Geyer G
Ludwig Boltzmann-Institut für Experimentelle Endokrinologie, Wien.
Acta Med Austriaca. 1998;25(4-5):117-25.
This review explains and surveys very recent findings and experimental results concerning molecular pathology and genetics of overweight and obesity and also evaluates their relevance for the actual treatment of obesity at present. Most of these studies were done on inbred obese mice or rats and it is yet unknown to what extent the results do apply to human overweight. Nevertheless these studies led to the discovery of a new hormone--OB-protein or leptin--produced by adipocytes of animals. It does not only increase satiety by influencing feeding centers and decrease body weight but it also interferes with several peripheral metabolic functions. Mutations of leptin expression or expression of leptin receptors as observed in animals are, however, very rare in humans. In obese individuals (and animals) there is a yet unexplained resistance to the effects of leptin which interferes with successful therapeutic use of leptin in human obesity. Various other recently discovered transmitters modifying feeding habits may, however, become targets of future drugs making dietary weight loss and its maintenance more acceptable and successful. At present obese people and patients have to rely, however, on traditional methods of weight loss though these are known to yield poor results over prolonged periods of time. Orlistat, a recently introduced drug results in malabsorption of fat from the gut by inhibiting lipases. Though it is not based on recent insights to regulation of body weight it is promising primarily for educating patients to reduce their nutritional fat intake.
本综述解释并概述了关于超重和肥胖的分子病理学及遗传学的最新研究发现和实验结果,并评估了它们与当前肥胖实际治疗的相关性。这些研究大多是在近交系肥胖小鼠或大鼠上进行的,目前尚不清楚这些结果在多大程度上适用于人类超重情况。然而,这些研究导致发现了一种由动物脂肪细胞产生的新激素——OB蛋白或瘦素。它不仅通过影响进食中枢增加饱腹感并减轻体重,还会干扰多种外周代谢功能。不过,在动物中观察到的瘦素表达或瘦素受体表达的突变在人类中非常罕见。在肥胖个体(和动物)中,对瘦素的作用存在一种尚未解释清楚的抵抗,这干扰了瘦素在人类肥胖治疗中的成功应用。然而,最近发现的各种其他改变饮食习惯的递质可能会成为未来药物的作用靶点,使饮食减肥及其维持变得更容易接受且更成功。目前,肥胖人群和患者不得不依赖传统的减肥方法,尽管众所周知这些方法长期效果不佳。奥利司他是一种最近推出的药物,它通过抑制脂肪酶导致肠道脂肪吸收不良。虽然它并非基于对体重调节的最新见解,但主要有望促使患者减少营养性脂肪摄入。