Programmed obesity in intrauterine growth-restricted newborns: modulation by newborn nutrition.
The degree of nutrient enhancement during the newborn period may modulate programming of appetite-regulating hormones, body composition, and propensity to adult obesity in intrauterine growth-restricted (IUGR) newborns. Pregnant rats received, from day 10 to term gestation and throughout lactation, ad libitum food (AdLib) or 50% food restriction (FR) to produce IUGR newborns. AdLib vs. FR offspring were studied at day 1, and, to create two distinct groups of newborn catch-up growth (immediate, delayed) among the IUGR newborns, cross-fostering techniques were employed. The four groups of pups at 3 wk were IUGR immediate catch-up growth (FR/AdLib), IUGR delayed catch-up growth (FR/FR), control (AdLib/AdLib), and lactation FR control (AdLib/FR). From 3 wk to 9 mo, all offspring had AdLib rat chow. Maternal FR during pregnancy resulted in IUGR pups (6.0 +/- 0.3 vs. 7.1 +/- 0.3 g, P < 0.01) with decreased leptin (0.66 +/- 0.03 vs. 1.63 +/- 0.12 ng/ml, P < 0.001) and increased ghrelin (0.43 +/- 0.03 vs. 0.26 +/- 0.02 ng/ml, P < 0.001). Maternal FR during lactation (FR/FR) further impaired IUGR offspring growth at 3 wk. However, by 9 mo, these pups attained normal body weight, percent body fat, and plasma leptin levels. Conversely, IUGR offspring nursed by AdLib dams (FR/AdLib) exhibited rapid catch-up growth at 3 wk and continued accelerated growth, resulting in increased weight, percent body fat, and plasma leptin levels. Thus the degree of newborn nutrient enhancement and timing of IUGR newborn catch-up growth may determine the programming of orexigenic hormones and offspring obesity.
Perinatal Research Laboratories, Department of Obstetrics and Gynecology, David-Geffen School of Medicine at University of California Los Angeles, Torrance, CA, USA. mdesai@obgyn.humc.edu
Mina
M
Desai
Dave
D
Gayle
Jooby
J
Babu
Michael G
MG
Ross
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001724:Birth Weight; D001823:Body Composition / Q000502:physiology; D001835:Body Weight; D005247:Feeding Behavior / Q000502:physiology; D005260:Female; D005317:Fetal Growth Retardation / Q000178:diet therapy / Q000503:physiopathology*; D005508:Food Deprivation; D006128:Growth / Q000502:physiology; D008297:Male; D009765:Obesity / Q000097:blood / Q000196:embryology* / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley