Acta Pharmacologica Sinica 2008 May; 29 (5): 587-592; doi: 10.1111/j.1745-7254.2008.00793.x

Acta Pharmacologica Sinica 2008 May; 29 (5): 587-592; doi: 10.1111/j.1745-7254.2008.00793.x

Original Article

Downregulation of STEAP4, a highly-expressed TNF-α-inducible gene in adipose tissue, is associated with obesity in humans¹

Chun-mei ZHANG^2,3,4, Xia CHI^2,3,4, Bin WANG^2,3, Min ZHANG^2,3, Yu-hui NI^2,3, Rong-hua CHEN³, Xiao-nan LI^2,3,5, Xi-rong GUO^2,3,5

²Department of Pediatrics, Nanjing Maternal and Child Health Hospital of Nanjing Medical University, Nanjing 210004, China; ³Institute of Pediatrics, Nanjing Medical University, Nanjing 210029, China

Aim: To determine the relationship between six-transmembrane epithelial antigen of the prostate 4 (STEAP4) expression and obesity.

Methods: RT_PCR and immunoblot analyses were performed to determine the differential expressions of STEAP4 mRNA and protein, respectively, in human omental adipose tissue from obese patients and normal weight controls. The expression pattern of STEAP4 mRNA in various human tissues was determined by RT_PCR. The subcellular localization of the STEAP4 protein in human adipose tissue was confirmed by immunohistochemistry. Finally, we confirmed that cultured human omental adipose tissue undergoes TNF-α-mediated regulation of the STEAP4 expression.

Results: STEAP4 mRNA and protein levels were downregulated in omental adipose tissue from obese patients relative to normal controls. The STEAP4 expression was most abundant in human adipose tissue. An immunohistochemical analysis confirmed that STEAP4 was associated with the plasma membrane of adipocytes. The STEAP4 expression was induced by TNF-α in a dose-dependent manner in human adipose tissue.

Conclusion: STEAP4 was abundantly expressed in human adipose tissue, and the STEAP4 expression was significantly downregulated in obese patients. STEAP4 localized to the plasma membrane of adipocytes, and the STEAP4 expression was induced by TNF-α in adipose tissue. These data suggest that STEAP4 may play a significant role in the development of human obesity.

Keywords: six-transmembrane epithelial antigen of the prostate 4; obesity; tumor necrosis factor-a; adipose tissuess

¹Project supported by grants from the National Natural Science Foundation of China (No 30772364), the Natural Science Foundation of Jiangsu Province, China (No BK2007230), the Foundation of Ministry of Education, China (No 20070312001), and Nanjing Medical University (No 07NMUZ024).

⁴These authors contributed equally to this work.
⁵Correspondence to Dr Xi-rong GUO and Dr Xiao-nan LI.
Phn 86-25-8686-2996.
E-mail xrguo@njmu.edu.cn (Xi-rong GUO)
Phn 86-25-8686-2996.
E-mail xnli@njmu.edu.cn (Xiao-nan LI)
Received 2007-11-20 Accepted 2008-02-25

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