Majdic Gregor
Center for Animal Genomics, Veterinary Faculty, University of Ljubljana.
Acta Chim Slov. 2009 Jan 1;56(2):289-296.
Body weight regulation is one of the most important homeostatic mechanisms. In recent years many molecular players involved in the energy balance were identified. Although the discovery of leptin almost 15 years ago sparked a great enthusiasm that we will soon understand molecular pathways regulating body weight homeostasis, these expectations turned out to be premature. We know that main site of body weight homeostasis is the hypothalamus with four primary regions - arcuate, paraventricular and ventromedial nuclei, and lateral hypothalamus. Downstream from leptin, the most important signalling peptides are melanocortin, CART, neuropeptide Y and AgRP. Beside those, many other signalling pathways that include signalling by adipokines such as resistin and adiponectin, endocannabinoids in hypothalamus, glucocorticoids from adrenal glands, sex steroid hormones from the gonads and several peptides/hormones secreted by gastrointestinal tract are involved in the body weight homeostasis, and the real challenge for the future is how to understand the complicated interplay between all these molecules. This seems to be a daunting task, but with the new discoveries and with the use of the new molecular tools a rapid progress is being made. The real challenge for the future nevertheless remains how to interfere with these processes and how to help people with body weight problems that are not caused simply by sedentary life style, but also by the genetic make-up of these individuals.
体重调节是最重要的稳态机制之一。近年来，许多参与能量平衡的分子因子被识别出来。尽管大约15年前瘦素的发现引发了人们极大的热情，认为我们很快就能理解调节体重稳态的分子途径，但这些期望后来被证明为时过早。我们知道体重稳态的主要部位是下丘脑，它有四个主要区域——弓状核、室旁核、腹内侧核和外侧下丘脑。在瘦素的下游，最重要的信号肽是促黑素、可卡因-安非他明调节转录肽、神经肽Y和AgRP。除此之外，许多其他信号通路也参与体重稳态，包括抵抗素和脂联素等脂肪因子的信号传导、下丘脑内的内源性大麻素、肾上腺分泌的糖皮质激素、性腺分泌的性甾体激素以及胃肠道分泌的几种肽/激素，而未来真正的挑战是如何理解所有这些分子之间复杂的相互作用。这似乎是一项艰巨的任务，但随着新发现以及新分子工具的使用，正在取得快速进展。然而，未来真正的挑战仍然是如何干预这些过程，以及如何帮助那些体重问题不仅仅是由久坐的生活方式引起，还由个体基因组成导致的人。
