A modification to DNA called methylation has been connected to obesity. It is known that many changes are made to genes throughout life, called epigenetic modifications. Researchers began to learn a lot more about epigenetics in the past ten years; these chemical alterations have been found to affect DNA and RNA, and there are many different types of these modifications. The study of these changes has grown into an entire field, and they've has been linked to many fundamental physiological processes, such as specification of cell types, and disease states like cancer. This latest research has indicated that an epigenetic modification that adds methyl groups to genes, could contribute to a reduction in muscle mass, and metabolic disruptions like the ones seen in obese states.
The video above summarizes the work, which was published in BMC Medicine. The work was led by Cajsa Davegardh, a doctoral student at Lund University. The study looked at the different methylation characteristics of muscle stem cell DNA in obese and in healthy individuals.
"Many genes that had changed their genetic expression also changed their degree of methylation during the development to mature muscle cells, which indicates a connection," Davegardh revealed.
The investigators learned that a gene that aggravates inflammation, IL-32 has an important role in sensitivity to insulin and gene maturation in muscle cells that have matured completely. Disruption of insulin sensitivity is a common feature of obesity, and is a major risk factor for the development of diabetes. When the scientists manipulated the level of the gene, they saw an impact. "By reducing the gene expression, the muscle's insulin sensitivity was increased," said Davegardh.
Evaluating the differences in DNA methylation states in obese individual muscle stem cells compared to muscle stem cells of people with a weight in the normal range, the scientists found differences in the genes that were being regulated during the maturation of the cell. They also saw that alterations in methylation patterns were more frequent in the obese people when compared to non-obese people.
"We believe that in obese individuals the muscle stem cells have been reprogrammed, and that this may partly explain why muscle cells in obese people have decreased insulin sensitivity and lower metabolism after they have matured," Davegardh explained. "They may also have a protective function. Furthermore, we don't know what happens when you lose weight -- whether the methylations are restored. This would be interesting to follow up."
Many environmental influences seem to exert an epigenetic effect, like pollution, pesticides, heavy metals, radioactivity, viruses and bacteria, to name a few. There are a variety of different kinds of epigenetic modifications other than methylation such as acetylation, phosphorylation, sumolyation and ubiquitylation. Epigenetic mechanisms have been linked to a wide range of disorders affecting many organ systems like the cardiovascular, respiratory, reproductive and immune systems, as well as neurobehavioral and cognitive diseases and practically every kind of cancer. As research in this area progresses, we are sure to learn a lot more. The video below features a talk on epigenetics from molecular biologist Nessa Carey, presented by The Royal Institution.