ECE2018 Guided Posters Neuroendocrinology (11 abstracts)
Reproductive and metabolic consequences of AMP-Activated Protein Kinase (AMPK) ablation in GnRH neurons
Alexia Barroso 1, , Delphine Franssen 1, , Francisco Ruiz-Pino 1, , Maria Jesus Vázquez 1, , David García-Galiano 1, , Juan Manuel Castellano 1, , Rocío Onieva 1, , Ana Belén Rodríguez 1, , Francisco Gaytán 1, , Carlos Diéguez 5, , Leonor Pinilla 1, , Miguel López 5, , Juan Roa 1, & Manuel Tena-Sempere 1,
1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Cordoba, Spain; 2Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Hospital Universitario Reina Sofía, Cordoba, Spain; 3CIBER Fisiopatología de la Obesidad y Nutrición, Cordoba, Spain; 4Univeristy of Liège, Liège, Belgium; 5CIBER Fisiopatología de la Obesidad y Nutrición, Galicia, Spain; 6Department of Physiology, University of Santiago de Compostela, Galicia, Spain.
GnRH neurons are the final output of the brain controlling reproduction. These neurons receive information from multiple central and peripheral signals, ranging from gonadal steroids to metabolic cues and brain neuropeptides, to regulate their activity. AMP-activated protein kinase (AMPK) is an intracellular sensor, activated by energy deficiency, involved in the regulation of the cellular and whole-body energy homeostasis. Previous in vitro studies suggested the participation of AMPK in the negative regulation of GnRH neuronal excitability in response to glucose deprivation. Nonetheless, the physiological relevance of AMPK signaling in GnRH neurons for the metabolic control of the reproductive function remains unknown. In this work, we aimed to explore the roles of AMPK signaling in GnRH neurons by generating a transgenic mouse, named GAMKO, with congenital elimination of the catalytic AMPK alpha-1 subunit specifically in this neuronal population. Ablation of AMPK in GnRH neurons resulted in advanced puberty onset in female, but not male mice. Moreover, acyclic GAMKO females, due to chronic caloric restriction, had a faster recovery of the estrous cyclicity after re-feeding, compared to control mice. Both features are compatible with unrestrained GnRH secretion in the absence of AMPK, which would drive a negative valence when become active (e.g., in conditions of negative energy balance). In addition, GAMKO females showed enhanced responsiveness to GnRH administration, in terms of LH secretion. On the other hand, adult GAMKO mice had increased fat mass and body weight, being already evident in males at the time of puberty. All in all, our data are the first in describing the potential role of AMPK in GnRH neurons for the regulation of reproduction and metabolism. Further characterization of the reproductive (LH pulsatility, ovarian histology) and metabolic (insulin resistance, energy consumption) phenotype of GAMKO mice is currently ongoing in order to fully disclose the physiological function of this key energy sensor in the dynamic regulation of GnRH neurons and the bodily functions controlled thereby.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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