OR15-3 Expression of BMP8b, a Novel Regulator and Biomarker of Brown Adipose Tissue, is Regulated by Estrogens

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR15-Adipokine Action
Basic/Clinical
Sunday, June 16, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 11:45 AM
Room 303 (Moscone Center)
Aldo Grefhorst*, Johanna C. van den Beukel, E. Leonie A.F van Houten, Jacobie Steenbergen, Piet Kramer, Wilfred F.J. van Ijcken, Jenny A. Visser and Axel PN Themmen
Erasmus MC, Rotterdam, Netherlands
Mammals have two distinct types of adipose tissue. White adipose tissue which stores fat and brown adipose tissue (BAT) which dissipates fat to produce heat. Therefore, BAT activation is considered beneficial in combating obesity. Human and animal studies showed that females have more active BAT. We aimed to find secreted proteins that are predominantly expressed in activated BAT to find BAT biomarkers. In addition, we determined the sex-specificity of these factors.

Microarrays were performed on BAT from adult male mice exposed 24 hours to 23 °C or 4 °C to activate BAT. A top list of cold-induced genes encoding for secreted proteins was screened for BAT specificity. Next, mRNA expression of the BAT-specific genes was studied in BAT of male and female gonadodectomized mice that were exposed to 23 or 4 °C for 24 hours. To study the role of sex steroids in the regulation of BAT-specific genes, we treated male and female mice with diethylstilbestrol (DES) or dihydrotestosterone (DHT), respectively.

Cold exposure enhanced BAT expression of 30 genes encoding extracellular proteins. Top genes were those encoding for ADAMTS1, BMP8b, CTGF, CXCL14, FGF1, FGF9, FGF21, and IGFBP3. From these genes, only Bmp8b, Fgf9 and Fgf21 showed BAT-specific upregulation upon cold exposure. Fgf9 and Fgf21 mRNA expression did not differ between male and female mice but Bmp8b mRNA expression was ~6-fold higher in females than in males. Castration did not affect Bmp8b mRNA expression, whereas ovariectomy severely reduced Bmp8b mRNA expression. Cold exposure elevated Bmp8b mRNA expression in both sexes, independently of the absence or presence of gonads. DES-treated male mice had a ~6-fold induced Bmp8b mRNA expression while DHT almost abolished Bmp8b mRNA expression in female BAT.

In conclusion, BMP8b is a marker of BAT activity. The increased Bmp8b mRNA expression in female mice and upregulation by estrogens suggest that BMP8b plays a role in the increased BAT activity in females.

Nothing to Disclose: AG, JCV, ELAFV, JS, PK, WFJV, JAV, APT

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