Endocrine Abstracts (2009) 19 P200

The influence of birth weight on glucocorticoid receptor (GR) and peroxisome proliferator activated receptor (PPAR)[alpha] gene expression and lipid content in liver from neonatal pigs

T Kwok1, K Almond1, J Litten-Brown2, A Corson3, L Clarke3, M Symonds1 & A Mostyn1

1Institute of Clinical Research, Centre for Reproduction and Early Life, University of Nottingham, Nottingham, UK; 2School of Agriculture, Policy & Development, University of Reading, Reading, UK; 3Faculty of Natural Sciences, Imperial College London, London, UK.

Background: Birth weight has important consequences for later health, including the development of the metabolic syndrome. Tissue sensitivity to cortisol is regulated, in part, by the GR and alterations in its expression occur in obesity and type 2 diabetes. Low birth weight is associated with increased fat mass and down-regulation of PPARα, in skeletal muscle of neonatal pigs.

Objectives: To examine whether birth weight influences GR or PPARα mRNA expression and lipid content in liver of neonatal pigs.

Methods: Piglets from eleven separate litters were ranked according to birth weight and three from each litter were assigned to small (S), normal (N) or large (L) groups. Animals were humanely euthanased on day 7 (n=15) or 14 (n=18) of age and the liver sampled. Gene expression was quantified by real-time PCR. Lipid content was assessed using the Folch method followed by colourometric analysis of triglyceride content.

Results: S piglets had proportionately heavier livers compared to N on day 7 (S, 4.03±0.24; N, 3.34±0.11% body weight (P<0.05)). On day 14, S pigs had higher expression of PPARα than N pigs (S, 1.53±0.19; N 1.0±0.24 fold change (P<0.05)). Liver lipid content was negatively related to liver % weight in S pigs on day 7 (P<0.05). A positive relationship between GR and PPARα expression was observed in N liver on both days (P<0.05). A negative relationship between liver % weight and triglyceride content was observed in S liver on day 7 (P<0.05).

Conclusion: Increased PPARα expression in S pigs may be a compensatory response to cope with the comparatively higher metabolic demands during early life. Further investigations will determine whether these changes continue into later life.

TCK was supported by a Society For Endocrinology Summer Studentship.

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