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DOI | 10.1371/journal.pone.0214387 |
Lipidomic and transcriptomic analysis of western diet-induced nonalcoholic steatohepatitis (NASH) in female LdIr(-/-) mice | |
Garcia-Jaramillo, Manuel1,2,3; Spooner, Melinda H.1,2; Lohr, Christiane V.4; Wong, Carmen P.1,2; Zhang, Weijian2; Jump, Donald B.1,2 | |
发表日期 | 2019 |
ISSN | 1932-6203 |
卷号 | 14期号:4 |
英文摘要 | Background Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, particularly in obese and type 2 diabetic individuals. NAFLD ranges in severity from benign steatosis to nonalcoholic steatohepatitis (NASH); and NASH can progress to cirrhosis, primary hepatocellular carcinoma (HCC) and liver failure. As such, NAFLD has emerged as a major public health concern. Herein, we used a lipidomic and transcriptomic approach to identify lipid markers associated with western diet (WD) induced NASH in female mice. Methods Female mice (low-density lipoprotein receptor null (LdIr(-/-)) were fed a reference or WD diet for 38 and 46 weeks. Transcriptomic and lipidomic approaches, coupled with statistical analyses, were used to identify associations between major NASH markers and transcriptomic & lipidomic markers. Results The WD induced all major hallmarks of NASH in female Ldlr(-/-)r mice, including steatosis (SFA, MUFA, MUFA-containing di- and triacylglycerols), inflammation (TNF alpha), oxidative stress (Ncf2), and fibrosis (Coll A). The WD also increased transcripts associated with membrane remodeling (LpCat), apoptosis & autophagy (Caspl, CtsS), hedgehog (Taz) & notch signaling (Hey1), epithelial-mesenchymal transition (S1004A) and cancer (Gpc3). WD feeding, however, suppressed the expression of the hedgehog inhibitory protein (Hhip), and enzymes involved in triglyceride catabolism (Tgh/Ces3, Ces1 g), as well as the hepatic abundance of C18-22 PUFA-containing phosphoglycerolipids (GpCho, GpEtn, GpSer, Gpins). WD feeding also increased hepatic cyclooxygenase (Cox1 & 2) expression and pro-inflammatory omega 6 PUFA-derived oxylipins (PGE2), as well as lipid markers of oxidative stress 8-iso-PGF2 alpha). The WD suppressed the hepatic abundance of reparative oxylipins (19, 20-DiHDPA) as well as the expression of enzymes involved in fatty epoxide metabolism (Cyp2C, Ephx). Conclusion WD-induced NASH in female LdIr(-/-) mice was characterized by a massive increase in hepatic neutral and membrane lipids containing SFA and MUFA and a loss of C18-22 PUFA-containing membrane lipids. Moreover, the WD increased hepatic pro-inflammatory oxylipins and suppressed the hepatic abundance of reparative oxylipins. Such global changes in the type and abundance of hepatic lipids likely contributes to tissue remodeling and NASH severity. |
WOS研究方向 | Science & Technology - Other Topics |
来源期刊 | PLOS ONE |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/96305 |
作者单位 | 1.Oregon State Univ, Sch Biol & Populat Hlth Sci, Nutr Program, Corvallis, OR 97331 USA; 2.Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA; 3.Oregon State Univ, Dept Chem, Gilbert Hall 153, Corvallis, OR 97331 USA; 4.Oregon State Univ, Carlson Coll Vet Med, Anat Pathol, Corvallis, OR 97331 USA |
推荐引用方式 GB/T 7714 | Garcia-Jaramillo, Manuel,Spooner, Melinda H.,Lohr, Christiane V.,et al. Lipidomic and transcriptomic analysis of western diet-induced nonalcoholic steatohepatitis (NASH) in female LdIr(-/-) mice[J],2019,14(4). |
APA | Garcia-Jaramillo, Manuel,Spooner, Melinda H.,Lohr, Christiane V.,Wong, Carmen P.,Zhang, Weijian,&Jump, Donald B..(2019).Lipidomic and transcriptomic analysis of western diet-induced nonalcoholic steatohepatitis (NASH) in female LdIr(-/-) mice.PLOS ONE,14(4). |
MLA | Garcia-Jaramillo, Manuel,et al."Lipidomic and transcriptomic analysis of western diet-induced nonalcoholic steatohepatitis (NASH) in female LdIr(-/-) mice".PLOS ONE 14.4(2019). |
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