Poster Presentation The International Congress of Neuroendocrinology 2014

Exploration of the GH/IGF-1 axis, appetite and metabolism in GHS-R deficient mice (#312)

Alexandra Labarthe 1 , Rim Hassouna 1 , Philippe Zizzari 1 , Oriane Fiquet 1 , Emil Egecioglu 2 , Mohammad Bohlooly-Y 3 , Jacques Epelbaum 1 , Virginie Tolle 1
  1. Center for Psychiatry and Neurosciences, University Paris Descartes, UMR894 INSERM, Paris, France
  2. Section for Gastroenterology, Diabetes and Endocrinology, Institution of Experimental Medical Sciences, Lund University, Lund, Sweden
  3. RAD-Transgenic, Discovery Science, AstraZeneca R&D, Mölndal, Sweden

The gut hormone Ghrelin is the endogenous ligand of the Growth Hormone Secretagogue Receptor 1a (GHSR-1a). GHS-R-1a deficient mice maintain a lean phenotype when ageing and are resistant to diet-induced obesity, mainly due to increased energy expenditure but they are not hypophagic. To date, the consequence of GHS-R1a ablation on the activity of the GH/IGF-1 axis during ageing has never been explored. In the present study, we measured body weight, linear growth, adipose tissue, feeding and locomotor activities and parameters of the GH/IGF-1 axis in young (2-3 months) and middle aged (8-12 months) GHS-R1a deficient mice (*) (GHS-R KO) and wild-type C57BL/6 littermates (WT). While WT mice gained weight with ageing, GHS-R1a KO mice maintained a lower body weight (26% increase in WT versus 12% increase in KO between 3 and 8 months old). At 12 months, all fat deposits were significantly reduced in GHS-R1a KO compared to WT (40% for visceral, 50% for subcutaneous, 53% for gonadal and 56% for peri-renal, respectively). Increased home-cage activity, but not hypophagia, was observed and may contribute to the leaner phenotype in KO. Pituitary GH content was tripled in 12 months old KO mice, which may reflect a reduced ability to release GH. In order to evaluate whether GH secretion was altered in KO, ultradian variations were assessed by collecting repeated blood samples from tail bleeding every 10 minutes over a period of 6 hours in 3 and 12 months old animals. To date, after deconvolution analyses of GH secretory profiles, the mean amplitude of GH pulses was similar between WT and KO mice at both ages. As increased adiposity correlates with suppression of pulsatile GH secretion, lack of GH pulses alteration in KO mice may be related to reduced adiposity and/or increased activity.

*GHS-R1a deficient mice were provided by AstraZeneca.