Abstract：
Glucocorticoids (GCs) play an important role in metabolic adaptation, regulating carbohydrate-lipid homeostasis and the immune system. Because they also have anti-inflammatory and immunosuppressive properties, synthetic analogues of GCs have been developed and are widely used in the treatment of chronic inflammatory conditions and in organ transplantation. GCs are among the most commonly prescribed drugs in the world. However, long term and high GC doses can cause side effects such as GC-induced diabetes and lipodystrophy. In recent years, a large number of independent studies have reported the effects of constitutive and adipocyte-specific deletion of the GC receptor (GR) in mice under different diets and treatments, resulting in contrasting phenotypes. To avoid potential compensatory mechanisms associated with the constitutive adipocyte GR silencing during adipose tissue development, our team has generated an inducible mouse model of GR deletion specifically in the adipocyte (AdipoGR-KO). Using this mouse model, we were able to demonstrate the critical role of the adipocyte GR in GC-induced metabolic changes. Indeed, under conditions of hypercorticism, AdipoGR-KO mice showed an improvement in glucose tolerance and insulin sensitivity, as well as in lipid profile, despite a massive increase in adiposity. This result is explained by a densification of adipose tissue vascularization, highlighting the repressive role of adipocyte GR in the healthy expansion of this tissue. Our work has largely contributed to the demonstration of the important role of the adipocyte GR in the physiology and pathophysiology of the adipose tissue and its impact on energy homeostasis.
摘要：
糖皮质激素(GCs)在代谢适应中起重要作用,调节碳水化合物-脂质稳态和免疫系统。因为它们还具有抗炎和免疫抑制特性，已经开发了GC的合成类似物,并广泛用于治疗慢性炎症和器官移植。GCs是世界上最常用的处方药之一。然而,长期和高GC剂量可引起副作用，如GC诱导的糖尿病和脂肪代谢障碍。近年来,大量独立的研究报道了GC受体（GR）的组成型和脂肪细胞特异性缺失在不同饮食和治疗下的小鼠中的作用，导致不同的表型。为了避免脂肪组织发育过程中与组成型脂肪细胞GR沉默相关的潜在代偿机制，我们的团队已经建立了一个可诱导的小鼠模型，特别是在脂肪细胞中的GR缺失（AdipoGR-KO）。使用这个鼠标模型，我们能够证明脂肪细胞GR在GC诱导的代谢变化中的关键作用。的确,在高皮质的条件下，AdipoGR-KO小鼠表现出葡萄糖耐量和胰岛素敏感性的改善，以及在脂质分布中，尽管肥胖人数大幅增加。这一结果可以解释为脂肪组织血管化的致密化，强调脂肪细胞GR在该组织健康扩张中的抑制作用。我们的工作在很大程度上证明了脂肪细胞GR在脂肪组织的生理和病理生理学中的重要作用及其对能量稳态的影响。
