Decreased Expression of Adrenomedullin during Adipocyte-Differentiation of 3T3-L1 Cells

Li, Yin; Totsune, Kazuhito; Takeda, Kazuhisa; Furuyama, Kazumichi; Shibahara, Shigeki; Takahashi, Kazuhiro

doi:10.1291/hypres.26.s41

Cited by 18 publications

(6 citation statements)

References 30 publications

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“…It has been recently reported that AM mRNA expression in 3T3-L1 cells decreased during preadipocyte differentiation by day 4 (19,20). In contrast, our present study employing longer incubation periods (3-9 days) clearly demonstrated that AM mRNA expression as well as IR-AM secretion decreased to a very low level during the early predifferentiation phase (day 3) but markedly increased during the late phase (days 6 -9).…”

Section: Discussioncontrasting

confidence: 69%

Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues

Fukai

Yoshimoto

Sugiyama

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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.-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 activitymodifying 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 tissuespecific 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. adipocyte; obesity; 3T3-L1 cells

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Section: Discussioncontrasting

confidence: 69%

Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues

Fukai

Yoshimoto

Sugiyama

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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“…However, reported studies of the expression of AM in preadipocytes during differentiation and in adipocytes are limited and inconsistent. Li et al (14) studied the expression of AM and resistin in 3T3-L1 preadipocytes and adipocytes by Northern blot analysis and showed that AM mRNA was expressed in 3T3-L1 preadipocytes but was undetectable in adipocytes, whereas resistin mRNA was not detected in 3T3-L1 preadipocytes but was expressed in adipocytes. It was also reported that preadipocytes at early differentiation stages secreted AM, but mature adipocytes did not secrete AM (34).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies demonstrated that rat adipose tissue contains AM mRNA (14,23), and adipose tissue obtained from rats fed a high-fat diet expresses greater amounts of AM than that obtained from rats fed a normal diet (2). In addition, studies in humans showed that plasma AM correlates with body mass index, and circulating AM is elevated in overweight patients with essential hypertension (34) and is decreased with a reduction of body weight by a hypocaloric diet (18), suggesting a role of AM in human adipose tissue.…”

mentioning

confidence: 99%

Role of adrenomedullin system in lipid metabolism and its signaling mechanism in cultured adipocytes

Iemura-Inaba¹,

Nishikimi²,

Akimoto³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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.-We investigated the levels of adrenomedullin (AM) system during the process of preadipocyte differentiation and its role in lipid metabolism and cellular signaling mechanism in differentiated adipocytes. We cultured rat preadipocytes and measured the following during the process of differentiation: two molecular forms of AM in the culture medium using a specific immunoradiometric assay and gene expression of AM and its receptor component using RT-PCR analysis. In differentiated adipocytes, we measured the effects of AM on the intracellular cAMP level, lipolysis, glucose incorporation, and the protein levels. Two molecular forms of AM were secreted into the medium, and the AM-mature/AM-total ratio was increased after 6 days of differentiation. Cultured rat preadipocytes highly expressed the genes of AM and its receptor components at day 1, and they increased at day 10. Administration of AM to preadipocytes increased the number of Oil Red O-positive adipocytes and spectrophotometric absorbance of Oil Red O. AM dose dependently increased cAMP level and lipolysis, and its effect was blocked by CGRP(8-37). Isoproterenol increased lipolysis, and AM had additive effects on isoproterenol-induced lipolysis. KT5720 and U0126 significantly inhibited the AM-induced lipolysis, whereas KT5720, but not U0126, significantly inhibited the isoproterenol-induced lipolysis. AM increased glucose incorporation and its effect was blocked by wortmannin. Western blot analysis revealed that AM increased phospho PKA, ERK, and Akt. These results indicate that AM and its receptor component are highly expressed in cultured adipocytes and may play a role in lipid metabolism via a different signaling pathway.adipocyte; calcitonin receptor like receptor; receptor activity-modifying proteins; lipolysis ADRENOMEDULLIN (AM) IS A POTENT hypotensive peptide that consists of 52 amino acids with an intramolecular disulfide bond and shares slight homology with calcitonin gene-related peptide (12). AM acts through seven-transmembrane domain G protein-coupled receptor, calcitonin receptor-like receptor (CLR), which associate with the receptor activity-modifying proteins (RAMP) 2 and RAMP 3 (17). AM circulates in human plasma, and the plasma AM concentration is increased in patients with cardiovascular diseases, including hypertension, renal failure, heart failure, and myocardial infarction, in proportion to the severity of the disease (7,19,31). AM messenger RNA is highly expressed in the kidneys, lung, vasculature, and cardiac ventricles (12). AM is considered to act as an autocrine and/or paracrine factor, and increased AM in various pathological conditions exerts cardiorenoprotective effects via antiapoptotic, anti-inflammatory, and antioxidative actions (8,22,28). These facts suggest that AM is involved in the regulation of the cardiovascular system.Recent studies demonstrated that rat adipose tissue contains AM mRNA (14, 23), and adipose tissue obtained from rats fed a high-fat diet expresses greater amounts of AM than that obtained from rats fed ...

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“…However, we (41) previously demonstrated that the kinetics of AM secretion from sWAT preadipocytes undergoing in vitro differentiation was opposite to that of leptin. Also, Li et al (28) showed that AM mRNA was expressed in 3T3-L1 preadipocytes but was undetectable in adipocytes and that AM immunoreactivity was detected in the culture media of 3T3-L1 preadipocytes and adipocytes, with higher concentrations found in preadipocytes. Taken together, the above-mentioned observations suggest that preadipocytes in eWAT can synthesize AM.…”

Section: Discussionmentioning

confidence: 99%

Expression of adrenomedullin in human epicardial adipose tissue: role of coronary status

Silaghi¹,

Achard²,

Paulmyer‐Lacroix³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Epicardial white adipose tissue (eWAT) is in close contact with coronary vessels and therefore could alter coronary homeostasis. Adrenomedullin (AM) is a potent vasodilatator and antioxidative peptide which has been shown to play a cytoprotective role in experimental models of acute myocardial infarction. We studied, using immunohistochemistry and qRT-PCR, the expression of AM and its receptors calcitonin receptor-like receptor (CRLR), and receptor activity-modifying protein (RAMP)2 and -3 in paired biopsies of subcutaneous WAT (sWAT) and eWAT obtained from patients with coronary artery disease (CAD) or without CAD (NCAD). In eWAT obtained from NCAD or CAD patients, immunoreactivity for AM, CRLR, and RAMP2 and -3 was detected in blood vessel walls and isolated stromal cells close to adipocytes. Some of the AM positive stromal cells colocalized CD68 immunoreactivity. eWAT from CAD patients showed increased AM immunoreactivity and AM gene expression. CRLR mRNA levels were comparable in sWAT of both groups and decreased by 40-50% in eWAT, irrespectively of the coronary status. RAMP2 mRNA concentrations did not change while RAMP3 mRNA levels increased in sWAT from CAD patients. There was a positive linear relationship between eWAT 11beta-hydroxysteroid dehydrogenase type 1 mRNA (11beta-HSD-1, the enzyme that converts inactive to active glucocorticoids) and AM mRNA. In conclusion, we demonstrate that AM and its receptors are expressed in eWAT. Our data suggest that eWAT AM, which could originate from macrophages, is related to 11beta-HSD-1 expression. AM synthesis, which is increased in eWAT during chronic CAD in humans, can play a cardioprotective role.

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Decreased Expression of Adrenomedullin during Adipocyte-Differentiation of 3T3-L1 Cells

Abstract: Adrenomedullin (AM) is a potent vasodilator peptide which has an inhibitory action on insulin secretion.Resistin is a novel peptide specifically secreted from adipocytes, and implicated in insulin resistance. We

Cited by 18 publications

References 30 publications

Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues

Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues

Role of adrenomedullin system in lipid metabolism and its signaling mechanism in cultured adipocytes

Expression of adrenomedullin in human epicardial adipose tissue: role of coronary status

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