Pulsatile Growth Hormone Secretion is Inversely Correlated to Adiposity and Circulating Levels of Leptin in Mice — ASN Events

Pulsatile Growth Hormone Secretion is Inversely Correlated to Adiposity and Circulating Levels of Leptin in Mice (#41)

T Y Xie 1 , F J Steyn 1 , L Huang 1 , S T Ngo 1 , J D Veldhuis 2 , C Chen 1
  1. School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia
  2. Ghrelin Research Group, Translational Research Institute - Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia

The decline in overall spontaneous and stimulated growth hormone (GH) secretion in overweight and obese individuals is well established1 . While impaired GH secretion is usually observed alongside increased adiposity, some debate exists as to whether impaired GH secretion contributes to or is a consequence of increased adiposity. To this extend, mouse models may provide essential information to elucidate the relationship between adiposity and GH secretion.
To further assess the relationship between adiposity and GH secretion in the mouse, we first characterized the impact of obesity on pulsatile GH secretion in C57BL/6J mice following 8 weeks of high fat feeding. Second to this we assessed the correlation between body weight, adiposity, circulating levels of leptin and free fatty acids (FFA) in healthy control C57Bl/6J mice. Subsequently, the correlation between overall pulsatile GH secretion and adiposity was evaluated. For measures of pulsatile GH secretion, tail-tip whole blood samples (4μl) were collected over a 6hr period at 10min intervals starting at 0700h and assayed for GH2 . Pulsatile GH secretion was analyzed by deconvolution analysis following guidelines established previously3 .
Our observations confirm a significant reduction in overall GH secretion in mice following dietary induced weight gain. This occurred alongside an increase in adiposity and the corresponding increase in circulating levels of leptin. Assessment of the relationship between pulsatile GH secretion and adiposity in healthy control mice demonstrate a significant negative correlation between GH parameters (total, pulsatile GH secretion and mass of GH secreted per burst (MPP)) and adiposity, as well as circulating levels of leptin. Observations further demonstrate the close inverse relationship between adiposity and pulsatile GH secretion in mammals.

This work is supported by NHMRC and The University of Queensland.

  1. (1) J.D. Veldhuis, A Iranmanesh et al. (1991) Dual defects in Pulsatile Growth Hormone Secretion and Clearance Subserve the Hyposomatotropism of Obesity in Man. Journal of Clinical Endocrinology and Metabolism. 72 (1): 51-59.
  2. (2) F.J. Steyn, L. Huang et al. (2011) Development of a method for the determination of pulsatile growth hormone secretion in mice. Endocrinology. 152 (8): 3165-71.
  3. (3) F.J. Steyn, S.T. Ngo et al. (2012) Impairments to the GH-IGF1 axis in hSOD1G93A mice give insight into possible mechanisms of GH dysregulation in patients with Amyotrophic Lateral Sclerosis. Endocrinology. doi:10.1210/en.2011-2171.