Oleoylethanolamide-induced anorexia in rats is associated with locomotor impairment

Abstract

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 (10 mg/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, nonneuronal signaling route.

A systematic review of the effects of oleoylethanolamide, a high‐affinity endogenous ligand of PPAR‐α, on the management and prevention of obesity

“…The biochemical structure of OEA is presented in Figure . OEA is derived from oleic acid (OA), a monounsaturated fatty acid, which has beneficial effects on body composition and regional fat distribution . The role of OEA in the modulation of food intake and weight management makes it an attractive molecule requiring further exploration in obesogenic environments.…”

“…OEA is derived from oleic acid (OA), a monounsaturated fatty acid, which has beneficial effects on body composition and regional fat distribution. [9][10][11][12][13][14] The role of OEA in the modulation of food intake and weight management makes it an attractive molecule requiring further exploration in obesogenic environments. Accordingly, this systematic review aimed to investigate the effects of OEA, as a high-affinity endogenous ligand of peroxisome proliferator-activated receptor alpha (PPAR-α), on the obesity management, with emphasis on its physiological roles and possible mechanisms of action in energy homeostasis.…”

Specific shifts in the endocannabinoid system in hibernating brown bears

“…Consequences of high levels of circulating OEA have been studied in non-hibernating rodents. Intraperitoneal OEA administration in rats notably impairs locomotor activity, which is supported by a decrease in ambulation, an increase of the time spent in inactivity, and the presence of signs of catalepsy [68,72]. We thus can hypothesize that a higher amount of plasma OEA during bear hibernation can participate in the maintenance of prolonged physical inactivity.…”

Specific shifts in the endocannabinoid system in hibernating brown bears

“…Consequences of high levels of circulating OAE have been studied in nonhibernating rodents. Intraperitoneal OEA administration in rats notably impairs locomotor activity, which is supported by a decrease in ambulation, an increase of the time spent in inactivity, and the presence of signs of catalepsy [52,54]. We thus can hypothesize that a higher amount of plasma OEA during bear hibernation can participate in the maintenance of prolonged physical inactivity.…”