| First Author | Ye H | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 28 | Pages | eadi4746 |
| PubMed ID | 38996023 | Mgi Jnum | J:352295 |
| Mgi Id | MGI:7665634 | Doi | 10.1126/sciadv.adi4746 |
| Citation | Ye H, et al. (2024) 27-Hydroxycholesterol acts on estrogen receptor alpha expressed by POMC neurons in the arcuate nucleus to modulate feeding behavior. Sci Adv 10(28):eadi4746 |
| abstractText | Oxysterols are metabolites of cholesterol that regulate cholesterol homeostasis. Among these, the most abundant oxysterol is 27-hydroxycholesterol (27HC), which can cross the blood-brain barrier. Because 27HC functions as an endogenous selective estrogen receptor modulator, we hypothesize that 27HC binds to the estrogen receptor alpha (ERalpha) in the brain to regulate energy balance. Supporting this view, we found that delivering 27HC to the brain reduced food intake and activated proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (POMC(ARH)) in an ERalpha-dependent manner. In addition, we observed that inhibiting brain ERalpha, deleting ERalpha in POMC neurons, or chemogenetic inhibition of POMC(ARH) neurons blocked the anorexigenic effects of 27HC. Mechanistically, we further revealed that 27HC stimulates POMC(ARH) neurons by inhibiting the small conductance of the calcium-activated potassium (SK) channel. Together, our findings suggest that 27HC, through its interaction with ERalpha and modulation of the SK channel, inhibits food intake as a negative feedback mechanism against a surge in circulating cholesterol. |
