Robaczyk M, Smiarowska M, Krzyzanowska-Swiniarska B
Oddziału Chorób Wewnetrznych, Szpitala MSW w Szczecinie.
Przegl Lek. 1997;54(5):348-52.
Obesity--an important problem in modern societies--is caused by energy balance dysregulation and produces numerous adverse effects on health. Recently a particular attention has been paid to molecular and physiological mechanisms in the development of obesity and to the signalling role of adipose tissue in energy stores maintenance on the hypothalamic level. Leptin, the obese gene product discovered in 1995, may play a key role in the feedback system between adipose tissue and the ventromedial nucleus of the hypothalamus (satiety centre). The level of ob gene expression in adipose tissue and plasma leptin concentrations in humans are highly correlated with BMI. So far no mutations in the ob gene in obese subjects have been reported therefore leptin molecule could be active. Despite markedly increased leptin levels found in obesity its central action decreasing food intake and increasing energy expenditure is hindered. Defective ob protein signalling to the brain may be due to receptor and post-receptor defects. Neuropeptide Y, the hypothalamic neurotransmitter involved in the maintaining of energy homeostasis, is a likely candidate for mediating leptin afferent signals. In adipose tissue, the level of ob mRNA is regulated by insulin and glucocorticoids--hormones responsible for glucose homeostasis as well as for the central regulation of feeding behaviour. Until now the character of interactions between leptin and other hormones that regulate energy balance is not known, neither is the exact nature of leptin hypothalamic receptor defect. Defining of the role of leptin in the regulation of satiety and energy expenditure will undoubtedly contribute to a better understanding of the pathogenesis of obesity and its related metabolic complications and may lead to a new treatment approach to human obesity based on leptin or its analogues. At present research work focuses on leptin receptor studies and on ob gene polymorphism and its expression in feeding disorders including obesity and anorexia nervosa. The ob gene is one of a few genes involved in energy balance, however, very promising one.
肥胖——现代社会中的一个重要问题——是由能量平衡失调引起的,并且会对健康产生诸多不利影响。最近,人们特别关注肥胖发生过程中的分子和生理机制,以及脂肪组织在下丘脑水平维持能量储备方面的信号传导作用。瘦素是1995年发现的肥胖基因产物,可能在下丘脑腹内侧核(饱食中枢)与脂肪组织之间的反馈系统中起关键作用。人体脂肪组织中ob基因的表达水平和血浆瘦素浓度与体重指数高度相关。到目前为止,尚未报道肥胖受试者的ob基因发生突变,因此瘦素分子可能具有活性。尽管在肥胖人群中发现瘦素水平显著升高,但其减少食物摄入和增加能量消耗的中枢作用却受到阻碍。ob蛋白向大脑的信号传导缺陷可能是由于受体和受体后缺陷所致。神经肽Y是参与维持能量稳态的下丘脑神经递质,可能是介导瘦素传入信号的候选物质。在脂肪组织中,ob mRNA的水平受胰岛素和糖皮质激素调节,这两种激素负责葡萄糖稳态以及进食行为的中枢调节。到目前为止,瘦素与其他调节能量平衡的激素之间相互作用的性质尚不清楚,瘦素下丘脑受体缺陷的确切性质也不清楚。明确瘦素在饱腹感和能量消耗调节中的作用,无疑将有助于更好地理解肥胖及其相关代谢并发症的发病机制,并可能导致基于瘦素或其类似物的人类肥胖新治疗方法。目前的研究工作集中在瘦素受体研究以及ob基因多态性及其在包括肥胖和神经性厌食症在内的进食障碍中的表达。ob基因是参与能量平衡的少数基因之一,然而,却是非常有前景的一个。