Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

International Journal of Molecular Sciences

Teresa Auguet¹  Alba Berlanga¹  Esther Guiu-Jurado¹  Salomé Martinez³  José Antonio Porras²  Gemma Aragonès¹  Fátima Sabench⁴  Mercé Hernandez⁴  Carmen Aguilar¹  Joan Josep Sirvent³  Daniel Del Castillo⁴  Cristl Richart¹ 

[1] 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; E-Mails:;Servei Medicina Interna, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, Tarragona 43007, Spain; E-Mail:;Servei Anatomia Patològica, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, Tarragona 43007, Spain; E-Mails:;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; E-Mails:

关键词: insulin resistance;    morbid obesity;    fatty acid metabolism;    non-alcoholic fatty liver disease;    simple steatosis;    non-alcoholic steatohepatitis;   

DOI  :  10.3390/ijms151222173

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.