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

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.

The expression signatures in liver and adipose tissue from obese Göttingen Minipigs reveal a predisposition for healthy fat accumulation

“…Both the histopathological findings and the results of the expression studies clearly document that the FFC diet challenged the metabolism in the liver. That diet rather than obesity per se is the driving factor is supported by a previous study in which hepatic differential expression between Göttingen Minipigs fed standard minipig chow restrictively (lean controls) and Göttingen Minipigs fed the same diet ad libitum (obese) was studied 20 . Although, these treatments resulted in an obese group obtaining roughly the same body weight as the FFC diet groups included in this study, liver metabolism was far from affected at the level documented here, indicating that the diet components play a more important role than obesity per se.…”

Genetic architecture and regulatory impact on hepatic microRNA expression linked to immune and metabolic traits

“…miR-34a is an obesity-associated miRNA that attenuates metabolic hormone function [ 39 , 40 ]. It is upregulated in the Doroc pig and Göttingen Minipig obesity model [ 41 , 42 ]. In other cases, miR-34a expression has been found to be increased in human patients with liver disease and in a rat liver fibrosis model [ 43 , 44 ].…”

Genome-Wide Identification of RNA Editing Sites Affecting Intramuscular Fat in Pigs

“…ssc-miR-15b, ssc-miR-16, ssc-miR-103, and ssc-miR-221-3p were reported to have different expressions in the myofiber between lean and obese pig breeds [ 51 ]. ssc-miR-16 was also reported to be upregulated in the muscle of obese minipigs [ 52 ]. ssc-miR-103 and ssc-miR-221-3p are associated with meat quality [ 53 ].…”