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Hypothalamic Neuropeptide Expression of Juvenile and Middle-Aged Rats after Early Postnatal Food Restriction

Department of Pediatrics (F.R., H.A.D.-v.d.W.), Institute for Clinical and Experimental Neurosciences, Vrije Universiteit University Medical Center, 1081 HV Amsterdam, The Netherlands; and Rudolf Magnus Institute of Neuroscience (L.A.W.V., R.A.H.A.), Department of Neuroscience and Pharmacology, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands

Address all correspondence and requests for reprints to: Floor Remmers, M.Sc., Department of Pediatrics, Vrije Universiteit University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: floorremmers{at}hotmail.com.

Rats subjected to early postnatal food restriction (FR) show persistent changes in energy balance. The hypothalamus plays a major role in the regulation of energy balance. Therefore, we hypothesized that early postnatal food restriction induces developmental programming of hypothalamic gene expression of neuropeptides involved in this regulation. In the hypothalamus of juvenile and middle-aged rats that were raised in control (10 pups) or FR litters (20 pups), gene expression was investigated for neuropeptide Y (NPY), agouti-related protein (AgRP), proopiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART) in the arcuate nucleus (ARC); CRH and TRH in the paraventricular nucleus; and melanin-concentrating hormone (MCH) and orexin in the lateral hypothalamic area. Early postnatal FR acutely and persistently reduced body size. Juvenile FR rats had significantly reduced CART gene expression and increased MCH expression. In middle-aged FR rats, POMC and CART mRNA levels were significantly reduced. The ratio between expression of the ARC orexigenic peptides (NPY and AgRP) and anorexigenic peptides (POMC and CART) was increased in juvenile, but not in middle-aged, FR rats. These results suggest that in neonatal rats, FR already triggers the ARC, and to a lesser extent the lateral hypothalamic area, but not the paraventricular nucleus, to increase expression of orexigenic relative to anorexigenic peptides. In addition, with enduring small body size and normalized hypothalamic gene expression, the adult FR rats appeared to have accepted this smaller body size as normal. This suggests that the body weight set-point was differently programmed in animals with early postnatal FR.