Cellular reprogramming into a brown adipose tissue-like phenotype by co-expression of HB-EGF and ADAM 12S

• Published in: Growth factors (Chur, Switzerland) Switzerland), 2013-12, Vol.31 (6), p.185-198
• Main Authors: Zhou, Z., Darwal, M. A., Cheng, E. A., Taylor, S. R., Duan, E., Harding, P. A.
• Format: Article
• Language: English
• Subjects: ADAM 12S; adipogenesis; brown fat; HB-EGF; white fat
• ISSN: 0897-7194; 1029-2292
• DOI: 10.3109/08977194.2013.840297

Abstract Abnormal adipogenesis leads to excessive fat accumulation and several health disorders. Mouse fibroblasts (MLC) transfected with ADAM 12S and HB-EGF promoted lipid accumulation. Addition of KBR-7785, an ADAM 12S inhibitor, to HB-EGF/ADAM 12S expressing cells suppressed adipogenesis. BrdU incorporation was attenuated and enhanced mitotracker staining was observed in HB-EGF/ADAM 12S cells. Quantitative real time RT-PCR resulted in elevated levels of expression of three brown adipose tissue (BAT) genes (PRDM16, PGC-1α, and UCP-1), while expression levels of the three white adipose tissue (WAT) genes (PPARγ, C/EBPα, and AKT-1) were unaltered in HB-EGF/ADAM 12S cells. Amino- or carboxy-terminal deletions of HB-EGF (HB-EGFΔN and HB-EGFΔC) co-expressed with ADAM 12S stimulated lipid accumulation. Human epidermoid carcinoma cells (A431) also exhibited lipid accumulation by HB-EGF/ADAM 12S co-expression. These studies suggest ADAM 12S and HB-EGF are involved in cellular plasticity resulting in the production of BAT-like cells and offers insight into novel therapeutic approaches for fighting obesity.