Reizes Ofer, Benoit Stephen C, Clegg Deborah J
Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, NC10, Cleveland, OH 44195, United States.
Int J Biochem Cell Biol. 2008;40(1):28-45. doi: 10.1016/j.biocel.2007.06.011. Epub 2007 Jun 30.
Body weight is tightly regulated by a feedback mechanism involving peripheral adiposity signals and multiple central nervous system neurotransmitter pathways. Despite the tight regulation of body weight there is an increase in the prevalence of obesity and overweight in Western society. Obesity and overweight are conditions of excess body weight stored as fat. Syndecan-3, a member of the syndecan family of type I transmembrane heparan sulfate proteoglycans is a novel a regulator of feeding behavior and body weight. Syndecans are extracellular matrix molecules (ECMs) that modulate cell adhesion, cell-cell interactions and ligand-receptor interactions. The finding that syndecan-3 can regulate body weight is novel and provides a unique link between the extracellular matrix and body weight regulatory mechanisms. Uniquely, hormones such as leptin previously thought only to regulate body weight by modulating neuropeptide levels, have now been demonstrated to regulate neuronal plasticity in the hypothalamus. ECMs and syndecans have long been recognized as regulators of plasticity. Therefore, this review will focus on highlighting the role of syndecans and in particular syndecan-3 in neuronal development and synaptic organization and how these processes may integrate body weight regulation. As part of this review, we will highlight how syndecan-3 can mediate the activity of adiposity signals, such as leptin, and facilitate changes in neuronal plasticity.
体重通过一种涉及外周脂肪信号和多个中枢神经系统神经递质途径的反馈机制受到严格调节。尽管体重受到严格调控,但西方社会肥胖和超重的患病率仍在上升。肥胖和超重是体内以脂肪形式储存的过多体重的状况。Syndecan-3是I型跨膜硫酸乙酰肝素蛋白聚糖的syndecan家族成员,是一种新型的进食行为和体重调节因子。Syndecans是细胞外基质分子(ECM),可调节细胞粘附、细胞间相互作用和配体-受体相互作用。Syndecan-3能够调节体重这一发现是新颖的,并且在细胞外基质与体重调节机制之间提供了独特的联系。独特的是,诸如瘦素之类的激素以前被认为仅通过调节神经肽水平来调节体重,现在已被证明可调节下丘脑的神经元可塑性。ECM和syndecans长期以来一直被认为是可塑性的调节因子。因此,本综述将重点强调syndecans尤其是syndecan-3在神经元发育和突触组织中的作用,以及这些过程如何整合体重调节。作为本综述的一部分,我们将重点介绍syndecan-3如何介导肥胖信号(如瘦素)的活性,并促进神经元可塑性的变化。