Stimulation of GHRH Neuron Axon Growth by Leptin and Impact of Nutrition during Suckling in Mice

Author:

Decourtye-Espiard Lyvianne1ORCID,Clemessy Maud1,Leneuve Patricia1,Mire Erik1,Ledent Tatiana1ORCID,Le Bouc Yves12,Kappeler Laurent12ORCID

Affiliation:

1. INSERM, Centre de Recherche St-Antoine, Sorbonne Université, F-75012 Paris, France

2. IHU-ICAN Institute of Cardiometabolism and Nutrition, F-75013 Paris, France

Abstract

Nutrition during the early postnatal period can program the growth trajectory and adult size. Nutritionally regulated hormones are strongly suspected to be involved in this physiological regulation. Linear growth during the postnatal period is regulated by the neuroendocrine somatotropic axis, whose development is first controlled by GHRH neurons of the hypothalamus. Leptin that is secreted by adipocytes in proportion to fat mass is one of the most widely studied nutritional factors, with a programming effect in the hypothalamus. However, it remains unclear whether leptin stimulates the development of GHRH neurons directly. Using a Ghrh-eGFP mouse model, we show here that leptin can directly stimulate the axonal growth of GHRH neurons in vitro in arcuate explant cultures. Moreover, GHRH neurons in arcuate explants harvested from underfed pups were insensitive to the induction of axonal growth by leptin, whereas AgRP neurons in these explants were responsive to leptin treatment. This insensitivity was associated with altered activating capacities of the three JAK2, AKT and ERK signaling pathways. These results suggest that leptin may be a direct effector of linear growth programming by nutrition, and that the GHRH neuronal subpopulation may display a specific response to leptin in cases of underfeeding.

Funder

Institut National de la Santé et de la Recherche Médicale

Sorbonne Université

Institute of Cardiometabolism and Nutrition

Sandoz-France Laboratories

Premup Foundation

Publisher

MDPI AG

Subject

Food Science,Nutrition and Dietetics

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