Maintaining a healthy weight requires balancing energy intake with expenditure. A variety of elements influence how physically active we are, including genetic, cultural, and environmental factors. Evidence from a new study suggests that epigenetic changes in agouti-related proteins may regulate voluntary exercise behavior in mice.

Agouti-related proteins are neuropeptides produced primarily in the hypothalamus. They regulate appetite, metabolism, and energy expenditure.

Epigenetic changes are biological mechanisms that regulate gene expression (how and when certain genes are turned on or off). DNA methylation – the addition of methyl groups to the nucleotide bases of DNA – is a common epigenetic change. Previous research has shown that DNA methylation influences hypothalamic development in mice at specific time points early in life.

In this study, transgenic mice that lacked the enzymes that facilitate DNA methylation in agouti-related proteins developed a sedentary phenotype later in life. This was manifested by low energy output in the form of voluntary exercise, with the transgenic mice running roughly half the distance on exercise wheels as their wild type counterparts.

These findings point to the complexity of identifying ways to motivate people to exercise as a means to regulate body weight.

• Link to full study.