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Nitric Oxide Acts in the Rat Dorsomedial Hypothalamus to Increase High Fat Food Intake and Glutamate Transmission.
Neuroscience ( IF 2.9 ) Pub Date : 2020-06-05 , DOI: 10.1016/j.neuroscience.2020.05.039
Emily I Poole 1 , Victoria A Rust 1 , Karen M Crosby 1
Affiliation  

The dorsomedial nucleus of the hypothalamus (DMH) plays an important role in the regulation of energy intake and expenditure. Numerous appetite-regulatory signals present in the DMH, including nitric oxide (NO) and endogenous cannabinoids (eCBs), act to regulate food intake, but whether these signals are involved in regulating high fat food intake remains unknown. We therefore asked whether NO and eCBs, administered alone or in combination, would influence the consumption of high fat food in rats. We implanted bilateral guide cannulas in the DMH of young, male Sprague-Dawley rats for microinjection of vehicle, NO (via the precursor l-arginine), the eCB 2-arachidonylglycerol (2-AG), or a combination of the two signals. Following the intrahypothalamic injections, both high fat food intake and body weight were measured for two hours at which point brains were removed and sectioned to confirm cannula placement in the DMH. Here we show that l-arginine significantly increases high fat food intake when administered into the DMH. This effect is abolished in the presence of 2-AG, which alone has no effect on high fat food intake or body weight. The l-arginine-induced increase in high fat food intake is dependent on NO synthesis, as it is prevented with the NO synthase inhibitor, l-NAME. We also demonstrate that l-arginine increases glutamate transmission onto DMH neurons, an effect that also requires NO synthesis and is abolished with 2-AG. Together, these data indicate that NO acts in the DMH to regulate the consumption of high fat food, possibly by enhancing glutamate signaling at DMH synapses.



中文翻译:

一氧化氮在大鼠下丘脑下丘脑中起作用,以增加高脂肪食物的摄取和谷氨酸的传递。

下丘脑(DMH)的背核在能量摄入和消耗的调节中起重要作用。DMH中存在大量的食欲调节信号,包括一氧化氮(NO)和内源性大麻素(eCBs)起到调节食物摄入的作用,但是这些信号是否参与调节高脂肪食物的摄入尚不清楚。因此,我们询问单独或联合施用NO和eCB是否会影响大鼠高脂食物的摄入。我们将双侧引导插管植入年轻的雄性Sprague-Dawley大鼠的DMH中,以进行微注射媒介物NO(通过前体l-精氨酸),eCB 2-花生四烯酸甘油酯(2-AG)或两个信号的组合。下丘脑内注射后,测量两个小时的高脂肪食物摄入量和体重,然后取出大脑并切成薄片以确认套管在DMH中的位置。在这里,我们表明,时给药到DMH精氨酸显著增加高脂肪食物的摄入。在存在2-AG的情况下,该作用消失了,2-AG仅对高脂肪食物的摄入量或体重没有影响。在高脂肪食物的摄取精氨酸引起的增加是依赖于NO的合成,因为它防止与NO合酶抑制剂,-NAME。我们还表明,-精氨酸增加了谷氨酸向DMH神经元的传递,这种作用也不需要合成,并且被2-AG废除了。这些数据加在一起表明NO可能通过增强DMH突触处的谷氨酸信号传导而在DMH中调节高脂食物的消耗。

更新日期:2020-06-25
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