title: Altered fatty acid metabolism-related gene expression in liver from morbidly obese women with non-alcoholic fatty liver disease.
abstract: Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in morbidly obese (MO) women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS), FA uptake and transport (PPARγ, CD36, FABP4), FA oxidation (PPARα), and inflammation (IL6, TNFα, CRP, PPARδ) were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13), simple steatosis (SS, n = 47) and non-alcoholic steatohepatitis (NASH, n = 67). Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively). Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively). Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis.
authors.affiliation: Grup de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili IISPV (IISPV), Tarragona 43003, Spain. aporras.hj23.ics@gencat.cat.
authors.forename: Teresa
authors.initials: T
authors.lastname: Auguet
authors.affiliation: Grup de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili IISPV (IISPV), Tarragona 43003, Spain. alba.berlanga@urv.cat.
authors.forename: Alba
authors.initials: A
authors.lastname: Berlanga
authors.affiliation: Grup de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili IISPV (IISPV), Tarragona 43003, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Guiu-Jurado
authors.affiliation: Servei Anatomia Patològica, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, Tarragona 43007, Spain. mgonzalez.hj23.ics@gencat.cat.
authors.forename: Salomé
authors.initials: S
authors.lastname: Martinez
authors.affiliation: Servei Medicina Interna, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, Tarragona 43007, Spain. aporras.hj23.ics@gencat.cat.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Porras
authors.affiliation: Grup de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili IISPV (IISPV), Tarragona 43003, Spain. gemma.aragones@iispv.cat.
authors.forename: Gemma
authors.initials: G
authors.lastname: Aragonès
authors.affiliation: Servei de Cirurgia, Hospital Sant Joan de Reus, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), IISPV, Avinguda Doctor Josep Laporte, 2, Tarragona 43204, Spain. fatima.sabench@urv.cat.
authors.forename: Fátima
authors.initials: F
authors.lastname: Sabench
authors.affiliation: Servei de Cirurgia, Hospital Sant Joan de Reus, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), IISPV, Avinguda Doctor Josep Laporte, 2, Tarragona 43204, Spain. mhernandezg@grupsagessa.com.
authors.forename: Mercé
authors.initials: M
authors.lastname: Hernandez
authors.affiliation: Grup de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili IISPV (IISPV), Tarragona 43003, Spain. caguilar.hj23.ics@gencat.cat.
authors.forename: Carmen
authors.initials: C
authors.lastname: Aguilar
authors.affiliation: Servei Anatomia Patològica, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, Tarragona 43007, Spain. jsirvent.hj23.ics@gencat.cat.
authors.forename: Joan Josep
authors.initials: JJ
authors.lastname: Sirvent
authors.affiliation: Servei de Cirurgia, Hospital Sant Joan de Reus, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), IISPV, Avinguda Doctor Josep Laporte, 2, Tarragona 43204, Spain. ddelcastillo@grupsagessa.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Del Castillo
authors.affiliation: Grup de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili IISPV (IISPV), Tarragona 43003, Spain. crichart.hj23.ics@gencat.cat.
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Richart
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009767:Obesity, Morbid / Q000150:complications* / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D014157:Transcription Factors; D005947:Glucose