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Comment on: Harmancey et al. (2007) Adrenomedullin Inhibits Adipogenesis Under Transcriptional Control of Insulin: Diabetes 56:553–563

From the Department of Analytical Medical Technology, Tohoku University School of Health Sciences, Sendai, Japan

Address correspondence to Kazuhiro Takahashi, MD, PhD, Department of Analytical Medical Technology, Tohoku University School of Health Sciences, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan. E-mail: ktaka-md{at}mail.tains.tohoku.ac.jp

I have read with great interest the article by Harmancey et al. (1) on inhibition of adipogenesis by adrenomedullin. Previous studies, including ours (2–4), have shown that adrenomedullin is produced and secreted by adipocytes and adipose tissues, whereas the reported effects of adrenomedullin on lipolysis are conflicting (5,6). Harmancey et al. (1) have clearly shown inhibition of adipogenesis by adrenomedullin using small interfering RNA technology. However, I have several concerns regarding this article. First, the concentration of exogenously added adrenomedullin (100 nmol/l) was very high in the experiment on the inhibitory effects on adipogenesis (Fig. 1 in article). The adrenomedullin concentrations in the medium of cultured adipocytes rarely exceed 1 nmol/l (2,4). Second, the authors used 3T3-F442A preadipocytes but not adipocytes in the transfection study (Fig. 6 in article). There is a considerable difference in the adrenomedullin promoter activity between preadipocytes and adipocytes, probably due to the presence of another promoter sequence in the adrenomedullin gene named ADRE-AR, as shown in our previous study using 3T3-L1 cells (3). Third, the authors placed too much emphasis on the inhibition of adrenomedullin expression by insulin in adipocytes. Adrenomedullin expression was rather increased, however, during adipocyte differentiation of human mesenchymal stem cells, which was induced by the medium containing insulin (4). Finally, the authors showed a high negative correlation between plasma adrenomedullin and insulin levels in 10 obese subjects. (Table 1 in the article shows seven male and six female subjects.) Plasma insulin levels in these obese subjects were not elevated, however, when compared with 10 lean subjects. (Table 1 in the article shows six male and seven female subjects.) If the authors had included obese subjects with increased plasma insulin levels in this analysis, the results may have been different. I agree with the inhibitory effect of adrenomedullin on adipogenesis shown by the small interfering RNA technology but cannot agree with the proposed manner of the insulin involvement in this phenomenon.

REFERENCES

1. Harmancey R, Senard JM, Rouet P, Pathak A, Smih F: Adrenomedullin inhibits adipogenesis under transcriptional control of insulin. Diabetes 56:553–563, 2007[Abstract/Free Full Text]
2. Li Y, Totsune K, Takeda K, Furuyama K, Shibahara S, Takahashi K: Differential expression of adrenomedullin and resistin in 3T3-L1 adipocytes treated with tumor necrosis factor-alpha. Eur J Endocrinol 149:231–238, 2003[Abstract]
3. Li Y, Zhang Y, Furuyama K, Yokoyama S, Takeda K, Shibahara S, Takahashi K: Identification of adipocyte differentiation-related regulatory element for adrenomedullin gene repression (ADRE-AR) in 3T3-L1 cells. Peptides 27:1405–1414, 2006[Medline]
4. Li Y, Zhang Y, Shibahara S, Takahashi K: Adrenomedullin in adipocyte differentiation of human mesenchymal stem cells. Biochem Biophys Res Commun 350:616–622, 2006[Medline]
5. Harmancey R, Senard JM, Pathak A, Desmoulin F, Claparols C, Rouet P, Smih F: The vasoactive peptide adrenomedullin is secreted by adipocytes and inhibits lipolysis through NO-mediated beta-adrenergic agonist oxidation. FASEB J 19:1045–1047, 2005[Abstract/Free Full Text]
6. Linscheid P, Seboek D, Zulewski H, Keller U, Muller B: Autocrine/paracrine role of inflammation-mediated calcitonin gene-related peptide and adrenomedullin expression in human adipose tissue. Endocrinology 146:2699–2708, 2005[Abstract/Free Full Text]

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This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Takahashi, K. Search for Related Content PubMed PubMed Citation Articles by Takahashi, K. Social Bookmarking                What's this?