Long non-coding RNAs could act as vectors for paternal heredity of high fat diet-induced obesity

// Tian An 1, * , Teng Zhang 2, * , Fei Teng 1 , Jia-Cheng Zuo 1 , Yan-Yun Pan 1 , Yu-Fei Liu 3 , Jia-Nan Miao 1 , Yu-Jie Gu 1 , Na Yu 1 , Dan-Dan Zhao 1 , Fang-Fang Mo 1 , Si-Hua Gao 1 and Guangjian Jiang 1 1 Diabetes Research Center, Beijing University of Chinese Medicine, Beijing, China 2 State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China 3 The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China * These authors have contributed equally to this work Correspondence to: Si-Hua Gao, email: sihuagaopaper@sina.com Guangjian Jiang, email: guangjianjiang@sina.com Keywords: long non-coding RNA, paternal inheritance, genetic vector, obesity Received: April 03, 2017 Accepted: April 24, 2017 Published: May 24, 2017 ABSTRACT Long non-coding RNAs (lncRNAs) play an important role in epigenetic regulation, and abnormalities may lead to male infertility. To investigate whether lncRNAs are involved in intergenerational inheritance of obesity and obesity-induced decline in fertility, we divided mice into obesity (F0 mice fed a high-fat diet, F0-HFD) and non-obese (F0 mice fed normal chow, F0-NC) model groups and their male offspring (F1-HFD and F1-NC, respectively). We examined the differences in the expression levels of lncRNAs and mRNAs in the F0-HFD/F0-NC and F1-HFD/F1-NC groups. The results revealed similar expression patterns in the F1-HFD/F0-HFD groups at both the lncRNA and mRNA levels. The maximum difference in the lncRNA expression was observed between the F0-HFD and F0-NC groups. The differentially expressed lncRNA targets and mRNAs identified in our study are mainly involved in GnRH signalling pathway, metabolic process, and Hippo signalling pathway; similarly expressed lncRNAs and mRNAs in F1-HFD/F0-HFD are closely linked with G-protein coupled receptor signalling pathway, pancreatic polypeptide receptor activity, and lysine biosynthesis, which may play an important role in the molecular mechanism of intergenerational inheritance of obesity. Furthermore, potential genes that might play important roles in the pathogenesis of obesity-related low fertility were revealed by lncRNA-and mRNA-interaction studies based on the microarray expression profiles. In conclusion, we found that lncRNA could be involved in obesity-induced infertility by expressing abnormalities, which could act as genetic vectors of paternal inheritance of obesity.