27-Hydroxycholesterol acts on estrogen receptor α expressed by POMC neurons in the arcuate nucleus to modulate feeding behavior-Reference-Cited by-同舟云学术

27-Hydroxycholesterol acts on estrogen receptor α expressed by POMC neurons in the arcuate nucleus to modulate feeding behavior

Published:2024-07-12 Issue:28 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Ye Hui¹²^ORCID,Yang Xiaohua²³,Feng Bing⁴^ORCID,Luo Pei²³^ORCID,Torres Irizarry Valeria C.²⁵^ORCID,Carrillo-Sáenz Leslie²⁵^ORCID,Yu Meng⁶^ORCID,Yang Yongjie⁶^ORCID,Eappen Benjamin P.⁶,Munoz Marcos David²^ORCID,Patel Nirali²^ORCID,Schaul Sarah²^ORCID,Ibrahimi Lucas²^ORCID,Lai Penghua²^ORCID,Qi Xinyue¹^ORCID,Zhou Yuliang¹^ORCID,Kota Maya²,Dixit Devin²^ORCID,Mun Madeline²,Liew Chong Wee²⁵^ORCID,Jiang Yuwei²⁵^ORCID,Wang Chunmei⁶^ORCID,He Yanlin⁴^ORCID,Xu Pingwen²⁵^ORCID

Affiliation:

1. School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 639798, Singapore.

2. Division of Endocrinology, Department of Medicine, The University of Illinois at Chicago, Chicago, IL 60612, USA.

3. Guangdong Laboratory of Lingnan Modern Agriculture and Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, 483 Wushan Road, Tianhe District, Guangzhou, Guangdong 510642, China.

4. Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.

5. Department of Physiology and Biophysics, The University of Illinois at Chicago, Chicago, IL 60612, USA.

6. Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Abstract

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 α (ERα) 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 ERα-dependent manner. In addition, we observed that inhibiting brain ERα, deleting ERα 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 ERα and modulation of the SK channel, inhibits food intake as a negative feedback mechanism against a surge in circulating cholesterol.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adi4746

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