Abstract
Previous reports have suggested that hypothalamic urocortin 1 (Ucn1) exerts inhibitory control on energy metabolism as direct paraventricular nucleus injections dose-dependently decrease the respiratory energy exchange ratio (RER). Other evidence indicates that Ucn1 injections into the lateral septum may alter metabolic function. Consequently, the present study was designed to further characterize the effects of lateral septal Ucn1 signaling on eating and energy metabolism of adult Sprague-Dawley rats. Ucn1 was infused at the onset of the nocturnal cycle at doses of 10 - 100 pmol. In both females and males the peptide elicited a reliable suppression of food intake and significantly lowered RER over a 4 h postinjection period. The decrease in RER is consistent with enhanced lipid oxidation. Overall these findings suggest that, similar to the paraventricular nucleus, the lateral septum is a critical site of action in mediating the effects of Ucn1 on food intake and energy substrate utilization.
Highlights
The mammalian peptide urocortin 1 (Ucn1) shares a 45% sequence identity with corticotropin-releasing hormone (CRH) and binds with high affinity to CRH1 and CRH2 receptor subtypes [1,2,3,4,5]
Along with urocortin 2 (Ucn2) and urocortin 3 (Ucn3), Ucn1 has been implicated in the control of stress and anxiety, when injected into the basolateral amygdala and associated limbic structures [6,7,8,9,10,11,12]
With respect to food intake, the anorexigenic effects of Ucn1 have been observed after injection into the supraoptic nucleus and the paraventricular nucleus (PVN) of the hypothalamus [16,17,19]
Summary
The mammalian peptide urocortin 1 (Ucn1) shares a 45% sequence identity with corticotropin-releasing hormone (CRH) and binds with high affinity to CRH1 and CRH2 receptor subtypes [1,2,3,4,5]. With respect to food intake, the anorexigenic effects of Ucn have been observed after injection into the supraoptic nucleus and the paraventricular nucleus (PVN) of the hypothalamus [16,17,19] The latter region is extensively implicated in homeostatic function [20,21,22]. The dorsal raphe nucleus appears to be responsive to urocortin as microinjection of Ucn into this brain region elicits significant reductions in the amount of food consumed and in body weight gain [23] These findings are in agreement with other work showing that ventricular administration of Ucn induces alterations in metabolic control, and in particular, via thermoregulatory mechanisms [24].
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