Presented at the Neonatal Society 2005 Autumn Meeting.
Mostyn A1, Patel HN1, Litten JC2, Perkins KS2, Corson AM2, Symonds ME1, Clarke L2
1 Centre for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, NG7 2UH, UK
2 Department of Agricultural Sciences, Imperial College London Wye Campus, Wye, Ashford, Kent, TN25 5AH, UK
Epidemiology has shown that infants of low birth weight show poor neonatal growth and increased susceptibility to adult diseases such as diabetes and obesity in later life. PPARγ is a transcription factor involved in the regulation of adipose tissue development and lipid metabolism and is implicated in type 2 diabetes. Pigs provide an ideal model to examine the influence of size at birth due to the natural variance in piglet weight within a litter, impairment of glucose tolerance and increased body fat has been observed in low birth weight offspring in adulthood (3,4). This study examined whether birth weight influences the expression of PPAR and the extent of lipid storage during early life in the pig.
Piglets from 11 litters were ranked according to body weight at birth and 3 animals from each were assigned to small (SFD n=11), normal (NFD n=11) or large for dates (LFD n=11) groups. Piglets were euthanased with an overdose of barbiturate (100 mg kg-1 pentobarbital sodium: Euthatal) on days 7 (n=15) and 14 (n=18) to obtain AT. Adipose tissue triacylglyceride (TAG) content was measured using a commercial kit following extraction by the Folch method. PPARγ expression in AT was measured using RT-PCR as described previously (1). GLM analysis was carried out to investigate statistical differences; results are presented as means ± standard errors.
TAG content of adipose tissue was not found to be significantly affected by birth weight (e.g. day 7; SFD, 141.2±87.5; NFD, 266.6±43.2; LFD, 237.8±59.3 mg.dL-1 although TAG content more than doubled over the second week of life in the SFD piglets, compared to an increase of only 10-20% in the NFD and LFD group (SFD day 7; 141.2±87.5; SFD day 14; 368.9±12.7 mg.dL-1 (P=0.06)). PPARγ mRNA abundance was similar between NFD and SFD piglets, but was significantly lower in LFD compared to NFD piglets on day 14 (NFD; 161.1±15.0; LFD 121.1±6.7 (P<0.05) arbitrary units).
Enhanced TAG storage during early development in SFD piglets suggests that these piglets are laying down increased lipid reserves. It is possible that these increased reserves will lead to impaired glucose tolerance and obesity in later life. PPARγ mRNA expression in these piglets was unaltered, suggesting impaired ability to regulate an influx of lipid. In view of the potentially deleterious long term consequences of accelerated growth in the smaller infants; this may be one factor putting these individuals at increased risk of later metabolic disease.
References
1. Mostyn A, Litten JC, Perkins KS, Alves-Guerra M, Pecqueur C, Miroux B, Symonds ME, and Clarke L. J Endocrinol 183: 121-131, 2004.
2. Mostyn A, Litten JC, Perkins KS, Euden PJ, Corson AM, Symonds ME, and Clarke L. Am J Physiol 288: R1536 – R1542, 2005.
3. Poore KR and Fowden AL. Diabetologia 45: 1247-1254, 2002.
4. Poore KR and Fowden AL. J Physiol 558: 295-304, 2004.