Fukai Nozomi, Yoshimoto Takanobu, Sugiyama Toru, Ozawa Naoko, Sato Ryuji, Shichiri Masayoshi, Hirata Yukio
Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8513, Japan.
Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E56-62. doi: 10.1152/ajpendo.00586.2003. Epub 2004 Aug 17.
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.
由多种细胞表达并分泌的肾上腺髓质素（AM）以自分泌/旁分泌方式发挥多种作用。本研究旨在探讨AM及其受体基因在脂肪组织中的表达、肥胖发生过程中的变化以及前脂肪细胞分化过程。构成脂肪组织的成熟脂肪细胞和基质血管细胞均表达AM转录本。AM及其受体组分[降钙素受体样受体和受体活性修饰蛋白-2（CRLR/RAMP2）]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。大鼠和人类附睾脂肪组织中AM mRNA水平约为肾脏中的十分之一。高脂饮食喂养4周的大鼠附睾、肠系膜和腹膜后脂肪组织中AM和CRLR/RAMP2的稳态mRNA水平远高于正常饮食大鼠，同时血浆AM水平升高，而肾脏和肝脏等其他器官中的稳态AM mRNA水平则相反降低。在小鼠前脂肪细胞系（3T3-L1）中，AM mRNA在分化第3天短暂下降，第6天恢复至基础水平，然后在第9天升高，这与细胞分泌AM的情况平行。然而，添加外源性AM或AM受体拮抗剂降钙素基因相关肽-（8-37）以阻断内源性AM并不影响前脂肪细胞分化过程中的脂滴积累。本研究首次证明AM及其受体组分（CRLR/RAMP2）mRNA在各种脂肪组织中同时表达，其组织特异性上调在肥胖发生过程中被诱导。这些数据表明AM可能作为脂肪因子的新成员，尽管其在肥胖中的功能作用及其病理生理意义仍有待确定。
