ECE2015 Oral Communications Neuroendocrinology and pituitary-basic (5 abstracts)
Gonadotropin-inhibitory hormone signalling displays sexually dimorphic roles in the control of energy homeostasis: studies in the NPFF1 receptor null mouse
Silvia Leon 1, , Maria Jesus Vazquez 1, , Alexia Barroso 1, , David Garcia-Galiano 1 , Francisco Ruiz-Pino 1, , Maria Manfredi-Lozano 1, , Antonio Romero-Ruiz 1, , Miguel A Sanchez-Garrido 1, , Carlos Dieguez 3, , Ruben Nogueiras 3, , Juan Roa 1, , Leonor Pinilla 1, & Manuel Tena-Sempere 1,
1University of Cordoba, Cordoba, Spain; 2Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain; 3CIBERobn, Cordoba, Spain; 4University of Santiago de Compostela, Santiago de Compostela, Spain.
RF-amide-related peptide-3 (RFRP-3), the mammalian orthologue of the avian gonadotropin-inhibiting hormone (GnIH), has been proposed as major inhibitory signal for the reproductive axis, acting via the NPFF1 receptor (NPFF1R). In addition, RFRP-3 has been recently suggested to modulate feeding, with reported orexigenic actions; a function that might contribute to the integrative control of energy homeostasis and reproduction. However, characterisation of the metabolic effects of RFRP-3/GnIH signalling remains superficial and largely restricted to few pharmacological studies. As a means to address the putative physiological roles of GnIH/RFRP-3 signalling in the control of metabolic homeostasis, we report here the metabolic phenotyping of the first mouse line with constitutive inactivation of NPFF1R. Congenital elimination of NPFF1R did not alter adult body weight (BW) neither affected BW responses to high fat diet (HFD) in males. In contrast, NPFF1R null female mice tended to be slightly heavier and displayed exaggerated BW increases in response to obesogenic insults, such as HFD or ovariectomy. Conversely, NPFF1R KO males, but not females, fed on HFD showed perturbed glycaemic responses in glucose tolerance tests, even though basal glucose and insulin concentrations were not significantly different from WT levels. In addition, the patterns of food intake were affected in NPFF1R KOs of both sexes, with modest decreases in acute food intake and altered responses to leptin and ghrelin; feeding suppression following leptin administration was exaggerated in NPFF1R null mice, while the orexigenic responses to ghrelin were partially blunted in the absence of NPFF1R signalling. In sum, we provide herein the metabolic characterization of a mouse model of congenital elimination of the canonical receptor for GnIH/RFRP-3. While our data are compatible with a (modest) role of GnRH/RFRP-3 as orexigenic factor that mediates part of the effects of ghrelin on food intake, our study is the first to disclose the deleterious impact of the lack of NPFF1R signalling on BW and glucose homeostasis, which exaggerates the metabolic impact of concurrent obesogenic insults, such as HFD, in a sexually dimorphic manner.
Disclosure: This work was supported by grant BFU2011-025021 (Ministerio de Economía y Competitividad, Spain; co-funded with EU funds from FEDER Program) and Projects P08-CVI-03788 and P12-FQM-01943 (Junta de Andalucía, Spain).
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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