Ghrelin-responsive mediobasal hypothalamic neurons mediate exercise-associated food intake and exercise endurance.
Ghrelin-responsive mediobasal hypothalamic neurons mediate exercise-associated food intake and exercise endurance.
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DOI：
10.1172/jci.insight.172549
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发表时间：
2023-12-22
期刊：
影响因子：
8
通讯作者：
Zigman, Jeffrey M.
中科院分区：
文献类型：
--
作者：
Singh, Omprakash;Ogden, Sean B.;Varshney, Salil;Shankar, Kripa;Gupta, Deepali;Paul, Subhojit;Osborne-Lawrence, Sherri;Richard, Corine P.;Metzger, Nathan P.;Lawrence, Connor;Mercado, Luis Leon;Zigman, Jeffrey M.
以前的研究表明，促食欲素Ghrelin是运动耐力和运动后摄食反应的中介。具体地说，当小鼠在跑步机上进行长达一小时的高强度间歇运动(HIIE)时，它们的血浆Ghrelin水平几乎翻了一番。此外，生长激素促分泌素受体缺失(GHSR-Null)小鼠在HIIE后食物摄入量减少，在更长的分步运动耐力方案中跑步距离(直到筋疲力尽的时间)缩短。为了研究Ghrelin反应的下丘脑内侧基底核(MBH)神经元是否介导了这些效应，我们通过立体定向将设计药物病毒AAV2-hSyn-DIO-HM4(Gi)-mCherry特异性激活的抑制设计受体转移到表达由GHSR启动子指导的Cre重组酶的GHSR-IRES-CRE小鼠的MBH中。我们发现，对表达GHSR的MBH神经元的化学发生抑制(在传递氯氮平-N-氧化物时)1)抑制HIIE后的食物摄入量，2)减少最大跑步距离，并在运动耐力方案中提高血糖和血乳酸水平，3)减少服用Ghrelin后的食物摄入量，4)不影响糖耐量。此外，HIIE还增加了MBH GHSR的表达。这些结果表明，Ghrelin反应的MBH神经元的激活是对HIIE的正常摄食反应和在运动耐力方案中表现出的正常运动量所必需的。
Previous studies have implicated the orexigenic hormone ghrelin as a mediator of exercise endurance and the feeding response postexercise. Specifically, plasma ghrelin levels nearly double in mice when they are subjected to an hour-long bout of high-intensity interval exercise (HIIE) using treadmills. Also, growth hormone secretagogue receptor–null (GHSR-null) mice exhibit decreased food intake following HIIE and diminished running distance (time until exhaustion) during a longer, stepwise exercise endurance protocol. To investigate whether ghrelin-responsive mediobasal hypothalamus (MBH) neurons mediate these effects, we stereotaxically delivered the inhibitory designer receptor exclusively activated by designer drugs virus AAV2-hSyn-DIO-hM4(Gi)-mCherry to the MBH of Ghsr-IRES-Cre mice, which express Cre recombinase directed by the Ghsr promoter. We found that chemogenetic inhibition of GHSR-expressing MBH neurons (upon delivery of clozapine-N-oxide) 1) suppressed food intake following HIIE, 2) reduced maximum running distance and raised blood glucose and blood lactate levels during an exercise endurance protocol, 3) reduced food intake following ghrelin administration, and 4) did not affect glucose tolerance. Further, HIIE increased MBH Ghsr expression. These results indicate that activation of ghrelin-responsive MBH neurons is required for the normal feeding response to HIIE and the usual amount of running exhibited during an exercise endurance protocol.
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