,Fátima, AU - Porras,José Antonio, AU - Ruiz,Maikel Daniel, AU - Hernández,Mercé, AU - Sirvent,Joan Josep, AU - Del Castillo,Daniel, AU - Richart,Cristóbal, Y1 - 2016/04/27/ PY - 2016/02/24/received PY - 2016/04/19/revised PY - 2016/04/22/accepted PY - 2016/4/30/entrez PY - 2016/4/30/pubmed PY - 2017/2/23/medline KW - PNPLA3 KW - fatty acid metabolism KW - morbid obesity KW - non-alcoholic fatty liver disease KW - non-alcoholic steatohepatitis KW - simple steatosis JF - International journal of molecular sciences JO - Int J Mol Sci VL - 17 IS - 5 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/27128907/PNPLA3_Expression_Is_Related_to_Liver_Steatosis_in_Morbidly_Obese_Women_with_Non_Alcoholic_Fatty_Liver_Disease_ L2 - http://www.mdpi.com/resolver?pii=ijms17050630 DB - PRIME DP - Unbound Medicine ER -