Napolitano A, Lowell B B, Flier J S
Charles A. Dana Research Institute, Boston, MA.
Int J Obes. 1991 Mar;15(3):227-35.
Adipsin gene expression is severely diminished in certain forms of genetic and acquired rodent obesity. Common to many of these models of obesity is decreased sympathetic nervous system (SNS) activity. In addition, treatment of MSG obese mice with the sympathomimetic drug mixture ephedrine and caffeine restores adipsin deficiency to normal, while reversing obesity. Based on these observations, we hypothesized that adipsin gene expression might be regulated through changes in SNS activity with deficient adipsin gene expression in obesity being the result of impaired SNS activity. In the present study we used three models to assess the role of the SNS in regulating adipsin gene expression. First we exposed mice to the cold (4 degrees C), a potent activator of SNS activity. Second, we chemically sympathectomized mice with 60H-dopamine. Third, we treated mice with BRL 26830A, an atypical beta adrenoreceptor agonist. In contrast to our initial hypothesis, these studies demonstrate that alterations of SNS activity do not affect adipsin gene expression in normal mice. Neither increased SNS activity secondary to cold exposure nor decreased SNS activity resulting from sympathectomy alter serum adipsin concentration or adipsin mRNA levels in white (WAT) and brown adipose tissue (BAT). Surprisingly, treatment of lean mice with BRL 26830A decreases both adipsin serum concentrations and adipsin mRNA levels, suggesting a potential role for atypical beta adrenoreceptors in pathways that suppress adipsin expression in vivo. The significance of this observation with respect to adipocyte physiology is unclear at present. Future studies will be aimed at defining the molecular mechanisms by which BRL 26830A suppresses adipsin gene expression and the physiological significance of this effect.
在某些遗传性和后天性啮齿动物肥胖模型中，脂肪酶基因表达严重降低。许多这类肥胖模型的共同特点是交感神经系统（SNS）活性降低。此外，用拟交感神经药物混合物麻黄碱和咖啡因治疗味精肥胖小鼠可使脂肪酶缺乏恢复正常，同时逆转肥胖。基于这些观察结果，我们推测脂肪酶基因表达可能通过交感神经系统活性的变化来调节，肥胖时脂肪酶基因表达不足是交感神经系统活性受损的结果。在本研究中，我们使用了三种模型来评估交感神经系统在调节脂肪酶基因表达中的作用。首先，我们将小鼠暴露于寒冷环境（4摄氏度），这是一种强效的交感神经系统活性激活剂。其次，我们用6-羟多巴胺对小鼠进行化学去交感神经处理。第三，我们用非典型β肾上腺素能受体激动剂BRL 26830A治疗小鼠。与我们最初的假设相反，这些研究表明，交感神经系统活性的改变不会影响正常小鼠的脂肪酶基因表达。无论是寒冷暴露引起的交感神经系统活性增加，还是去交感神经处理导致的交感神经系统活性降低，都不会改变白色（WAT）和棕色脂肪组织（BAT）中的血清脂肪酶浓度或脂肪酶mRNA水平。令人惊讶的是，用BRL 26830A治疗瘦小鼠会降低脂肪酶血清浓度和脂肪酶mRNA水平，这表明非典型β肾上腺素能受体在体内抑制脂肪酶表达的途径中可能发挥作用。目前，这一观察结果对脂肪细胞生理学的意义尚不清楚。未来的研究将旨在确定BRL 26830A抑制脂肪酶基因表达的分子机制以及这种作用的生理意义。
