| First Author | Xu P | Year | 2015 |
| Journal | J Clin Invest | Volume | 125 |
| Issue | 7 | Pages | 2861-76 |
| PubMed ID | 26098212 | Mgi Jnum | J:224544 |
| Mgi Id | MGI:5688238 | Doi | 10.1172/JCI80941 |
| Citation | Xu P, et al. (2015) Estrogen receptor-alpha in medial amygdala neurons regulates body weight. J Clin Invest 125(7):2861-76 |
| abstractText | Estrogen receptor-alpha (ERalpha) activity in the brain prevents obesity in both males and females. However, the ERalpha-expressing neural populations that regulate body weight remain to be fully elucidated. Here we showed that single-minded-1 (SIM1) neurons in the medial amygdala (MeA) express abundant levels of ERalpha. Specific deletion of the gene encoding ERalpha (Esr1) from SIM1 neurons, which are mostly within the MeA, caused hypoactivity and obesity in both male and female mice fed with regular chow, increased susceptibility to diet-induced obesity (DIO) in males but not in females, and blunted the body weight-lowering effects of a glucagon-like peptide-1-estrogen (GLP-1-estrogen) conjugate. Furthermore, selective adeno-associated virus-mediated deletion of Esr1 in the MeA of adult male mice produced a rapid body weight gain that was associated with remarkable reductions in physical activity but did not alter food intake. Conversely, overexpression of ERalpha in the MeA markedly reduced the severity of DIO in male mice. Finally, an ERalpha agonist depolarized MeA SIM1 neurons and increased their firing rate, and designer receptors exclusively activated by designer drug-mediated (DREADD-mediated) activation of these neurons increased physical activity in mice. Collectively, our results support a model where ERalpha signals activate MeA neurons to stimulate physical activity, which in turn prevents body weight gain. |
