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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Early Undernutrition Leads to Long-Lasting Reductions in Body Weight and Adiposity Whereas Increased Intake Increases Cardiac Fibrosis in Male Rats^1,2

³ Department of Pharmacology, University of Melbourne, Parkville, 3010, Australia; ⁴ Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800, Victoria, Australia; ⁵ Department of Medicine, University of Melbourne, Heidelberg Repatriation Hospital, Heidelberg Heights, 3081, Victoria, Australia; and ⁶ Department of Pharmacology, School of Medical Sciences, University of New South Wales, 2052, New South Wales, Australia

Previous studies suggest that both overfeeding and undernutrition during development increase the risk of obesity and hypertension in adulthood. In this study, we examined both short- (24 d) and long- (16 wk) term effects of early postnatal over- and underfeeding in rats on body weight, body composition, plasma hormones, adiposity markers, and hypothalamic neuropeptide Y content. Cardiovascular changes were also examined by measuring blood pressure and cardiac fibrosis. Rats raised in litters of 3, 12, or 18 pups per mother were used to model early onset overfeeding, control, and underfeeding, respectively. At 24 d of age, pups raised in small litters (SL) were 10% heavier than pups from normal litters, accompanied by increased organ mass and fat mass, elevated plasma leptin, corticosterone, and uncoupling protein-1 mRNA in brown adipose tissue. On the other hand, pups raised in large litters were 17% lighter with no significant changes in plasma leptin. Overfeeding during the first 3 wk of life led to increased plasma leptin concentration in adulthood, whereas underfed rats remained significantly lighter throughout the study, with no evidence of catch-up growth. Rats raised in SL were more susceptible to developing cardiac fibrosis with a 22% increase in collagen deposition compared with control rats at 16 wk of age (P < 0.05). This was independent of any changes in blood pressure. This study demonstrates that nutritional changes early in postnatal development can have long-lasting effects on body weight, adiposity, and some mediators involved in energy homeostasis and can also lead to structural changes in the heart in adulthood. This highlights the importance of identifying potential early life risk factors involved in the modulation of childhood nutrition.

^* To whom correspondence should be addressed. E-mail: m.morris{at}unsw.edu.au.

Manuscript received 25 January 2008. Initial review completed 27 February 2008. Revision accepted 13 June 2008.

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