Metabolic regulation of female puberty via hypothalamic AMPK-kisspeptin signaling
| Autor: | Rafael Pineda, David Garcia-Galiano, María Jesús Vázquez, Patricia Seoane-Collazo, Heras, Noelia Martínez-Sánchez, Alexia Barroso, Francisco Ruiz-Pino, Juan M. Castellano, Manuel Tena-Sempere, T. Ilhan, C. Dieguez, Matti Poutanen, Leonor Pinilla, F Gaytan, Juan Carlos Roa, Miguel López, S. Leon, anfredi-Lozano M |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
AMPK
0301 basic medicine Delayed puberty puberty medicine.medical_specialty Time Factors Population AMP-Activated Protein Kinases Biology ta3111 Energy homeostasis Animals Genetically Modified Mice 03 medical and health sciences Kisspeptin Internal medicine medicine Animals Sexual Maturation Rats Wistar education Protein kinase A Caloric Restriction Neurons Kisspeptins education.field_of_study Multidisciplinary Arc (protein) Estradiol Malnutrition Arcuate Nucleus of Hypothalamus Gene Expression Regulation Developmental Kiss1 Luteinizing Hormone Ribonucleotides Aminoimidazole Carboxamide energy balance Rats undernutrition Mice Inbred C57BL 030104 developmental biology Endocrinology Metabolic regulation PNAS Plus Female medicine.symptom Luteinizing hormone Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 115(45):E10758-E10767 |
| ISSN: | 0027-8424 |
| Popis: | Conditions of metabolic distress, from malnutrition to obesity, impact, via as yet ill-defined mechanisms, the timing of puberty, whose alterations can hamper later cardiometabolic health and even life expectancy. AMP-activated protein kinase (AMPK), the master cellular energy sensor activated in conditions of energy insufficiency, has a major central role in whole-body energy homeostasis. However, whether brain AMPK metabolically modulates puberty onset remains unknown. We report here that central AMPK interplays with the puberty-activating gene, Kiss1, to control puberty onset. Pubertal subnutrition, which delayed puberty, enhanced hypothalamic pAMPK levels, while activation of brain AMPK in immature female rats substantially deferred puberty. Virogenetic overexpression of a constitutively active form of AMPK, selectively in the hypothalamic arcuate nucleus (ARC), which holds a key population of Kiss1 neurons, partially delayed puberty onset and reduced luteinizing hormone levels. ARC Kiss1 neurons were found to express pAMPK, and activation of AMPK reduced ARC Kiss1 expression. The physiological relevance of this pathway was attested by conditional ablation of the AMPK alpha 1 subunit in Kiss1 cells, which largely prevented the delay in puberty onset caused by chronic subnutrition. Our data demonstrate that hypothalamic AMPK signaling plays a key role in the metabolic control of puberty, acting via a repressive modulation of ARC Kiss1 neurons in conditions of negative energy balance. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|