ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 7.3 | DOI: 10.1530/ey.16.7.3


To read the full abstract: Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):E10758–E10767.

The authors show for the first time that central AMP-activated protein kinase (AMPK), the major cellular energy sensor, interplays with Kiss1 to control puberty onset.

AMPK is an indispensable cellular energy sensor (1). Beside its ability to directly sense energy availability of the cell, hypothalamic AMPK is involved in the control of energy balance (1, 2). Fasting and orexigenic hormones activate AMPK, thereby inducing feeding, whereas refeeding and anorectic factors inhibit AMPK, resulting in suppression of food intake (1, 2).

The authors used intra-cerebro-ventricular injections of an AMPK activator as well as virogenetic overexpression of a constitutively active form of AMPKα and observed a profound delay of vaginal opening in female rats. They showed that AMPK is co-expressed in Kisspeptin neurons. While central administration of AMPK activator failed to modify Kiss1 mRNA in anteroventral periventricular nucleus neurons, Kiss1 expression in the arcuate nucleus was significantly blunted by the treatment. In addition, female mice with congenital ablation of AMPKα1 in Kiss1 neurons were partially protected from the delayed vaginal opening caused by undernutrition.

Thus, AMPK, which operates as a hypothalamic regulator of energy homeostasis, also plays a relevant role in Kiss1 neurons in the arcuate nucleus for the metabolic control of puberty and its inhibition by conditions of energy insufficiency. These data have a considerable translational potential, as early therapies with drugs known to activate AMPK, such as metformin, have been reported to delay menarche in low birth weight girls with precocious pubarche (3) even though the central versus peripheral mechanisms of such effects are still unknown.

References: 1. López M, Nogueiras R, Tena-Sempere M, Diéguez C. 2016 Hypothalamic AMPK: A canonical regulator of whole-body energy balance. Nat Rev Endocrinol. 12:421–432.

2. Xue B, Kahn BB 2006 AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues. J Physiol. 574:73–83.

3. Foretz M, Guigas B, Bertrand L, Pollak M, Viollet B. 2014 Metformin: From mechanisms of action to therapies. Cell Metab. 20:953–966.

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