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1 Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: tyoshimoto.cme{at}tmd.ac.jp.
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 components (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 its receptor components (CRLR/RAMP2) in epididymal, mesenteric, and retroperitoneal adipose tissues in rats fed with high fat diet for 4 weeks 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 mouse preadipocyte cell line (3T3L1) transiently decreased by day 3, returned to basal level by day 6, and then increased by day 9 during preadipocyte differentiation, which paralleled to AM secretion from the cells. However, the addition of either exogenous AM or AM receptor antagonist, CGRP(8-37), to block endogenous AM did not affect lipid droplets accumulation during preadipocyte differentiation. The present study demonstrates for the first time that AM and its receptor components (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.
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