| First Author | Watanabe T | Year | 2015 |
| Journal | Biochem Biophys Res Commun | Volume | 468 |
| Issue | 1-2 | Pages | 196-201 |
| PubMed ID | 26523513 | Mgi Jnum | J:233200 |
| Mgi Id | MGI:5780943 | Doi | 10.1016/j.bbrc.2015.10.131 |
| Citation | Watanabe T, et al. (2015) Dehydroepiandrosterone-enhanced dual specificity protein phosphatase (DDSP) prevents diet-induced and genetic obesity. Biochem Biophys Res Commun 468(1-2):196-201 |
| abstractText | Dehydroepiandrosterone (DHEA) exerts a wide variety of therapeutic effects against medical disorders, such as diabetes and obesity. However, the molecular basis of DHEA action remains to be clarified. Previously, we reported that DHEA-enhanced dual specificity protein phosphatase, designated DDSP, is one of the target molecules of DHEA. To examine the role of DDSP in DHEA signaling, we generated mice that carry a DDSP transgene in which expression is driven by the CAG promoter (DDSP-Tg). DDSP-Tg mice weighed significantly less than wild-type (WT) control mice when a high fat diet was supplied (p < 0.01). No difference in food-intake or locomotor activity was found between DDSP-Tg and WT mice. Oxygen consumption of DDSP-Tg mice was higher than that of WT mice (p < 0.01), which suggested an increase in basal metabolism in DDSP-Tg mice. To further investigate the role of DDSP in genetic obese mice, DDSP-Tg mice with a db/db background were generated (DDSP-Tg db/db). We observed cancellation of obesity by the db/db mutation and development of a cachexic phenotype in DDSP-Tg db/db mice. In conclusion, our study shows that expression of DDSP leads to prevention of diet-induced and genetic (db/db) obesity. Anti-obese effects of DHEA might be mediated through DDSP, which might be a therapeutic target for intervention of obesity. |
