Dataset for: Oleoylethanolamide-induced anorexia in rats is associated with locomotor impairment

The endogenous peroxisome proliferator-activated receptor alpha (PPAR-α) agonist Oleoylethanolamide (OEA) inhibits eating in rodents, mainly by delaying the onset of meals. The underlying mechanisms of OEA-induced anorexia, however, remain unclear. Animals treated with high OEA doses were shown to display signs of discomfort and impaired locomotion. Therefore, we first examined whether the impaired locomotion may contribute to OEA’s anorectic effect. Second, it is controversial whether abdominal vagal afferents are necessary for OEA’s anorectic effect. Thus, we explored alternative peripheral neural pathways mediating IP OEA’s anorectic effect by performing a celiac-superior mesenteric ganglionectomy (CGX) or a subdiaphragmatic vagal deafferentation (SDA) alone or in combination. Exogenously administered OEA at a commonly used dose (10mg/kg BW, IP) concurrently reduced food intake and compromised locomotor activity. Attempts to dissociate both phenomena using the dopamine D2/D3 receptor agonist Quinpirole (1 mg/kg BW, SC) failed because Quinpirole antagonized both, OEA-induced locomotor impairment and delay in eating onset. CGX attenuated the prolongation of the latency to eat by IP OEA, but neither SDA nor CGX prevented IP OEA-induced locomotor impairment.
Our results indicate that IP OEA’s anorectic effect may be secondary to impaired locomotion rather than due to physiological satiety. They further confirm that vagal afferents do not mediate exogenous OEA’s anorectic effects, but suggest a role for spinal afferents in addition to an alternative, non-neuronal signaling route.

内源性过氧化物酶体增殖物激活受体α（peroxisome proliferator-activated receptor alpha, PPAR-α）激动剂油酰乙醇酰胺（Oleoylethanolamide, OEA）可在啮齿类动物中抑制摄食，其主要作用机制为延缓进餐起始时间。然而，OEA诱导厌食效应的潜在分子机制仍未明确。研究显示，给予高剂量OEA的动物会表现出不适症状及运动功能受损。为此，我们首先探究了运动功能受损是否参与OEA的厌食调控效应。其次，关于腹部迷走传入神经是否为OEA发挥厌食作用所必需这一问题尚存争议。因此，我们通过单独或联合实施腹腔-肠系膜上神经节切除术（celiac-superior mesenteric ganglionectomy, CGX）与膈下迷走神经传入切断术（subdiaphragmatic vagal deafferentation, SDA），探索介导腹腔注射（intraperitoneal, IP）OEA厌食效应的外周神经通路替代途径。以常用剂量（10mg/kg体重（body weight, BW），IP）外源性给予OEA，可同时降低摄食量并损害运动活性。使用多巴胺D2/D3受体激动剂喹吡罗（Quinpirole）（1mg/kg BW，皮下注射（subcutaneous, SC））试图分离这两种效应的尝试未获成功，因为喹吡罗可同时拮抗OEA诱导的运动功能受损与进餐起始延迟现象。CGX可缓解腹腔注射OEA所致的摄食潜伏期延长，但SDA与CGX均未能阻止OEA诱导的运动功能受损。
本研究结果表明，腹腔注射OEA的厌食效应可能继发于运动功能受损，而非生理性饱感介导。研究进一步证实，迷走传入神经并未参与外源性OEA的厌食调控，同时提示脊髓传入神经及非神经元信号通路可能在其中发挥替代作用。