Fernández-López José-Antonio, Remesar Xavier, Foz Màrius, Alemany Marià
Centre Especial de Recerca en Nutrició i Ciència dels Aliments, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
Drugs. 2002;62(6):915-44. doi: 10.2165/00003495-200262060-00005.
The high incidence of obesity, its multifactorial nature, the complexity and lack of knowledge of the bodyweight control system, and the scarcity of adequate therapeutics have fuelled anti-obesity drug development during a considerable number of years. Irrespective of the efforts invested by researchers and companies, few products have reached a minimum level of effectiveness, and even fewer are available in medical practice. As a consequence of anti-obesity research, our knowledge of the bodyweight control system increased but, despite this, the pharmacological approaches to the treatment of obesity have not resulted yet in effective drugs. This review provides a panoramic of the multiple different approaches developed to obtain workable drugs. These approaches, however, rely in only four main lines of action: control of energy intake, mainly through modification of appetite;control of energy expenditure, essentially through the increase of thermogenesis;control of the availability of substrates to cells and tissues through hormonal and other metabolic factors controlling the fate of the available energy substrates; andcontrol of fat reserves through modulation of lipogenesis and lipolysis in white adipose tissue. A large proportion of current research is centred on neuropeptidic control of appetite, followed by the development of drugs controlling thermogenic mechanisms and analysis of the factors controlling adipocyte growth and fat storage. The adipocyte is also a fundamental source of metabolic signals, signals that can be intercepted, modulated and used to force the brain to adjust the mass of fat with the physiological means available. The large variety of different approaches used in the search for effective anti-obesity drugs show both the deep involvement of researchers on this field and the large amount of resources devoted to this problem by pharmaceutical companies. Future trends in anti-obesity drug research follow closely the approaches outlined; however, the increasing mass of information on the molecular basis of bodyweight control and obesity will in the end prevail in our search for effective and harmless anti-obesity drugs.
肥胖症的高发病率、其多因素性质、体重控制系统的复杂性和知识匮乏，以及合适治疗方法的稀缺，在相当长的时间里推动了抗肥胖药物的研发。尽管研究人员和公司投入了大量努力，但很少有产品达到最低有效水平，在医学实践中可用的产品更是少之又少。作为抗肥胖研究的结果，我们对体重控制系统的了解有所增加，然而，尽管如此，肥胖症的药物治疗方法尚未产生有效的药物。本综述全面介绍了为获得可行药物而开发的多种不同方法。然而，这些方法仅依赖于四条主要作用途径：控制能量摄入，主要通过改变食欲；控制能量消耗，主要通过增加产热；通过激素和其他代谢因素控制可用能量底物的命运，从而控制细胞和组织对底物的利用；以及通过调节白色脂肪组织中的脂肪生成和脂肪分解来控制脂肪储备。目前的大部分研究集中在神经肽对食欲的控制上，其次是控制产热机制的药物开发以及对控制脂肪细胞生长和脂肪储存的因素的分析。脂肪细胞也是代谢信号的重要来源，这些信号可以被拦截、调节并用于促使大脑利用可用的生理手段来调整脂肪量。在寻找有效的抗肥胖药物过程中使用的各种不同方法，既显示了研究人员在该领域的深入参与，也显示了制药公司为解决这个问题投入的大量资源。抗肥胖药物研究的未来趋势紧密遵循上述方法；然而，关于体重控制和肥胖症分子基础的信息量不断增加，最终将在我们寻找有效且无害的抗肥胖药物的过程中占据主导地位。
