Obesity can reprogram muscle stem cells

In a new study, doctoral student Cajsa Davegårdh has studied so-called DNA methylation in muscle stem cells in both obese and non-obese individuals. DNA methylation is an epigenetic process in which small molecules – methyl groups –are added to genes and fine-tune the gene’s activity, like a dimmer switch.

By comparing the DNA methylation in immature and mature muscle cells from healthy individuals, Cajsa Davegårdh discovered that the actual degree of methylation had a major impact on the maturation process.

A pro-inflammatory gene, IL-32, turned out to be particularly important with regard to the maturation process and the insulin sensitivity of the fully developed muscle cell. Impaired insulin sensitivity is common in obesity and is a risk factor for type 2 diabetes.

“By reducing the gene expression, the muscle’s insulin sensitivity was increased”, says Cajsa Davegårdh.

These findings were confirmed by experiments on mice.

Difference between slim and obese individuals

Cajsa Davegårdh then compared the differences in DNA methylation in muscle stem cells from obese individuals (BMI over 30) and individuals of normal weight. She discovered that partly different genes were regulated during the maturation process and that methylation changes were significantly more common in subjects who were obese compared to those who were non-obese.

However, the cause and effect – i.e. whether the methylations are caused by obesity or the methylations increase the risk of becoming obese – can so far not be 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.”