title: Overexpression of miR-155 in the liver of transgenic mice alters the expression profiling of hepatic genes associated with lipid metabolism.
abstract: Hepatic expression profiling has revealed miRNA changes in liver diseases, while hepatic miR-155 expression was increased in murine non-alcoholic fatty liver disease, suggesting that miR-155 might regulate the biological process of lipid metabolism. To illustrate the effects of miR-155 gain of function in transgenic mouse liver on lipid metabolism, transgenic mice (i.e., Rm155LG mice) for the conditional overexpression of mouse miR-155 transgene mediated by Cre/lox P system were firstly generated around the world in this study. Rm155LG mice were further crossed to Alb-Cre mice to realize the liver-specific overexpression of miR-155 transgene in Rm155LG/Alb-Cre double transgenic mice which showed the unaltered body weight, liver weight, epididymal fat pad weight and gross morphology and appearance of liver. Furthermore, liver-specific overexpression of miR-155 transgene resulted in significantly reduced levels of serum total cholesterol, triglycerides (TG) and high-density lipoprotein (HDL), as well as remarkably decreased contents of hepatic lipid, TG, HDL and free fatty acid in Rm155LG/Alb-Cre transgenic mice. More importantly, microarray data revealed a general downward trend in the expression profile of hepatic genes with functions typically associated with fatty acid, cholesterol and triglyceride metabolism, which is likely at least partially responsible for serum cholesterol and triglyceride lowering observed in Rm155LG/Alb-Cre mice. In this study, we demonstrated that hepatic overexpression of miR-155 alleviated nonalcoholic fatty liver induced by a high-fat diet. Additionally, carboxylesterase 3/triacylglycerol hydrolase (Ces3/TGH) was identified as a direct miR-155 target gene that is potentially responsible for the partial liver phenotypes observed in Rm155LG/Alb-Cre mice. Taken together, these data from miR-155 gain of function study suggest, for what we believe is the first time, the altered lipid metabolism and provide new insights into the metabolic state of the liver in Rm155LG/Alb-Cre mice.
authors: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors: Xiaolin
authors: X
authors: Lin
authors: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors: Junshuang
authors: J
authors: Jia
authors: Department of Endocrinology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
authors: Tao
authors: T
authors: Du
authors: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors: Wei
authors: W
authors: Li
authors: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors: Xiaoyan
authors: X
authors: Wang
authors: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors: Jieqiong
authors: J
authors: Wei
authors: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors: Xia
authors: X
authors: Lin
authors: Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Hui
authors: H
authors: Zeng
authors: Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors: Longping
authors: L
authors: Yao
authors: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
authors: Xuebing
authors: X
authors: Chen
authors: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
authors: Jingshen
authors: J
authors: Zhuang
authors: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors: Jie
authors: J
authors: Weng
authors: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors: Yu
authors: Y
authors: Liu
authors: Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou, China.
authors: Jihong
authors: J
authors: Lin
authors: Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou, China.
authors: Qinghong
authors: Q
authors: Wu
authors: Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou, China.
authors: Wanshan
authors: W
authors: Wang
authors: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors: Kaitai
authors: K
authors: Yao
authors: Department of General Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
authors: Kang
authors: K
authors: Xu
authors: Cancer Research Institute, Southern Medical University, Guangzhou, China; Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou, China.
authors: Dong
authors: D
authors: Xiao
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D020869:Gene Expression Profiling; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D008055:Lipids; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D012333:RNA, Messenger