Mitochondrial Uncoupling as a Therapeutic Target in Obesity

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DESCRIPTION (provided by applicant): Obesity is recognized as a national and global epidemic, as approximately 65% of adults in the United States are classified as overweight or obese as defined by body mass index (BMI). In fact, in the year 2000, the human race reached a historical landmark, when for the first time in history the number of adults with excess weight surpassed the number of those who were underweight. Obesity is linked with several cardiovascular risk factors cumulatively recognized as the metabolic syndrome. While obesity is associated with increased risk for metabolic syndrome and cardiovascular disease; consequently, weight loss in obese subjects has been demonstrated to reduce or reverse health risk factors. Fundamentally, irrespective of the method by which weight loss occurs, even a modest reduction in body weight has been shown to consistently reduce or reverse risk factors. In the 1930s it was recognized that increasing the body's basal metabolism using mitochondrial uncouplers, directly resulted in steady and rapid weight loss. During this period the mitochondrial uncoupler 2,4-dinitophenol (2,4-DNP) was sold over the counter as a weight-loss supplement. It is the only compound to date that has been shown to be 100% effective for weight-loss; however it was eventually pulled from the shelves by the FDA as people were routinely overdosing on the compound in an effort to increase their rate of weight loss. To overcome this challenge, we have developed and patented non-carbon-based, "self-rectifying" nano-scale devices, in which we can specifically and step-wise set the uncoupling capacity that when reached shuts the device off to further proton conductance. The goal of the current application is to further establish proof of concept and to explore the potential use of these devices to promote weight loss.