Science (New York, N.Y.) · 2024
GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Kim Kyu Sik, Park Joon Seok, Hwang Eunsang, Park Min Jung, Shin Hwa Yun, Lee Young Hee, Kim Kyung Min, Gautron Laurent, Godschall Elizabeth, Portillo Bryan, Grose Kyle, Jung Sang-Ho, Baek So Lin, Yun Young Hyun, Lee Doyeon, Kim Eunseong, Ajwani Jason, Yoo Seong Ho, Güler Ali D, Williams Kevin W, Choi Hyung Jin
Аннотация
Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are effective antiobesity drugs. However, the precise central mechanisms of GLP-1RAs remain elusive. We administered GLP-1RAs to patients with obesity and observed a heightened sense of preingestive satiation. Analysis of human and mouse brain samples pinpointed GLP-1 receptor (GLP-1R) neurons in the dorsomedial hypothalamus (DMH) as candidates for encoding preingestive satiation. Optogenetic manipulation of DMHGLP-1R neurons caused satiation. Calcium imaging demonstrated that these neurons are actively involved in encoding preingestive satiation. GLP-1RA administration increased the activity of DMHGLP-1R neurons selectively during eating behavior. We further identified that an intricate interplay between DMHGLP-1R neurons and neuropeptide Y/agouti-related peptide neurons of the arcuate nucleus (ARCNPY/AgRP neurons) occurs to regulate food intake. Our findings reveal a hypothalamic mechanism through which GLP-1RAs control preingestive satiation, offering previously unexplored neural targets for obesity and metabolic diseases.