-transparent.png){kind=logo}
Central Ceramide Signaling Mediates Obesity-Induced Precocious Puberty. 2020
Violeta Heras, and
Juan Manuel Castellano, and
Daniela Fernandois, and
Inmaculada Velasco, and
Elvira Rodríguez-Vazquez, and
Juan Roa, and
Maria Jesus Vazquez, and
Francisco Ruiz-Pino, and
Matias Rubio, and
Rafael Pineda, and
Encarnacion Torres, and
Maria Soledad Avendaño, and
Alfonso Paredes, and
Leonor Pinilla, and
Denise Belsham, and
Carlos Diéguez, and
Francisco Gaytán, and
Nuria Casals, and
Miguel López, and
Manuel Tena-Sempere
Instituto Maimónides de Investigation Biomédica de Córdoba (IMIBIC), Department of Cell Biology, Physiology and Immunology, University of Córdoba and Hospital Universitario Reina Sofia, 14004 Córdoba, Spain.
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.
Related Publications
Violeta Heras, and
Juan Manuel Castellano, and
Daniela Fernandois, and
Inmaculada Velasco, and
Elvira Rodríguez-Vazquez, and
Juan Roa, and
Maria Jesus Vazquez, and
Francisco Ruiz-Pino, and
Matias Rubio, and
Rafael Pineda, and
Encarnacion Torres, and
Maria Soledad Avendaño, and
Alfonso Paredes, and
Leonor Pinilla, and
Denise Belsham, and
Carlos Diéguez, and
Francisco Gaytán, and
Nuria Casals, and
Miguel López, and
Manuel Tena-Sempere
January 2022,
Frontiers in endocrinology,
Violeta Heras, and
Juan Manuel Castellano, and
Daniela Fernandois, and
Inmaculada Velasco, and
Elvira Rodríguez-Vazquez, and
Juan Roa, and
Maria Jesus Vazquez, and
Francisco Ruiz-Pino, and
Matias Rubio, and
Rafael Pineda, and
Encarnacion Torres, and
Maria Soledad Avendaño, and
Alfonso Paredes, and
Leonor Pinilla, and
Denise Belsham, and
Carlos Diéguez, and
Francisco Gaytán, and
Nuria Casals, and
Miguel López, and
Manuel Tena-Sempere
December 1986,
Tijdschrift voor kindergeneeskunde,
Violeta Heras, and
Juan Manuel Castellano, and
Daniela Fernandois, and
Inmaculada Velasco, and
Elvira Rodríguez-Vazquez, and
Juan Roa, and
Maria Jesus Vazquez, and
Francisco Ruiz-Pino, and
Matias Rubio, and
Rafael Pineda, and
Encarnacion Torres, and
Maria Soledad Avendaño, and
Alfonso Paredes, and
Leonor Pinilla, and
Denise Belsham, and
Carlos Diéguez, and
Francisco Gaytán, and
Nuria Casals, and
Miguel López, and
Manuel Tena-Sempere
January 2008,
Endokrynologia Polska,
Violeta Heras, and
Juan Manuel Castellano, and
Daniela Fernandois, and
Inmaculada Velasco, and
Elvira Rodríguez-Vazquez, and
Juan Roa, and
Maria Jesus Vazquez, and
Francisco Ruiz-Pino, and
Matias Rubio, and
Rafael Pineda, and
Encarnacion Torres, and
Maria Soledad Avendaño, and
Alfonso Paredes, and
Leonor Pinilla, and
Denise Belsham, and
Carlos Diéguez, and
Francisco Gaytán, and
Nuria Casals, and
Miguel López, and
Manuel Tena-Sempere
December 1989,
Annales de pediatrie,
Violeta Heras, and
Juan Manuel Castellano, and
Daniela Fernandois, and
Inmaculada Velasco, and
Elvira Rodríguez-Vazquez, and
Juan Roa, and
Maria Jesus Vazquez, and
Francisco Ruiz-Pino, and
Matias Rubio, and
Rafael Pineda, and
Encarnacion Torres, and
Maria Soledad Avendaño, and
Alfonso Paredes, and
Leonor Pinilla, and
Denise Belsham, and
Carlos Diéguez, and
Francisco Gaytán, and
Nuria Casals, and
Miguel López, and
Manuel Tena-Sempere
January 1994,
Current therapy in endocrinology and metabolism,
Violeta Heras, and
Juan Manuel Castellano, and
Daniela Fernandois, and
Inmaculada Velasco, and
Elvira Rodríguez-Vazquez, and
Juan Roa, and
Maria Jesus Vazquez, and
Francisco Ruiz-Pino, and
Matias Rubio, and
Rafael Pineda, and
Encarnacion Torres, and
Maria Soledad Avendaño, and
Alfonso Paredes, and
Leonor Pinilla, and
Denise Belsham, and
Carlos Diéguez, and
Francisco Gaytán, and
Nuria Casals, and
Miguel López, and
Manuel Tena-Sempere
February 2009,
Current opinion in endocrinology, diabetes, and obesity,
Violeta Heras, and
Juan Manuel Castellano, and
Daniela Fernandois, and
Inmaculada Velasco, and
Elvira Rodríguez-Vazquez, and
Juan Roa, and
Maria Jesus Vazquez, and
Francisco Ruiz-Pino, and
Matias Rubio, and
Rafael Pineda, and
Encarnacion Torres, and
Maria Soledad Avendaño, and
Alfonso Paredes, and
Leonor Pinilla, and
Denise Belsham, and
Carlos Diéguez, and
Francisco Gaytán, and
Nuria Casals, and
Miguel López, and
Manuel Tena-Sempere
May 2006,
Expert opinion on investigational drugs,
Violeta Heras, and
Juan Manuel Castellano, and
Daniela Fernandois, and
Inmaculada Velasco, and
Elvira Rodríguez-Vazquez, and
Juan Roa, and
Maria Jesus Vazquez, and
Francisco Ruiz-Pino, and
Matias Rubio, and
Rafael Pineda, and
Encarnacion Torres, and
Maria Soledad Avendaño, and
Alfonso Paredes, and
Leonor Pinilla, and
Denise Belsham, and
Carlos Diéguez, and
Francisco Gaytán, and
Nuria Casals, and
Miguel López, and
Manuel Tena-Sempere
May 2019,
Journal of the Endocrine Society,
Violeta Heras, and
Juan Manuel Castellano, and
Daniela Fernandois, and
Inmaculada Velasco, and
Elvira Rodríguez-Vazquez, and
Juan Roa, and
Maria Jesus Vazquez, and
Francisco Ruiz-Pino, and
Matias Rubio, and
Rafael Pineda, and
Encarnacion Torres, and
Maria Soledad Avendaño, and
Alfonso Paredes, and
Leonor Pinilla, and
Denise Belsham, and
Carlos Diéguez, and
Francisco Gaytán, and
Nuria Casals, and
Miguel López, and
Manuel Tena-Sempere
March 2002,
Best practice & research. Clinical endocrinology & metabolism,
Violeta Heras, and
Juan Manuel Castellano, and
Daniela Fernandois, and
Inmaculada Velasco, and
Elvira Rodríguez-Vazquez, and
Juan Roa, and
Maria Jesus Vazquez, and
Francisco Ruiz-Pino, and
Matias Rubio, and
Rafael Pineda, and
Encarnacion Torres, and
Maria Soledad Avendaño, and
Alfonso Paredes, and
Leonor Pinilla, and
Denise Belsham, and
Carlos Diéguez, and
Francisco Gaytán, and
Nuria Casals, and
Miguel López, and
Manuel Tena-Sempere
August 2013,
The lancet. Diabetes & endocrinology,
