Blais Anne, Drouin Gaëtan, Chaumontet Catherine, Voisin Thierry, Couvelard Anne, Even Patrick Christian, Couvineau Alain
UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, Paris, France.
INSERM U1149/ Inflammation Research Center (CRI), Paris-Diderot University, DHU UNITY, Faculté de Médecine Site Bichat, 16, rue H. Huchard, Paris, France.
PLoS One. 2017 Jan 13;12(1):e0169908. doi: 10.1371/journal.pone.0169908. eCollection 2017.
Orexin-A and -B are hypothalamic neuropeptides of 33 and 28-amino acids, which regulate many homeostatic systems including sleep/wakefulness states, energy balance, energy homeostasis, reward seeking and drug addiction. Orexin-A treatment was also shown to reduce tumor development in xenografted nude mice and is thus a potential treatment for carcinogenesis. The aim of this work was to explore in healthy mice the consequences on energy expenditure components of an orexin-A treatment at a dose previously shown to be efficient to reduce tumor development. Physiological approaches were used to evaluate the effect of orexin-A on food intake pattern, energy metabolism body weight and body adiposity. Modulation of the expression of brain neuropeptides and receptors including NPY, POMC, AgRP, cocaine- and amphetamine related transcript (CART), corticotropin-releasing hormone (CRH) and prepro-orexin (HCRT), and Y2 and Y5 neuropeptide Y, MC4 (melanocortin), OX1 and OX2 orexin receptors (Y2R, Y5R, MC4R, OX1R and OX2R, respectively) was also explored. Our results show that orexin-A treatment does not significantly affect the components of energy expenditure, and glucose metabolism but reduces intraperitoneal fat deposit, adiposity and the expression of several brain neuropeptide receptors suggesting that peripheral orexin-A was able to reach the central nervous system. These findings establish that orexin-A treatment which is known for its activity as an inducer of tumor cell death, do have minor parallel consequence on energy homeostasis control.
食欲素-A和食欲素-B是分别由33个和28个氨基酸组成的下丘脑神经肽，它们调节包括睡眠/觉醒状态、能量平衡、能量稳态、奖赏寻求和药物成瘾在内的多种稳态系统。食欲素-A治疗还被证明可减少异种移植裸鼠的肿瘤发生，因此是一种潜在的癌症治疗方法。这项工作的目的是在健康小鼠中探索以先前显示对减少肿瘤发生有效的剂量进行食欲素-A治疗对能量消耗组成部分的影响。采用生理学方法评估食欲素-A对食物摄入模式、能量代谢、体重和身体肥胖的影响。还探讨了包括神经肽Y（NPY）、阿黑皮素原（POMC）、刺鼠肽蛋白（AgRP）、可卡因和苯丙胺调节转录肽（CART）、促肾上腺皮质激素释放激素（CRH）和前食欲素原（HCRT）以及神经肽Y的Y2和Y5受体、黑皮质素4（MC4）、食欲素OX1和OX2受体（分别为Y2R、Y5R、MC4R、OX1R和OX2R）表达的调节作用。我们的结果表明，食欲素-A治疗对能量消耗和葡萄糖代谢的组成部分没有显著影响，但可减少腹膜内脂肪沉积、肥胖以及几种脑内神经肽受体的表达，这表明外周食欲素-A能够到达中枢神经系统。这些发现表明，以作为肿瘤细胞死亡诱导剂的活性而闻名的食欲素-A治疗，在能量稳态控制方面确实有轻微的并行影响。
