GLP-1通過(guò)下丘腦回路增加小鼠和人類(lèi)的餐前飽腹感
2024.07.01近日，韓國(guó)國(guó)立首爾大學(xué)Hyung Jin Choi等研究人員合作發(fā)現(xiàn)，GLP-1通過(guò)下丘腦回路增加小鼠和人類(lèi)的餐前飽腹感。該項(xiàng)研究成果于2024年6月27日在線(xiàn)發(fā)表在《科學(xué)》雜志上。
研究人員給肥胖癥患者服用了GLP-1受體激動(dòng)劑（GLP-1RA）后，觀察到他們的餐前飽腹感增強(qiáng)了。對(duì)人類(lèi)和小鼠大腦樣本的分析結(jié)果表明，背內(nèi)側(cè)下丘腦（DMH）中的GLP-1R神經(jīng)元是編碼進(jìn)食前飽腹感的候選神經(jīng)元。對(duì)DMHGLP-1R神經(jīng)元進(jìn)行光遺傳操作可引起飽腹感。鈣成像顯示，這些神經(jīng)元積極參與了進(jìn)食前飽腹感的編碼。給予GLP-1RA會(huì)在進(jìn)食行為中選擇性地增加DMHGLP-1R神經(jīng)元的活性。
研究人員進(jìn)一步確定了DMHGLP-1R神經(jīng)元與弓狀NPY/AgRP神經(jīng)元（ARCNPY/AgRP）之間錯(cuò)綜復(fù)雜的相互作用，以調(diào)節(jié)食物攝入。這些研究結(jié)果揭示了GLP-1RA控制進(jìn)食前飽腹感的下丘腦機(jī)制，為肥胖和代謝性疾病提供了新的神經(jīng)靶點(diǎn)。
據(jù)介紹，GLP-1RA是有效的抗肥胖藥物。然而，GLP-1RA的確切中樞機(jī)制仍然難以捉摸。
附：英文原文
Title: GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans
Author: Kyu Sik Kim, Joon Seok Park, Eunsang Hwang, Min Jung Park, Hwa Yun Shin, Young Hee Lee, Kyung Min Kim, Laurent Gautron, Elizabeth Godschall, Bryan Portillo, Kyle Grose, Sang-Ho Jung, So Lin Baek, Young Hyun Yun, Doyeon Lee, Eunseong Kim, Jason Ajwani, Seong Ho Yoo, Ali D. Güler, Kevin W. Williams, Hyung Jin Choi
Issue&Volume: 2024-06-27
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 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 an intricate interplay between DMHGLP-1R neurons and arcuate NPY/AgRP neurons (ARCNPY/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.
DOI: adj2537
Source: https://www.science.org/doi/10.1126/science.adj2537
期刊信息
Science：《科學(xué)》，創(chuàng)刊于1880年。隸屬于美國(guó)科學(xué)促進(jìn)會(huì)，IF：63.714
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