RT Journal Article
T1 Novel mechanisms for the metabolic control of puberty: implications for pubertal alterations in early-onset obesity and malnutrition.
A1 Vazquez, M J
A1 Velasco, I
A1 Tena-Sempere, M
K1 AMPK
K1 GnRH
K1 Kiss1
K1 NKB
K1 Environmental cues
K1 Kisspeptins
K1 mTOR
K1 Obesity
K1 Puberty
K1 Sirtuins
K1 Undernutrition
AB Puberty is driven by sophisticated neuroendocrine networks that timely activate the brain centers governing the reproductive axis. The timing of puberty is genetically determined; yet, puberty is also sensitive to numerous internal and external cues, among which metabolic/nutritional signals are especially prominent. Compelling epidemiological evidence suggests that alterations of the age of puberty are becoming more frequent; the underlying mechanisms remain largely unknown, but the escalating prevalence of obesity and other metabolic/feeding disorders is possibly a major contributing factor. This phenomenon may have clinical implications, since alterations in pubertal timing have been associated to adverse health outcomes, including higher risk of earlier all-cause mortality. This urges for a better understanding of the neurohormonal basis of normal puberty and its deviations. Compelling evidence has recently documented the master role of hypothalamic neurons producing kisspeptins, encoded by Kiss1, in the neuroendocrine pathways controlling puberty. Kiss1 neurons seemingly participate in transmitting the regulatory actions of metabolic cues on pubertal maturation. Key cellular metabolic sensors, as the mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK) and the fuel-sensing deacetylase, SIRT1, have been recently shown to participate also in the metabolic modulation of puberty. Recently, we have documented that AMPK and SIRT1 operate as major molecular effectors for the metabolic control of Kiss1 neurons and, thereby, puberty onset. Alterations of these molecular pathways may contribute to the perturbation of pubertal timing linked to conditions of metabolic stress in humans, such as subnutrition or obesity and might become druggable targets for better management of pubertal disorders.
PB BioScientifica
YR 2019
FD 2019-06-10
LK http://hdl.handle.net/10668/14099
UL http://hdl.handle.net/10668/14099
LA en
NO Vazquez MJ, Velasco I, Tena-Sempere M. Novel mechanisms for the metabolic control of puberty: implications for pubertal alterations in early-onset obesity and malnutrition. J Endocrinol. 2019 Aug;242(2):R51-R65
NO The work from the authors’ laboratory summarized  in this article was supported by grants BFU2014-57581-P and BFU2017-83934-P (Ministerio de Economía y Competitividad, Spain; co-funded with EU funds from FEDER Program); project PIE14-00005 (Flexi-Met, Instituto de Salud Carlos III, Ministerio de Sanidad, Spain); Projects P08-CVI-03788 and P12-FQM-01943 (Junta de Andalucía, Spain); and EU research contract DEER FP7-ENV-2007-1. CIBER is an initiative of Instituto de Salud Carlos III (Ministerio de Sanidad, Spain).
DS RISalud
RD Apr 17, 2025