Summary: Study identifies a specific gene in rats that relates to physical inactivity. The gene could play a role in human sedentary behaviors.
Source: University of Missouri
Regular physical activity is a crucial part of living a healthy lifestyle. However, a majority of American adults spend their waking hours sitting, which leads to a variety of health issues such as obesity, cardiovascular disease and cancer.
Now, a researcher from the University of Missouri has identified a specific gene related to physical inactivity in rats that could potentially play a role in sedentary behavior in humans as well.
“Previous research has shown us that genes play some role in physical inactivity,” said Frank Booth, a professor in the MU College of Veterinary Medicine.
“As inactivity leads to chronic disease, we wanted to identify which genes were involved and discovered one in particular, the Protein Kinase Inhibitor Alpha gene, that played a significant role.”
In 2009, Booth took 80 male rats and bred them with 80 female rats. He then placed the rats in voluntary running wheels, similar to those sold in pet stores, and tracked which rats ran the most and least. Over the past decade, Booth selectively bred the highly active rats with each other as well as the “lazy” rats with each other to determine if there is a difference in their genetic makeup. Booth found that the Protein Kinase Inhibitor Alpha gene was significantly less present in the “lazy” rats.
“What makes gene therapy difficult is that most chronic diseases are not caused by just one gene,” Booth said. “For example, there are more than 150 gene variations involved in type 2 diabetes. However, this study is paving the way for future research to identify other genes that might be involved in physical inactivity in humans as well.”
According to government data, costs associated with physical inactivity total $138 billion and account for more than 11% of total health care expenditures. In addition to the financial benefits of a more physically active society, Booth says a better understanding of genetic makeup could help public health officials see physical inactivity as a crucial priority to address.
“Physical inactivity contributes to more than 40 chronic diseases,” Booth said. “Rather than focusing on ways to treat chronic diseases after they have already developed, understanding the contributing factors to physical inactivity could help prevent those chronic diseases from occurring in the first place.”
University of Missouri
Brian Consiglio – University of Missouri
The image is in the public domain.
Original Research: Open access
“Overexpression of Protein Kinase Inhibitor Alpha Reverses Rat Low Voluntary Running Behavior”. Frank Booth et al.
Molecular Neurobiology doi:10.1007/s12035-018-1171-0
Overexpression of Protein Kinase Inhibitor Alpha Reverses Rat Low Voluntary Running Behavior
A gene was sought that could reverse low voluntary running distances in a model of low voluntary wheel-running behavior. In order to confirm the low motivation to wheel-run in our model does not result from defects in reward valuation, we employed sucrose preference and conditioned place preference for voluntary wheel-access. We observed no differences between our model and wild-type rats regarding the aforementioned behavioral testing. Instead, low voluntary runners seemed to require less running to obtain similar rewards for low voluntary running levels compared to wild-type rats. Previous work in our lab identified protein kinase inhibitor alpha as being lower in low voluntary running than wild-type rats. Next, nucleus accumbens injections of an adenoviral-associated virus that overexpressed the protein kinase inhibitor alpha gene increased running distance in low voluntary running, but not wild-type rats. Endogenous mRNA levels for protein kinase inhibitor alpha, dopamine receptor D1, dopamine receptor D2, and Fos were all only lower in wild-type rats following overexpression compared to low voluntary runners, suggesting a potential molecular and behavioral resistance in wild-type rats. Utilizing a nucleus accumbens preparation, three intermediate early gene mRNAs increased in low voluntary running slices after dopamine receptor agonist SKF-38393 exposure, while wild-type had no response. In summary, the results suggest that protein kinase inhibitor alpha is a promising gene candidate to partially rescue physical activity in the polygenic model of low voluntary running. Importantly, there were divergent molecular responses to protein kinase inhibitor alpha overexpression in low voluntary runners compared to wild-type rats.