UVA reearch: Mice doing tiny squats could power us to an ‘exercise pill’

Weightlifting mice doing tiny squats are giving us big gains in our understanding of how exercise helps prevent diabetes and benefits health.

Zhen Yan, PhD, a preeminent exercise researcher at the University of Virginia School of Medicine, has developed an innovative mouse model of exercise that will let scientists better understand how resistance training affects the muscles and the metabolic processes in the body. By understanding these metabolic changes, doctors may one day be able to duplicate these benefits through medication for people who can’t exercise – an exercise pill, basically.

“It is every exercise scientist’s dream to use an animal model to dig deep into the underlying mechanisms of exercise. This novel mouse model made it a reality to study resistance exercise, a type exercise that is equally if not more important than aerobic exercise to all of us, in an unprecedent manner,” said Yan, director of the Center for Skeletal Muscle Research at UVA’s Robert M. Berne Cardiovascular Research Center. “This will for sure accelerate research, and the findings will foster development of new therapeutics for many health problems.”

The squat is considered one of the kings of muscle-building exercises, and it is a staple for many bodybuilders. Squats work the leg muscles, including the quadriceps, hamstrings and calves, but also the glutes, core and even the back. Done right, they offer a potent workout, and that’s one reason many gym-goers like to skip them.

Yan cleverly invented a setup to get mice to do squats of their own accord, something even New Year’s resolutioners often struggle with. He made it so that when the mice are pumping iron, they are also pumping up their bellies. In essence, the mice meet resistance when standing up to get food. This recruits the same muscles as in the squat. The more they want to eat, the more squats they do. The researchers can vary the load as needed.

The model represents a significant improvement over the existing resistance exercise model because there is no need for frequent handling of the mice. That limitation made it impossible for scientists to do large-scale studies that they can now carry out easily.

The model has already yielded important insights. In addition to the expected increases in muscle size and power, regular strength training “profoundly improved” blood sugar management throughout the body and enhanced insulin sensitivity in skeletal muscle, Yan found. Both are important factors in managing and preventing diabetes. In addition, regular weight training enhanced the natural removal of dead cells and cellular debris, an important process in maintaining good health.

“The findings are truly the tip of the iceberg but reveal multi-faceted, distinct impacts of weight training,” Yan said. “Our hope is that we and many researchers in the scientific community can use this model to unveil the effective exercise secrets to benefit the general public.”

Yan has described the new model in an article in the FASEB Journal, a publication of the Federation of American Societies for Experimental Biology. The research team consisted of Di Cui, Joshua C. Drake, Rebecca J. Wilson, Robert J. Shute, Bevan Lewellen, Mei Zhang, Henan Zhao, Olivia L. Sabik, Suna Onengut, Stuart S. Berr, Stephen S. Rich, Charles R. Farber and Yan.

The research was supported by the National Institutes of Health, grant AR050429.

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