Role of orexin-A in the ventrolateral preoptic area on components of total energy expenditure.
Role of orexin-A in the ventrolateral preoptic area on components of total energy expenditure.
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DOI：
10.1038/ijo.2017.92
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Teske JA
中科院分区：
文献类型：
--
作者：
Coborn JE;DePorter DP;Mavanji V;Sinton CM;Kotz CM;Billington CJ;Teske JA
确定总能量消耗（EE）的组分是否受到食欲素受体（OXR 1和OXR 2）刺激或双重食欲素受体拮抗剂（DORA）的拮抗作用的影响与肥胖治疗相关。食欲素受体刺激通过增加总EE和自发体力活动（SPA）期间的EE来减少体重增加。本研究的目的是确定腹外侧视前区（VLPO）中的DORA（TCS-1102）是否减少食欲素-A诱导的觉醒、SPA、总EE和睡眠、休息、清醒和SPA期间的EE，以及单独的DORA是否减少总EE及其组分。我们假设：（1）DORA将减少食欲素-A诱导的觉醒、SPA、总EE组分的增加、睡眠减少和睡眠期间的EE，和（2）单独的DORA将减少基线水平的增加。（非刺激）SPA和总EE。睡眠，觉醒，微量注射DORA后测定SPA和EE图1显示了在具有靶向VLPO的单侧插管的雄性Sprague-Dawley大鼠的VLPO中TCS-1102和食欲素-A的表达。根据时间戳数据确定总EE的单个组分。DORA可降低orexin-A引起的觉醒、SPA、总EE和SPA、清醒、休息和睡眠期间EE的增加（P < 0.05）。Orexin-A在注射后1h显著减少睡眠并显著增加睡眠期间的EE（P < 0.05）。此外，DORA单独使用可显著降低总EE、睡眠期间（NREM和REM）的EE以及注射后2 h的静息EE（P < 0.05）。这些数据表明，食欲素-A通过在SPA、休息和睡眠期间增加EE来刺激总EE，从而减少体重增加。单独使用DORA的剩余效应包括总EE和睡眠和休息期间EE的减少，这可能会促进体重增加。
Identifying whether components of total energy expenditure (EE) are affected by orexin receptor (OXR1 and OXR2) stimulation or antagonism with dual orexin receptor antagonists (DORAs) has relevance for obesity treatment. Orexin receptor stimulation reduces weight gain by increasing total EE and EE during spontaneous physical activity (SPA). The purpose of this study was to determine if a DORA (TCS-1102) in the ventrolateral preoptic area (VLPO) reduced orexin-A-induced arousal, SPA, total EE and EE during sleep, rest, wake and SPA and whether the DORA alone reduced total EE and its components. We hypothesized that: (1) a DORA would reduce orexin-A induced increases in arousal, SPA, components of total EE, reductions in sleep and the EE during sleep and (2) the DORA alone would reduce baseline (non-stimulated) SPA and total EE. Sleep, wakefulness, SPA and EE were determined after microinjection of the DORA (TCS-1102) and orexin-A in the VLPO of male Sprague–Dawley rats with a unilateral cannula targeted towards the VLPO. Individual components of total EE were determined based on time-stamped data. The DORA reduced orexin-A-induced increases in arousal, SPA, total EE and EE during SPA, wake, rest and sleep 1 h post injection (P < 0.05). Orexin-A significantly reduced sleep and significantly increased EE during sleep 1 h post injection (P < 0.05). Furthermore, the DORA alone significantly reduced total EE, EE during sleep (NREM and REM) and resting EE 2 h post injection (P < 0.05). These data suggest that orexin-A reduces weight gain by stimulating total EE through increases in EE during SPA, rest and sleep. Residual effects of the DORA alone include decreases in total EE and EE during sleep and rest, which may promote weight gain.
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