Altered fatty acid metabolism-related gene expression in liver from morbidly obese women with non-alcoholic fatty liver disease.
Altered fatty acid metabolism-related gene expression in liver from morbidly obese women with non-alcoholic fatty liver disease.
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DOI：
10.3390/ijms151222173
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发表时间：
2014-12-02
影响因子：
5.6
通讯作者：
Richart C
中科院分区：
文献类型：
--
作者：
Auguet T;Berlanga A;Guiu-Jurado E;Martinez S;Porras JA;Aragonès G;Sabench F;Hernandez M;Aguilar C;Sirvent JJ;Del Castillo D;Richart C
人类肝脏中的脂质积累似乎是非酒精性脂肪性肝病（NAFLD）发病机制和进展的关键机制。我们的目的是评估不同的脂肪酸（FA）代谢相关基因的基因表达在病态肥胖（MO）妇女与NAFLD。FA从头合成相关关键基因在肝脏中的表达（LXRα、SREBP 1c、ACC 1、FAS）、FA摄取和转运（PPARγ、CD 36、FABP 4）、FA氧化（PPARα）和炎症采用RT-qPCR方法检测127例肝组织学正常的MO患者血清IL 6、TNFα、CRP、PPARδ水平（NL，n = 13）、单纯性脂肪变性（SS，n = 47）和非酒精性脂肪性肝炎（NASH，n = 67）。与NL相比，患有SS和NASH的MO NAFLD女性的肝脏FAS mRNA表达显著更高（分别为p = 0.003，p = 0.010）。NASH受试者的肝脏IL 6和TNFα mRNA表达高于SS受试者（分别为p = 0.033，p = 0.050）。有趣的是，LXRα、ACC 1和FAS表达与脂肪变性程度呈负相关。这些结果通过蛋白质印迹分析证实。总之，我们的研究结果表明，脂肪生成似乎在SS的晚期下调，这表明，在这种类型的极端肥胖，脂肪生成途径的失调可能与脂肪变性的严重程度。
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.
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影响因子：
64.8
作者：
Mitro, Nico;Mak, Puiying A.;Saez, Enrique
通讯作者：
Saez, Enrique
肿瘤坏死因子-α的脂肪表达--在与肥胖相关的胰岛素抵抗中的直接作用
影响因子：
56.9
作者：
HOTAMISLIGIL, GS;SHARGILL, NS;SPIEGELMAN, BM
通讯作者：
SPIEGELMAN, BM
影响因子：
29
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Biddinger, Sudha B.;Hernandez-Ono, Antonio;Kahn, C. Ronald
通讯作者：
Kahn, C. Ronald
影响因子：
13.5
作者：
Crespo, J;Cayón, A;Pons-Romero, F
通讯作者：
Pons-Romero, F
影响因子：
9.8
作者：
Brunt, EM;Janney, CG;Bacon, BR
通讯作者：
Bacon, BR