Strader April D, Reizes Ofer, Woods Stephen C, Benoit Stephen C, Seeley Randy J
Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio 45237, USA.
J Clin Invest. 2004 Nov;114(9):1354-60. doi: 10.1172/JCI20631.
The accurate matching of caloric intake to caloric expenditure involves a complex system of peripheral signals and numerous CNS neurotransmitter systems. Syndecans are a family of membrane-bound heparan sulfate proteoglycans that modulate ligand-receptor interactions. Syndecan-3 is heavily expressed in several areas of the brain, including hypothalamic nuclei, which are known to regulate energy balance. In particular, syndecans have been implicated in modulation of the activity of the melanocortin system, which potently regulates energy intake, energy expenditure, and peripheral glucose metabolism. Our data demonstrate that syndecan-3-null mice have reduced adipose content compared with wild-type mice. On a high-fat diet, syndecan-3-null male and female mice exhibited a partial resistance to obesity due to reduced food intake in males and increased energy expenditure in females relative to that of wild-type mice. As a result, syndecan-3-null mice on a high-fat diet accumulated less adipose mass and showed improved glucose tolerance compared with wild-type controls. The data implicate syndecan-3 in the regulation of body weight and suggest that inhibition of syndecan-3 may provide a therapeutic approach for the treatment of obesity resulting from exposure to high-fat diets.
热量摄入与热量消耗的精确匹配涉及一个由外周信号和众多中枢神经系统神经递质系统组成的复杂系统。Syndecans是一类膜结合硫酸乙酰肝素蛋白聚糖家族，可调节配体-受体相互作用。Syndecan-3在大脑的几个区域大量表达，包括已知可调节能量平衡的下丘脑核。特别是，Syndecans参与了黑皮质素系统活性的调节，该系统有力地调节能量摄入、能量消耗和外周葡萄糖代谢。我们的数据表明，与野生型小鼠相比，Syndecan-3基因敲除小鼠的脂肪含量降低。在高脂饮食条件下，Syndecan-3基因敲除的雄性和雌性小鼠相对于野生型小鼠，由于雄性食物摄入量减少和雌性能量消耗增加，表现出对肥胖的部分抗性。因此，与野生型对照相比，高脂饮食的Syndecan-3基因敲除小鼠积累的脂肪量更少，葡萄糖耐量也有所改善。这些数据表明Syndecan-3参与体重调节，并表明抑制Syndecan-3可能为治疗因高脂饮食导致的肥胖提供一种治疗方法。
