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Abnormalities of the somatotrophic axis in the obese agouti mouse

International Journal of Obesity volume 30, pages 430–438 (2006)Cite this article

Abstract

Objective:

Abnormalities of the melanocortin system produce obesity and increased linear growth. While the obesity phenotype is well characterised, the mechanism responsible for increased linear growth is unclear. The somatotrophic axis was studied in the obese agouti (Ay/a) mouse as a model of a perturbed melanocortin system.

Design:

Adult obese Ay/a mice were compared to age- and sex-matched wild-type (WT) controls. Weight and body length (nose–anus) were recorded. Plasma growth hormone (GH), insulin-like growth factor-I (IGFI), insulin and leptin were measured using radioimmunoassay. Since ghrelin is a potent GH secretagogue, plasma ghrelin, stomach ghrelin peptide and stomach ghrelin mRNA expression were studied. Hypothalamic periventricular (PeVN) somatostatin neurones and arcuate (Arc) neuropeptide Y (NPY) neurones inhibit the growth axis, whereas Arc growth hormone-releasing hormone (GHRH) neurones are stimulatory. Therefore, specific hypothalamic expression of somatostatin, NPY and GHRH was measured using quantitative in situ hybridisation.

Results:

Obese Ay/a mice were significantly heavier and longer than WT controls. Plasma IGFI concentrations were 30% greater in obese Ay/a mice. Obese Ay/a mice were hyperinsulinaemic and hyperleptinaemic, yet plasma ghrelin, and stomach ghrelin peptide and mRNA were significantly reduced. In obese Ay/a mice, PeVN somatostatin and Arc NPY mRNA expression were reduced by 50% compared to WT controls, whereas Arc GHRH mRNA expression was unchanged.

Conclusion:

Increased body length in adult obese Ay/a mice may result from reduced Arc NPY and PeVN somatostatin mRNA expression, which in turn, may increase plasma IGFI concentrations and upregulate the somatotrophic axis.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

Ay/a mouse:

agouti mouse

IGFI:

insulin-like growth factor-I

PeVN:

periventricular nucleus

Arc:

arcuate nucleus

GHRH:

growth hormone-releasing hormone

NPY:

neuropeptide Y

AgRP:

agouti-related protein

α-MSH:

alpha melancoyte-stimulating hormone

POMC:

pro-opiomelanocortin

CNS:

central nervous system

GH:

growth hormone

GHS-R:

growth hormone secretagogue receptor

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Acknowledgements

These data have been published in abstract form at the British Endocrine Society, 2004. We thank KG Murphy for helpful comments during the preparation of the manuscript. NMM is a Wellcome Trust Clinical Training Fellow. This work is supported by an MRC programme Grant G7811974 (Bloom, Ghatei and Small).

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Authors and Affiliations

  1. Department of Metabolic Medicine, Imperial College at Hammersmith Campus, London, UK

    N M Martin, M Patterson, A Sajedi, M A Ghatei, S R Bloom & C J Small

  2. Department of Molecular and Cellular Neuroscience, Division of Neuroendoscience and Psychological Medicine, Imperial College at Hammersmith Campus, London, UK

    P A Houston

  3. Division of Molecular Neuroendocrinology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK

    D F Carmignac

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  1. N M Martin
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  2. P A Houston
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Correspondence to S R Bloom.

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Martin, N., Houston, P., Patterson, M. et al. Abnormalities of the somatotrophic axis in the obese agouti mouse. Int J Obes 30, 430–438 (2006). https://doi.org/10.1038/sj.ijo.0803076

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