Joint Profiling of miRNAs and mRNAs Reveals miRNA Mediated Gene Regulation in the Göttingen Minipig Obesity Model

PLoS One. 2016 Nov 30;11(11):e0167285. doi: 10.1371/journal.pone.0167285. eCollection 2016.

Abstract

Obesity and its comorbidities are an increasing challenge for both affected individuals and health care systems, worldwide. In obese individuals, perturbation of expression of both protein-coding genes and microRNAs (miRNA) are seen in obesity-relevant tissues (i.e. adipose tissue, liver and skeletal muscle). miRNAs are small non-coding RNA molecules which have important regulatory roles in a wide range of biological processes, including obesity. Rodents are widely used animal models for human diseases including obesity. However, not all research is applicable for human health or diseases. In contrast, pigs are emerging as an excellent animal model for obesity studies, due to their similarities in their metabolism, their digestive tract and their genetics, when compared to humans. The Göttingen minipig is a small sized easy-to-handle pig breed which has been extensively used for modeling human obesity, due to its capacity to develop severe obesity when fed ad libitum. The aim of this study was to identify differentially expressed of protein-coding genes and miRNAs in a Göttingen minipig obesity model. Liver, skeletal muscle and abdominal adipose tissue were sampled from 7 lean and 7 obese minipigs. Differential gene expression was investigated using high-throughput quantitative real-time PCR (qPCR) on 90 mRNAs and 72 miRNAs. The results revealed de-regulation of several obesity and inflammation-relevant protein-coding genes and miRNAs in all tissues examined. Many genes that are known to be de-regulated in obese humans were confirmed in the obese minipigs and several of these genes have target sites for miRNAs expressed in the opposing direction of the gene, confirming miRNA-mediated regulation in obesity. These results confirm the translational value of the pig for human obesity studies.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Gene Expression Profiling*
  • MicroRNAs / genetics*
  • Obesity / genetics*
  • Organ Specificity
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Swine
  • Swine, Miniature*

Substances

  • MicroRNAs
  • RNA, Messenger

Grant support

The project was funded by the Danish Independent Research Council (DFF-1335-00127), Innovation Fund Denmark, Danish Center for Scientific Computing (DCSC, DelC). The lean minipigs were funded by the SHARE foundation and Danielsen’s Foundation. The obese minipigs were donated by Novo Nordisk A/S. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.