da Silva Inês V, Soveral Graça
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
Department Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
Adv Exp Med Biol. 2023;1398:289-302. doi: 10.1007/978-981-19-7415-1_20.
Obesity is one of the most important metabolic disorders of this century and is associated with a cluster of the most dangerous cardiovascular disease risk factors, such as insulin resistance and diabetes, dyslipidemia, and hypertension, collectively named Metabolic Syndrome. The role of aquaporins (AQP) in glycerol metabolism facilitating glycerol release from the adipose tissue and distribution to various tissues and organs unveils these membrane channels as important players in lipid balance and energy homeostasis and points to their involvement in a variety of pathophysiological mechanisms including insulin resistance, obesity, and diabetes. This review summarizes the physiologic role of aquaglyceroporins in glycerol metabolism and lipid homeostasis, describing their specific tissue distribution, involvement in glycerol balance, and implication in obesity and fat-related metabolic complications. The development of specify pharmacologic modulators able to regulate aquaglyceroporins expression and function, in particular AQP7 in adipose tissue, might constitute a novel approach for controlling obesity and other metabolic disorders.
肥胖是本世纪最重要的代谢紊乱之一,与一系列最危险的心血管疾病风险因素相关,如胰岛素抵抗和糖尿病、血脂异常以及高血压,这些统称为代谢综合征。水通道蛋白(AQP)在甘油代谢中发挥作用,促进甘油从脂肪组织释放并分布到各个组织和器官,这揭示了这些膜通道在脂质平衡和能量稳态中是重要参与者,并表明它们参与了包括胰岛素抵抗、肥胖和糖尿病在内的多种病理生理机制。这篇综述总结了水甘油通道蛋白在甘油代谢和脂质稳态中的生理作用,描述了它们在特定组织中的分布、对甘油平衡的影响以及在肥胖和脂肪相关代谢并发症中的作用。开发能够调节水甘油通道蛋白表达和功能(特别是脂肪组织中的AQP7)的特异性药理调节剂,可能构成控制肥胖和其他代谢紊乱的新方法。