Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 11, SE-405 30, Göteborg, Sweden.
Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 11, SE-405 30, Göteborg, Sweden.
Biochem Biophys Res Commun. 2021 Jan 1;534:707-713. doi: 10.1016/j.bbrc.2020.11.013. Epub 2020 Nov 28.
In the current work we have investigated the cellular and molecular regulation of resistin secretion in cultured and primary mouse adipocytes. Resistin is an adipose tissue hormone proposed to contribute to metabolic disease. In rodents, resistin is secreted from white adipocytes whereas it is in humans synthesised and released from other cell types within white adipose tissue. The metabolic importance of resistin has been studied in both mouse and man, but the regulation of its release remains poorly investigated. Here we define that, in mouse adipocytes, resistin secretion is triggered by an intracellular elevation of cAMP and/or Ca. Resistin release is stimulated via activation of beta 3 adrenergic receptors (βARs) and the downstream signalling protein exchange protein activated by cAMP (Epac). The secretion of resistin is markedly abrogated in adipocytes isolated from obese and diabetic mice. Immunocytochemical staining demonstrates a significant overlap between signals for resistin and the adipocyte hormone adiponectin. Our data propose that resistin and adiponectin are contained within the same vesicles in mouse adipocytes and that the two hormones are co-secreted in response to the same exocytosis-triggering signals.
在当前的工作中,我们研究了培养的和原代的小鼠脂肪细胞中抵抗素分泌的细胞和分子调节。抵抗素是一种脂肪组织激素,被认为与代谢疾病有关。在啮齿动物中,抵抗素由白色脂肪细胞分泌,而在人类中,它由白色脂肪组织内的其他细胞类型合成和释放。抵抗素的代谢重要性在小鼠和人类中都得到了研究,但它的释放调节仍未得到充分研究。在这里,我们定义了在小鼠脂肪细胞中,抵抗素的分泌是由细胞内 cAMP 和/或 Ca 的升高触发的。抵抗素的释放通过激活β3 肾上腺素能受体 (βAR) 和下游信号蛋白 cAMP 激活的交换蛋白 (Epac) 来刺激。从肥胖和糖尿病小鼠中分离的脂肪细胞中,抵抗素的分泌明显被阻断。免疫细胞化学染色表明抵抗素和脂肪激素脂联素的信号有显著重叠。我们的数据表明,抵抗素和脂联素在小鼠脂肪细胞中存在于相同的囊泡中,并且这两种激素在响应相同的胞吐触发信号时被共同分泌。