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Significance We have developed a method for finding pharmaceuticals that would treat obesity and type 2 diabetes by increasing the metabolic rate of resting skeletal muscle. The metabolic rate is increased by shifting the motor protein myosin from a low activity state to a higher activity state. We devised an assay, screened for compounds, and found one molecule, piperine. Piperine increased the metabolic rate of resting muscle fibers. Piperine does not have the properties required to be a pharmaceutical in humans, but it would make a good lead compound for finding compounds that do. Our results provide proof of concept that these metabolic diseases can be treated by future pharmaceuticals that target myosin to increase the metabolism of excess calories.
Nogara et al. (Mon,) studied this question.