A1 Refereed original research article in a scientific journal
Central Ceramide Signaling Mediates Obesity-Induced Precocious Puberty
Authors: Heras Violeta, Castellano Juan Manuel, Fernandois Daniela, Velasco Inmaculada, Rodriguez-Vazquez Elvira, Roa Juan, Vazquez Maria Jesus, Ruiz-Pino Francisco, Rubio Matias, Pineda Rafael, Torres Encarnacion, Avendano Maria Soledad, Paredes Alfonso, Pinilla Leonor, Belsham Denise, Dieguez Carlos, Gaytan Francisco, Casals Nuria, Lopez Miguel, Tena-Sempere Manuel
Publisher: CELL PRESS
Publication year: 2020
Journal: Cell Metabolism
Journal name in source: CELL METABOLISM
Journal acronym: CELL METAB
Volume: 32
Issue: 6
First page : 951
Last page: 966
Number of pages: 25
ISSN: 1550-4131
eISSN: 1932-7420
DOI: https://doi.org/10.1016/j.cmet.2020.10.001
Web address : https://www.sciencedirect.com/science/article/pii/S1550413120305349?via%3Dihub
Childhood obesity, especially in girls, is frequently bound to earlier puberty, which is linked to higher disease burden later in life. The mechanisms underlying this association remain elusive. Here we show that brain ceramides participate in the control of female puberty and contribute to its alteration in early-onset obesity in rats. Postnatal overweight caused earlier puberty and increased hypothalamic ceramide content, while pharmacological activation of ceramide synthesis mimicked the pubertal advancement caused by obesity, specifically in females. Conversely, central blockade of de novo ceramide synthesis delayed puberty and prevented the effects of the puberty-activating signal, kisspeptin. This phenomenon seemingly involves a circuit encompassing the paraventricular nucleus (PVN) and ovarian sympathetic innervation. Early-onset obesity enhanced PVN expression of SPTLC1, a key enzyme for ceramide synthesis, and advanced the maturation of the ovarian noradrenergic system. In turn, obesity-induced pubertal precocity was reversed by virogenetic suppression of SPTLC1 in the PVN. Our data unveil a pathway, linking kisspeptin, PVN ceramides, and sympathetic ovarian innervation, as key for obesity-induced pubertal precocity.
