Novel mechanisms for the metabolic control of puberty: implications for pubertal alterations in early-onset obesity and malnutrition.

摘要: Puberty is driven by sophisticated neuroendocrine networks that timely activate the brain centers governing reproductive axis. The timing of puberty genetically determined; yet, also sensitive to numerous internal and external cues, among which metabolic/nutritional signals are especially prominent. Compelling epidemiological evidence suggests alterations age becoming more frequent; underlying mechanisms remain largely unknown, but escalating prevalence obesity other metabolic/feeding disorders possibly a major contributing factor. This phenomenon may have clinical implications, since in pubertal been associated adverse health outcomes, including higher risk earlier all-cause mortality. urges for better understanding neurohormonal basis normal its deviations. has recently documented master role hypothalamic neurons producing kisspeptins, encoded Kiss1, pathways controlling puberty. Kiss1 seemingly participate transmitting regulatory actions metabolic cues on maturation. Key cellular sensors, as mammalian target rapamycin (mTOR), AMP-activated protein kinase (AMPK) fuel-sensing deacetylase, SIRT1, shown modulation Recently, we AMPK SIRT1 operate molecular effectors control and, thereby, onset. Alterations these contribute perturbation linked conditions stress humans, such subnutrition or might become druggable targets management disorders.