Presented at the Neonatal Society 2007 Spring Meeting.
Anastasovska J1, So P-W2, Frost G3, Uthaya S4, Thomas EL1, Modi N4, Bell JD1
1 Molecular Imaging Group, MRC Clinical Sciences Centre, Hammersmith Hospital Campus, Imperial College London, UK
2 Biological Imaging Centre, MRC Clinical Sciences Centre, Imperial College London, UK
3 Department of Nutrition & Dietetics, University of Surrey, Guildford, UK
4 Division of Medicine, Chelsea & Westminster Hospital Campus, Imperial College London, UK
Introduction: Epidemiological research points to an association between undernutrition during early development and obesity and related disorders, such as the metabolic syndrome in adult life. Preterm infants are at major risk of antenatal and early postnatal undernutrition but long-term metabolic consequences are unknown. We have previously presented data to this Society showing that preterm babies develop increased intra-abdominal adiposity and intrahepatocellular lipid (IHCL) by term age-equivalent (1,2). Here, in an animal model we aim to investigate the effects of a low protein diet during gestation and lactation on body composition, IHCL and growth in adult offspring.
Methods: Pregnant C57/bl6 mice were maintained on a low (8%) protein diet or a control (20% protein) diet from the date mating was confirmed, and remained on these during the gestation (~19 days) and lactation periods (21 days). At 21 days of age, offspring from both diet groups (low protein n=6, control n=7) were weaned onto standard rodent chow for 12 weeks, during which body weights and lengths were measured weekly. At 15 weeks offspring were anaesthetised with an isoflurane-oxygen mix and scanned on a 4.7T Unity Inova MR scanner (Varian Inc, USA) using a birdcage whole body coil. Consecutive transverse MRI images of the whole mouse body were collected using a spin-echo sequence with parameters: TR 2.2 s, TE 20 ms, FOV 45 mm x 45 mm, matrix 256 x 192, 2 averages and 2 mm thick slices. Segmentation analysis was performed with SliceOmatic™ (Tomovision®) to provide volumes (and mass) of internal and subcutaneous adipose tissue deposits. Localised 1H MRS of the liver was performed using a PRESS sequence with TR 10 s, TE 9 ms and 64 averages following voxel (2x2x2 mm) placement by MRI. The spectra were analysed using MestRe-C (Santiago de Compostela, SPAIN) where an exponential line broadening of 1.5Hz was applied, prior to baseline correction and peak integration of the water and lipid peak. Data are presented as group mean ± SEM. This study complied with the Animals (Scientific Procedures) Act 1986.
Results: Offspring from the low protein group showed significantly higher IHCL ( low protein: 6.46 ± 0.95%; control: 3.37 ± 0.65%, p<0.05) and increased adiposity (low protein: 11.60 ± 2.34%, control: 6.47 ± 0.51%, p<0.05). Adipose tissue distribution was comparable between the two groups, although internal adipose tissue content was generally higher in the low protein offspring (p=0.25). There were no significant differences in body weight and length (female animal data only). The similarity in body weights despite increased adiposity is indicative that the increase in adipose tissue in the low protein offspring is accompanied by a decrease in lean body mass.
Conclusion: Low protein maternal nutrition during gestation and lactation leads to altered lipid metabolism and increased whole body adiposity in adult offspring. In this animal model the impact of maternal undernutrition has life-long consequences.
Acknowledgements: The authors acknowledge the use of the Biological Imaging Centre funded by the Wellcome Trust and Imperial College London and financial support from Numico Research.
References
1. Uthaya et al Pediatr Res 2005; 57:1-6
2. Thomas et al Earl Hum Dev 2005; 81:711-12