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

<div><p>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 <i>ad libitum</i>. 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.</p></div

Expression of protein coding genes and miRNAs in skeletal muscle.

<p>Protein coding genes (A) and miRNA (B) with a fold change of > ±1.5 and significant differential expression with a p value < 0.05 (Student´s t test) are shown. The fold change (Obese/Lean) for each significant gene is shown. A positive fold change denotes upregulation in obese Göttingen minipigs and a negative denotes downregulation in obese Göttingen minipigs.</p

miRNA-target interactions.

<p>miRNA-target interactions.</p

Expression of protein coding genes and miRNAs in adipose tissue.

<p>(A) Protein-coding genes and (B) miRNAs with a fold change of > ±1.5 and significant differential expression with a p value < 0.05 (Student´s t test) are shown. The fold change (Obese/Lean) for each significant gene is shown. A positive fold change denotes upregulation in obese Göttingen minipigs and a negative fold change denotes down regulation in obese Göttingen minipigs.</p

Expression of protein coding genes and miRNAs in liver.

<p>A) Protein-coding genes and (B) miRNAs with a fold change of > ±1.5 and significant differential expression with a p value < 0.05 (Student´s t test) are shown. The fold change (Obese/Lean) for each significant gene is shown. A positive fold change denotes upregulation in obese Göttingen minipigs and a negative fold change denotes downregulation in obese Göttingen minipigs.</p

RAIN v1

<div><b>RAIN: RNA–protein Association and Interaction Networks</b></div><div><br></div><div>RAIN integrates non-coding RNA (ncRNA) and protein interaction networks in an easily accessible web interface. </div><div>It contains three types of ncRNA associations: microRNA-target, ncRNA-protein and ncRNA-ncRNA interactions and combines them with protein-protein interaction available in the STRING database. ncRNA associations cover four model organisms and are extracted from experimental data, automatic literature mining and curated examples. For miRNAs, we further include precomputed target predictions. </div