"Compound 14" mimics the effects of exercise without setting foot in the gym
Enjoying the health benefits of a back-breaking workout without actually working out sure is a tantalizing prospect. This goes a long way to explaining the torrent of exercise equipment that promises to do more for our figures with less of our sweat and tears, and recently, the development of drugs that could imitate the beneficial effects of exercise. The latest advance in this area is the development of a molecule that mimics the effects of exercise by influencing the metabolic process, giving it the potential to treat type 2 diabetes and obesity.
The scientists at the University of Southampton who developed the molecule initially set out to target the central energy sensor in cells called AMPK. Pointing to previous research, the team believed that if a small molecule could be used to selectively activate AMPK, it could boost the uptake of glucose and oxygen in the cells by mimicking the effects of exercise.
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The small molecule, dubbed "compound 14", works by inhibiting the function of a cellular enzyme involved in metabolism called ATIC. This causes an accumulation of another molecule in the cells called ZMP, which tricks the cells into acting as if they are running out of energy, kicking AMPK into action to trigger the cells to increase glucose uptake and metabolism.
Compound 14 was given to two sets of mice, with one group fed a regular diet and the other fed high-fat foods so as to make them obese and intolerant to glucose, a symptom of pre-diabetes. The weight of the healthy mice remained the same after treatment with compound 14, as did their blood glucose levels. Meanwhile, the heightened blood glucose levels in the obese mice was reduced to near-normal levels after just a single dose of compound 14.
Taking things a step further, the team treated the obese mice with compound 14 for seven days and found that it improved their glucose tolerance and also shaved 1.5 g (0.05 oz), or around five percent, off their body weight. Subjecting the healthy mice to the same treatment brought about no changes in weight.
Compound 14 joins a host of other potential drugs that could be used to tackle bad health. In 2013, a drug under development at The Scripps Institute was found to increase the metabolic activity in skeletal muscles of mice, improving their muscle mass and fitness. We've also seen exercise-mimicking drugs that promise to better transform white fat into brown and ones that promise to reverse age-dependent diabetes.
The University of Southampton researchers will now continue to develop compound 14 and study the effects of long-term treatment. If it proves safe, the researchers say a drug could be developed aimed at those suffering diabetes and obesity.
The research was published in the journal Chemistry and Biology.
Source: University of Southampton