최형진 (서울대학교 자연과학대학 뇌인지과학과, 의과대학 의과학과/해부학교실) | 한빛사논문 > 한빛사

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서울대학교 자연과학대학 뇌인지과학과, 의과대학 의과학과/해부학교실

Science, Jun 27 2024, | https://doi.org/10.1126/science.adj2537 GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans

Kyu Sik Kim ^{1 †}, Joon Seok Park ^{1 †}, Eunsang Hwang ^{2 †}, Min Jung Park ^{1 3}, Hwa Yun Shin ¹, Young Hee Lee ¹, Kyung Min Kim ¹, Laurent Gautron ², Elizabeth Godschall ⁴, Bryan Portillo ², Kyle Grose ², Sang-Ho Jung ¹, So Lin Baek ¹, Young Hyun Yun ⁵, Doyeon Lee ^{1 6}, Eunseong Kim ¹, Jason Ajwani ², Seong Ho Yoo ⁷, Ali D Güler ⁴, Kevin W Williams ^{2 *}, Hyung Jin Choi ^{1 5 8 9 10 *}

¹Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.

²Center for Hypothalamic Research, Department of Internal Medicine, Peter O'Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX, USA.

³Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Republic of Korea.

⁴Department of Biology, University of Virginia, Charlottesville, VA, USA.

⁵Department of Anatomy and Cell Biology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.

⁶Queen Square Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.

⁷Department of Forensic Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Seoul, Republic of Korea.

⁸Neuroscience Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.

⁹Wide River Institute of Immunology, Seoul National University, 101 Dabyeonbat-gil, Hwachon-myeon, Gangwon-do 25159, Republic of Korea.

¹⁰Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Republic of Korea.

^†These authors contributed equally
^*Corresponding authors: correspondence to Kevin W Williams or Hyung Jin Choi

Abstract

GLP-1 receptor agonists (GLP-1RAs) are effective anti-obesity drugs. However, the precise central mechanisms of GLP-1RAs remain elusive. We administered GLP-1RAs to obese patients and observed heightened sense of preingestive satiation. Analysis of human and mouse brain samples pinpointed GLP-1R neurons in the dorsomedial hypothalamus (DMH) as candidates for encoding preingestive satiation. Optogenetic manipulation of DMH^GLP-1R neurons caused satiation. Calcium imaging demonstrated that these neurons are actively involved in encoding preingestive satiation. GLP-1RA administration increased the activity of DMH^GLP-1R neurons selectively during eating behavior. We further identified an intricate interplay between DMH^GLP-1R neurons and arcuate NPY/AgRP neurons (ARC^NPY/AgRP), to regulate food intake. Our findings reveal a hypothalamic mechanism through which GLP-1RAs control preingestive satiation, offering novel neural targets for obesity and metabolic diseases.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-28)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 뇌인지과학

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