Molecular pathways to obesity
Molecular pathways to obesity
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DOI：
10.1038/sj.ijo.0802124
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发表时间：
2002-09-01
影响因子：
4.9
通讯作者：
Hofbauer, K
中科院分区：
文献类型：
--
作者：
Hofbauer, K
肥胖是由于能量摄入和能量消耗之间的长期不平衡造成的。环境因素，如高热量食物的增加或体力活动需求的减少，都有助于其发展，其影响因遗传易感性而被放大。近年来，对肥胖病理生理的认识取得了显著进展。虽然大多数关于能量平衡调节的见解都是在啮齿动物模型中获得的，但罕见的单基因肥胖临床病例为这些机制在人类中的重要性提供了证据。瘦素是一种源自脂肪组织的因子，并告知大脑能量储备的状态，这一发现坚定地确立了身体脂肪储存长期调节的概念。瘦素对肥胖患者的治疗效果令人失望，这可以解释为在进化过程中，这种激素与其说是作为肥胖信号，不如说是作为饥饿信号。可以想象，对瘦素下游机制的药理学干扰，例如黑素皮质素通路，可能在治疗上更有希望。脂肪细胞分化和增殖调控的新分子机制的发现及其旁分泌和内分泌功能的阐明，改变了脂肪组织作为甘油三酯惰性储存库的传统观点。新的解偶联蛋白的鉴定可以改变目前人类产热调节的概念。在能量平衡调节新靶点的识别方面取得的显著进展应该对寻找新的抗肥胖药物产生积极的影响。
Obesity results from a chronic imbalance between energy intake and energy expenditure. Environmental factors, such as the increased availability of high caloric food or the decreased need for physical activity, contribute to its development and their influence is amplified by genetic predisposition. In recent years remarkable progress has been made in the understanding of the pathophysiology of obesity. Although most of the insights into the regulation of energy balance have been obtained in rodent models, the rare clinical cases of monogenic obesity provided evidence for the importance of several of these mechanisms in humans. The identification of leptin as a factor originating from adipose tissue and informing the brain about the status of energy reserves firmly established the concept of long-term regulation of body fat stores. The disappointing therapeutic results with leptin in obese patients could be explained by the fact that during evolution this hormone developed rather as a starvation signal than as an adiposity signal. It is conceivable that the pharmacological interference with mechanisms downstream of leptin, for example with the melanocortin pathway, might be therapeutically more promising. The discovery of new molecular mechanisms involved in the regulation of the differentiation and proliferation of adipocytes and the elucidation of their paracrine and endocrine functions have changed the traditional view of adipose tissue as an inert depot for triglycerides. The identification of new uncoupling proteins could modify the current concepts of the regulation of thermogenesis in humans. The remarkable progress in the identification of novel targets involved in the regualtion of energy balance should have a positive impact on the search for new antiobesity agents.