Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 11, SE-405 30, Göteborg, Sweden.
Sci Rep. 2019 Jul 23;9(1):10680. doi: 10.1038/s41598-019-47113-8.
The hormone adiponectin is secreted by white adipocytes and has been put forward as a key mediator of obesity-linked insulin resistance and the metabolic syndrome. Although adiponectin was discovered two decades ago, the knowledge about the molecular and cellular regulation of its secretion is incomplete. Here we have investigated the adrenergic regulation of adiponectin secretion in primary visceral (gonadal) adipocytes isolated from lean or obese/diabetic mice. We show that visceral adipocyte adiponectin release is triggered by cAMP/catecholamines via signalling pathways involving adrenergic beta-3-receptors (βARs) and Exchange Protein directly Activated by cAMP, isoform 1 (Epac1). The adrenergically stimulated adiponectin secretion is blunted in visceral adipocytes isolated from obese and diabetic mice and our results suggest the existence of a secretory defect. We have previously shown that adiponectin secretion in subcutaneous adipocytes is abolished in the obese/diabetic state due to reduced abundance of βARs and Epac1. However, here we show that protein levels of βARs and Epac1 are maintained in visceral adipocytes from obese/diabetic mice proposing that other molecular defects underlie the blunted adiponectin release. Gene expression analysis indicate diabesity-associated disturbances of the signalling downstream of Epac1 and/or the exocytotic process itself. Our study proposes that visceral adipocytes partake in the regulated secretion of adiponectin and may thus influence circulating levels of the hormone, in health and in metabolic disease.
脂联素是由白色脂肪细胞分泌的激素，被提出作为肥胖相关胰岛素抵抗和代谢综合征的关键介质。尽管脂联素在二十年前就被发现了，但关于其分泌的分子和细胞调节的知识还不完全。在这里，我们研究了从瘦鼠或肥胖/糖尿病鼠分离的原代内脏（性腺）脂肪细胞中肾上腺素能对脂联素分泌的调节作用。我们表明，内脏脂肪细胞脂联素的释放是由 cAMP/儿茶酚胺通过涉及肾上腺素能β3-受体（βAR）和 cAMP 直接激活的交换蛋白 1（Epac1）的信号通路触发的。从肥胖和糖尿病小鼠分离的内脏脂肪细胞中，肾上腺素能刺激的脂联素分泌减弱，我们的结果表明存在分泌缺陷。我们之前已经表明，由于βAR 和 Epac1 的丰度降低，肥胖/糖尿病状态下的皮下脂肪细胞中脂联素的分泌被消除。然而，在这里我们表明，肥胖/糖尿病小鼠的内脏脂肪细胞中βAR 和 Epac1 的蛋白水平保持不变，这表明其他分子缺陷是脂联素释放减弱的基础。基因表达分析表明，Epac1 下游的信号和/或胞吐过程本身与糖尿病相关的信号紊乱有关。我们的研究表明，内脏脂肪细胞参与脂联素的调节分泌，因此可能会影响激素在健康和代谢疾病中的循环水平。
