| First Author | Zhu L | Year | 2015 |
| Journal | Endocrinology | Volume | 156 |
| Issue | 12 | Pages | 4474-91 |
| PubMed ID | 26375425 | Mgi Jnum | J:232752 |
| Mgi Id | MGI:5780024 | Doi | 10.1210/en.2015-1660 |
| Citation | Zhu L, et al. (2015) The ERalpha-PI3K Cascade in Proopiomelanocortin Progenitor Neurons Regulates Feeding and Glucose Balance in Female Mice. Endocrinology 156(12):4474-91 |
| abstractText | Estrogens act upon estrogen receptor (ER)alpha to inhibit feeding and improve glucose homeostasis in female animals. However, the intracellular signals that mediate these estrogenic actions remain unknown. Here, we report that anorexigenic effects of estrogens are blunted in female mice that lack ERalpha specifically in proopiomelanocortin (POMC) progenitor neurons. These mutant mice also develop insulin resistance and are insensitive to the glucose-regulatory effects of estrogens. Moreover, we showed that propyl pyrazole triol (an ERalpha agonist) stimulates the phosphatidyl inositol 3-kinase (PI3K) pathway specifically in POMC progenitor neurons, and that blockade of PI3K attenuates propyl pyrazole triol-induced activation of POMC neurons. Finally, we show that effects of estrogens to inhibit food intake and to improve insulin sensitivity are significantly attenuated in female mice with PI3K genetically inhibited in POMC progenitor neurons. Together, our results indicate that an ERalpha-PI3K cascade in POMC progenitor neurons mediates estrogenic actions to suppress food intake and improve insulin sensitivity. |
