Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues
Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues
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DOI：
10.1152/ajpendo.00586.2003
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发表时间：
2005-01-01
影响因子：
5.1
通讯作者：
Hirata, Y
中科院分区：
文献类型：
--
作者：
Fukai, N;Yoshimoto, T;Hirata, Y
肾上腺髓质素（Adrenomedullin，AM）是由多种细胞表达和分泌的，以自分泌/旁分泌的方式发挥多能性作用。本研究旨在探讨AM及其受体基因在脂肪组织中的表达及其在肥胖形成过程中的变化，以及前脂肪细胞的分化过程。成熟脂肪细胞和构成脂肪组织的基质血管细胞均表达AM转录本。AM及其受体成分[降钙素受体样受体和受体活性修饰蛋白-2（CRLR/RAMP 2）] mRNA在多种大鼠脂肪组织中表达，包括附睾、肠系膜、腹膜后和皮下脂肪组织。大鼠和人附睾脂肪组织中AM mRNA水平约为肾脏中AM mRNA水平的十分之一。高脂饮食4 wk大鼠附睾、肠系膜和腹膜后脂肪组织中AM和CRLR/RAMP 2的稳态mRNA水平远高于正常饮食伴血浆AM水平升高的大鼠，而其他器官（如肾脏和肝脏）中的稳态AM mRNA水平则相反下降。在小鼠前脂肪细胞系（3 T3-L1）中，AM mRNA表达在前脂肪细胞分化过程中第3天短暂下降，第6天恢复到基础水平，然后在第9天增加，这抑制了细胞的AM分泌。然而，加入外源性AM或AM受体拮抗剂降钙素基因相关肽-（8 - 37）来阻断内源性AM并不影响前脂肪细胞分化过程中脂滴的积累。本研究首次表明，AM及其受体成分（CRLR/RAMP 2）mRNA在各种脂肪组织中同时表达，其组织特异性上调在肥胖症的发展过程中诱导。这些数据表明，AM可能作为脂肪因子的一个新成员，虽然它的功能作用，以及其在肥胖的病理生理意义，仍有待确定。
Adrenomedullin ( AM) expressed by and secreted from a variety of cells plays pluripotent roles in an autocrine/paracrine fashion. The present study was undertaken to explore the expression of AM and its receptor genes in adipose tissues, their changes during the development of obesity, and the process of preadipocyte differentiation. Both mature adipocytes and stromal vascular cells constituting adipose tissue expressed AM transcript. AM and its receptor component [ calcitonin receptor-like receptor and receptor activity-modifying protein-2 (CRLR/RAMP2)] mRNAs were expressed in a variety of rat adipose tissues, including epididymal, mesenteric, retroperitoneal, and subcutaneous adipose tissue. AM mRNA levels in rat and human epididymal adipose tissue were about one-tenth of those in the kidney. Steady-state mRNA levels of AM and CRLR/ RAMP2 in epididymal, mesenteric, and retroperitoneal adipose tissues in rats fed a high-fat diet for 4 wk were far greater than those in rats with normal diet accompanied by increased plasma AM levels, whereas steady-state AM mRNA levels conversely decreased in other organs, such as kidney and liver. AM mRNA expressed in a mouse preadipocyte cell line (3T3-L1) transiently decreased by day 3, returned to basal level by day 6, and then increased by day 9 during preadipocyte differentiation, which paralleled AM secretion from the cells. However, the addition of either exogenous AM or AM receptor antagonist calcitonin gene-related peptide-(8 - 37), to block endogenous AM did not affect lipid droplet accumulation during preadipocyte differentiation. The present study demonstrates for the first time that AM and its receptor component ( CRLR/ RAMP2) mRNAs were concomitantly expressed in various adipose tissues, whose tissue-specific upregulation was induced during the development of obesity. These data suggest that AM may act as a new member of adipokines, although its functional role, as well as its pathophysiological significance in obesity, remains to be determined.