Sichuan Agricultural University and LC Sciences Uncover the Epigenetics of Obesity

30-May-2012 - China

In a study published in Nature Communications, researchers from Sichuan Agricultural University and LC Sciences report the miRNAome in porcine adipose and muscle tissues. The report provides a valuable epigenomic source for obesity prediction and prevention and furthers the development of pig as a model organism for human obesity research.

Scientists now know that the genetic code alone isn’t responsible for adult phenotype or even the offspring of these adults. Epigenetics refers to changes in gene expression affecting phenotype that don’t involve changes to the DNA nucleotide sequence itself, and yet are heritable. DNA methylation, histone modification and microRNA (miRNA) expression are examples of epigenetic mechanisms that have recently been identified as important regulators of gene expression in many biological systems.

A team led by Researchers at the Institute of Animal Genetics and Breeding, Sichuan Agricultural University, China has used a pig model to investigate the systematic association between epigenetic regulators and obesity. Pigs are an excellent model system to study obesity due to their similar physiology to ours including: metabolic features, cardiovascular systems, and proportional organ sizes. The researchers generated a genome-wide DNA methylation map as well as miRNA expression and gene expression maps for adipose and muscle tissues from three pig breeds living within comparable environments but displaying distinct fat levels.

The miRNA expression portion of this project was supported by team members from LC Sciences’ Hangzhou, China lab. LC Sciences has previously collaborated with the group from Sichuan Agricultural University. In 2010 they performed a comprehensive search for porcine miRNAs that extended the repertoire of pig miRNAome to 777 unique miRNAs and enabled an atlas of miRNA regulation functions and networks to be constructed which has laid the groundwork for future miRNA studies in pig models.

In the current study, numerous miRNAs having known or potential roles in obesity were identified. Additionally, the researchers found a differentially methylated region in males compared with females. This region is located in the promoter of a miRNA cluster that includes adjacent miR-99b, let-7e and miR-125a. Although no previous evidence exists for a direct relationship of these three miRNAs to obesity, the key functions and targets of these miRNAs potentially contribute to sexual differences in obesity development.

Dr. Qiulei Lang, Head of LC Sciences operations in Asia commented, ”miRNA has been a focus of LC Sciences’ since 2005. Back then we realized its importance and so have tailored our capabilities to support agricultural customers worldwide in their miRNA research. A proprietary RNA-Seq data analysis pipeline that was developed by LC Sciences enabled us to make sense of the tremendous amount of small RNA sequencing data that we generated in this study.”

That data analysis shows global epigenetic similarity and difference among breeds, sexes and anatomic locations. The epigenetically regulated regions in promoters are highly associated with obesity development via expression repression of both known obesity-related genes and novel genes. This comprehensive map provides a solid basis for exploring epigenetic mechanisms of obesity.

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