Blum Kenneth, Chen Thomas J H, Meshkin Brian, Downs B William, Gordon Cory A, Blum Seth, Mangucci Julie F, Braverman Eric R, Arcuri Vanessa, Deutsch Roger, Pons Manuel-Martinez-
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, United States.
Med Hypotheses. 2007;68(4):844-52. doi: 10.1016/j.mehy.2006.08.041. Epub 2006 Oct 27.
Obesity is the second largest cause of preventable death in the United States. Historically, obesity was considered a behavioral problem that could be simply addressed with behavioral modifications in diet and exercise. As scientific advancements have demonstrated in other neurological healthcare conditions such as alcoholism, there are important biological and genetic components that limit the efficacy of behavioral adjustments alone. In light of data suggesting frequent co-morbidities to obesity, including diabetes mellitus, atherosclerosis, osteoporosis, and potentially others, we hypothesize that the biologic and genetic factors, synergistically with behavioral modifications, must be addressed to adequately treat this disease. We hypothesize that one such genetic factor that influences behavior and thus obesity is a predisposition to glucose craving and the overall effect of dopaminergic activity in the reward center of the brain. This defect drives individuals to engage in activities of behavioral excess, which will increase brain dopamine function, for which we have created the term reward deficiency syndrome (RDS) to categorize such biological influences on behavior. Consuming large quantities of alcohol or carbohydrates (carbohydrate bingeing) stimulates the brain's production of and utilization of dopamine. So too does the intake of crack/cocaine and the abuse of nicotine. We are proposing that a novel approach to nutritional supplementation may be required to target the RDS role in obesity. In this regard, Genotrim, a DNA based customized nutraceutical has been designed and is currently under investigation in several clinical studies. This is the first hypothesis paper whereby this new paradigm shift in thinking about obesity is presented.
肥胖是美国可预防死亡的第二大原因。从历史上看,肥胖被视为一个行为问题,可以通过饮食和运动方面的行为调整来简单解决。正如科学进步在其他神经疾病(如酗酒)中所表明的那样,存在重要的生物学和遗传因素,这些因素限制了仅靠行为调整的效果。鉴于有数据表明肥胖常伴有多种共病,包括糖尿病、动脉粥样硬化、骨质疏松症以及可能的其他疾病,我们假设必须同时解决生物学和遗传因素,并结合行为调整,才能充分治疗这种疾病。我们假设,一种影响行为进而导致肥胖的遗传因素是对葡萄糖的渴望倾向以及大脑奖励中枢多巴胺能活动的总体影响。这种缺陷促使个体从事过度行为活动,这会增强大脑多巴胺功能,为此我们创造了“奖励缺乏综合征”(RDS)这一术语,以对这种对行为的生物学影响进行分类。大量饮酒或摄入碳水化合物(碳水化合物暴饮暴食)会刺激大脑产生和利用多巴胺。吸食快克/可卡因和滥用尼古丁也会如此。我们建议可能需要一种新的营养补充方法来针对RDS在肥胖中的作用。在这方面,Genotrim,一种基于DNA的定制营养保健品,已经设计出来,目前正在多项临床研究中进行调查。这是第一篇提出关于肥胖这种思维新范式转变的假说论文。