Metabolic regulation of female puberty via hypothalamic AMPK–kisspeptin signaling

• DOI: 10.1073/pnas.1802053115
• Publication Date: 2018-10-22T19:20:18Z
• Authors: Juan Roa; Alexia Barroso; Francisco Ruiz-Pino; Maria Jesus Vázquez; Patricia Seoane-C...; Noelia Martínez-S...; David García-Galiano; Tuncay Ilhan; Rafael Pineda; Silvia León; Maria Manfredi-Lo...; Violeta Heras; Matti Poutanen; Juan M. Castellano; Francisco Gaytan; Carlos Diéguez; Leonor Pinilla; Miguel López; Manuel Tena-Sempere
• Keywords: Kisspeptin; Delayed puberty

Significance The age of puberty in humans is changing via unknown mechanisms, although metabolic alterations childhood are blamed as a major contributing factor. Perturbations pubertal timing posed with increased risk later cardiometabolic diseases and reduced life expectancy, urging better understanding the molecular basis for these phenomena. We describe mechanism whereby main cellular energy sensor, AMPK, operates population hypothalamic neurons, named Kiss1, which produce puberty-activating signal, kisspeptin, to metabolically control onset. This neuroendocrine circuit provides link between conditions negative balance delayed timing, repressive AMPK–Kiss1 pathway, may become druggable target disordered puberty, especially origin.