Mitochondrial Uncoupling as a Therapeutic Target in Obesity

描述（由申请人提供）：肥胖被认为是一种全国性和全球性的流行病，因为在美国大约65%的成年人被归类为超重或肥胖，如体重指数（BMI）所定义的。事实上，在2000年，人类达到了一个历史性的里程碑，在历史上第一次，超重的成年人人数超过了体重不足的人数。肥胖与几种心血管危险因素有关，累积起来被认为是代谢综合征。虽然肥胖与代谢综合征和心血管疾病的风险增加有关;因此，肥胖受试者的体重减轻已被证明可减少或逆转健康风险因素。从根本上说，无论减肥的方法如何，即使是适度的体重减轻也能持续降低或逆转风险因素。在20世纪30年代，人们认识到使用线粒体解偶联剂增加身体的基础代谢，直接导致稳定和快速的体重减轻。在此期间，线粒体解偶联剂2，4-二硝基苯酚（2，4-DNP）作为减肥补充剂在柜台上出售。它是迄今为止唯一一种被证明对减肥100%有效的化合物;然而，它最终被FDA从货架上撤下，因为人们经常过量服用该化合物以提高减肥率。为了克服这一挑战，我们开发了非碳基的“自整流”纳米级器件并获得专利，在这种器件中，我们可以具体地、逐步地设置解耦合能力，当达到解耦合能力时，将关闭器件以进一步传导质子。本申请的目的是进一步建立概念验证，并探索这些器械促进减肥的潜在用途。

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.