Garruti Gabriella, Giusti Vittorio, Nussberger Jürg, Darimont Christian, Verdumo Chantal, Amstutz Catherine, Puglisi Francesco, Giorgino Francesco, Giorgino Riccardo, Cotecchia Susanna
Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 27, CH-1005 Lausanne, Switzerland.
Obesity (Silver Spring). 2007 Sep;15(9):2181-9. doi: 10.1038/oby.2007.259.
Atrial natriuretic peptide (ANP) is a secretory hormone displaying diuretic, natriuretic, and vasorelaxant activities. Recently, its lipolytic activity has been reported. Since the expression of ANP in adipose tissue has not been documented, we used real-time reverse transcriptase polymerase chain reaction (RT-PCR) to investigate the expression of ANP in human adipose tissue and preadipocytes.
RNA was extracted from the human adipose tissue of severely obese premenopausal women as well as from human preadipocytes. For human preadipocytes, two cell systems were investigated: the human preadipose immortalized (Chub-S7) cells, a well-characterized human preadipose cell line, and primary preadipocytes derived from the stromal vascular fraction of the human adipose tissue. We measured the mRNA of ANP, of corin (a transmembrane serine protease involved in the conversion of pro-ANP to ANP) and of uncoupling protein 2 (UCP2; a control gene known to be ubiquitously expressed). The expression of ANP was also investigated using immunofluorescence and radioimmunoassay in Chub-S7 cells and human primary preadipocytes in culture.
Our results indicate that ANP and corin are expressed at the mRNA level in human adipose tissue and preadipocytes. Immunofluorescence experiments demonstrated that pro-ANP was expressed in Chub-S7 cells. In addition, ANP secretion could be measured in Chub-S7 cells and human primary preadipocytes in culture. Rosiglitazone, a selective peroxisome proliferator-activated receptor type gamma (PPAR-gamma) agonist promoting adipocyte differentiation, was found to modulate both ANP expression and secretion in preadipocytes.
Our findings suggest the existence of an autocrine/paracrine system for ANP in the human adipose tissue whose implications in lipolysis and cardiovascular function need to be further explored.
心房利钠肽(ANP)是一种具有利尿、利钠和血管舒张活性的分泌性激素。最近,其脂解活性也有报道。由于ANP在脂肪组织中的表达尚未见文献记载,我们采用实时逆转录聚合酶链反应(RT-PCR)来研究ANP在人脂肪组织和前脂肪细胞中的表达。
从严重肥胖的绝经前女性的人脂肪组织以及人前脂肪细胞中提取RNA。对于人前脂肪细胞,研究了两种细胞体系:人永生化前脂肪细胞(Chub-S7),一种特征明确的人前脂肪细胞系,以及源自人脂肪组织基质血管部分的原代前脂肪细胞。我们检测了ANP、corin(一种参与前ANP转化为ANP的跨膜丝氨酸蛋白酶)和解偶联蛋白2(UCP2;一个已知在各处均有表达的对照基因)的mRNA。还通过免疫荧光和放射免疫分析法在培养的Chub-S7细胞和人原代前脂肪细胞中研究了ANP的表达。
我们的结果表明,ANP和corin在人脂肪组织和前脂肪细胞的mRNA水平上表达。免疫荧光实验表明,前ANP在Chub-S7细胞中表达。此外,在培养的Chub-S7细胞和人原代前脂肪细胞中可检测到ANP的分泌。罗格列酮,一种促进脂肪细胞分化的选择性过氧化物酶体增殖物激活受体γ(PPAR-γ)激动剂,被发现可调节前脂肪细胞中ANP的表达和分泌。
我们的发现提示人脂肪组织中存在ANP的自分泌/旁分泌系统,其在脂解和心血管功能方面的意义有待进一步探索。