Intrauterine growth restriction induces central fat in the adult sheep — ASN Events

Intrauterine growth restriction induces central fat in the adult sheep (#38)

Hong Liu 1 2 , Damien Hunter 1 2 3 , Christopher G Schultz 4 , Miles De Blasio 1 2 5 , Karen L Kind 2 3 , Julie A Owens 1 2 , Kathryn L Gatford 1 2
  1. School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia
  2. Robinson Institute, University of Adelaide, Adelaide, SA, Australia
  3. School of Animal & Veterinary Sciences, University of Adelaide, Adelaide, SA, Australia
  4. Department of Nuclear Medicine & Bone Densitometry, Royal Adelaide Hospital, Adelaide, SA, Australia
  5. Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK

Background: In humans, low birthweight and accelerated neonatal growth, predict later obesity and metabolic disorders.  Whilst central adiposity (a predictor of later metabolic disease) develops by 4 years of age in intrauterine growth restricted (IUGR) children1, there are limited and conflicting findings regarding obesity and fat distribution in the IUGR adult2,3.  Similarly, IUGR sheep exhibit catch-up growth and increased visceral fat mass as juveniles4,5.  Whether this persists and alters adult fat mass distribution is undetermined. 

Methods: Placental restriction (PR) was induced by removing most uterine implantation sites of ewes before mating.  Weight and size were measured at birth and throughout life in control (CON; n=29), and PR (n=16) offspring.  Fat and lean tissue masses were assessed at ~43 weeks by dual x-ray absorptiometry for total body, upper (predominantly omental) and lower abdominal (includes perirenal and retroperitoneal depots) regions (Figure). 

Results: PR reduced birthweight (23%; CON: 6.09±0.34 kg; PR: 4.72±0.32 kg; p=0.02) but not adult weight.  In PR offspring, absolute (AGR) and fractional (FGR) neonatal growth rates (0 – 16 d) correlated with birthweight (AGR: r=0.603, p=0.013; FGR: r=-0.744, p=0.001; n=16).  In CON offspring, only AGR correlated with birthweight (AGR: r=0.654, p < 0.001; FGR: r=-0.356, p=0.058; n=29).  Total body fat (% body weight) was not correlated with birthweight (r=0.076, p=0.620, n=45), but, both upper abdominal fat (% total body fat; r=-0.401, p=0.006, n=45) and total body lean mass (r=0.446, p=0.002, n=45) correlated with birthweight. 

Conclusions: IUGR is associated with reduced lean tissue mass and unchanged overall adiposity in adult sheep, similar to that reported in humans, but with redistribution of fat centrally, possibly contributing to IUGR-associated adverse cardiovascular and metabolic health outcomes.


  1. Ibanez, L., et al., Early development of visceral fat excess after spontaneous catch-up growth in children with low birth weight. J Clin Endocrinol Metab, 2008. 93(3): p. 925-8.
  2. Yajnik, C.S., Obesity epidemic in India: intrauterine origins? Proc Nutr Soc, 2004. 63(3): p. 387-96.
  3. Rogers, I., The influence of birthweight and intrauterine environment on adiposity and fat distribution in later life. Int J Obes Relat Metab Disord, 2003. 27(7): p. 755-77.
  4. De Blasio, M.J., et al., Placental restriction of fetal growth reduces size at birth and alters postnatal growth, feeding activity, and adiposity in the young lamb. Am J Physiol Regul Integr Comp Physiol, 2007. 292(2): p. R875-86.
  5. Muhlhausler, B.S., et al., Birth weight and gender determine expression of adipogenic, lipogenic and adipokine genes in perirenal adipose tissue in the young adult sheep. Domest Anim Endocrinol, 2008. 35(1): p. 46-57.