title: Dual-specificity phosphatase 10 controls brown adipocyte differentiation by modulating the phosphorylation of p38 mitogen-activated protein kinase.
abstract: BACKGROUND
  Brown adipocytes play an important role in regulating the balance of energy, and as such, there is a strong correlation between obesity and the amount of brown adipose tissue. Although the molecular mechanism underlying white adipocyte differentiation has been well characterized, brown adipocyte differentiation has not been studied extensively. Here, we investigate the potential role of dual-specificity phosphatase 10 (DUSP10) in brown adipocyte differentiation using primary brown preadipocytes.
  
  
  RESULTS
  The expression of DUSP10 increased continuously after the brown adipocyte differentiation of mouse primary brown preadipocytes, whereas the phosphorylation of p38 was significantly upregulated at an early stage of differentiation followed by steep downregulation. The overexpression of DUSP10 induced a decrease in the level of p38 phosphorylation, resulting in lower lipid accumulation than that in cells overexpressing the inactive mutant DUSP10. The expression levels of several brown adipocyte markers such as PGC-1α, UCP1, and PRDM16 were also significantly reduced upon the ectopic expression of DUSP10. Furthermore, decreased mitochondrial DNA content was detected in cells expressing DUSP10. The results obtained upon treatment with the p38 inhibitor, SB203580, clearly indicated that the phosphorylation of p38 at an early stage is important in brown adipocyte differentiation. The effect of the p38 inhibitor was partially recovered by DUSP10 knockdown using RNAi.
  
  
  CONCLUSIONS
  These results suggest that p38 phosphorylation is controlled by DUSP10 expression. Furthermore, p38 phosphorylation at an early stage is critical in brown adipocyte differentiation. Thus, the regulation of DUSP10 activity affects the efficiency of brown adipogenesis. Consequently, DUSP10 can be used as a novel target protein for the regulation of obesity.
authors: Research Center for Integrated Cellulomics, KRIBB, Daejeon, Republic of Korea.
authors: Hye-Ryung
authors: HR
authors: Choi
authors: Won Kon
authors: WK
authors: Kim
authors: Eun Young
authors: EY
authors: Kim
authors: Baek Soo
authors: BS
authors: Han
authors: Jeong-Ki
authors: JK
authors: Min
authors: Seung-Wook
authors: SW
authors: Chi
authors: Sung Goo
authors: SG
authors: Park
authors: Kwang-Hee
authors: KH
authors: Bae
authors: Sang Chul
authors: SC
authors: Lee
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology* / Q000201:enzymology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases; C505617:Dusp10 protein, mouse; D054637:Dual-Specificity Phosphatases; C093642:SB 203580
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