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Department of Biochemistry, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York at Buffalo, 140 Farber Hall, 3435 Main Street, Buffalo, New York 14214, USA¹ Department of Pediatrics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA² Department of Medicine, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214, USA³ Diabetes and Endocrinology Center of Western New York, Kaleida Health, Buffalo, New York 14209, USA

(Correspondence should be addressed to M S Patel; Email: mspatel{at}buffalo.edu)

^* (M Srinivasan and P Mitrani contributed equally to this work)

Newborn rat pups artificially raised on a high-carbohydrate (HC) milk formula are chronically hyperinsulinemic and develop adult-onset obesity. As HC rats display aberrations in body weight regulation, hypothalamic adaptations predisposing to obesity have been investigated in this study. The artificial rearing of neonatal rat pups on the HC milk formula resulted in significant increases in the mRNA levels of neuropeptide Y, agouti-related polypeptide, and galanin in the hypothalamus of 12-day-old HC rats. Simultaneously, decreases in the mRNA levels of POMC, melanocortin receptor-4, cocaine- and amphetamine-regulated transcript, and corticotrophin-releasing factor were observed in the hypothalamus of these rats. These changes persisted in 100-day-old HC rats despite weaning onto a rodent diet on postnatal day 24. Marked hyperphagia and increased body weight gain were observed in the post-weaning period. The mRNA levels and protein content of insulin receptor β (IR-β) and leptin receptor (long form) showed significant decreases in the hypothalamus of both 12- and 100-day-old HC rats. Further investigation of insulin signaling in the hypothalamus of HC rats indicated significant decreases in the proximal signaling components (insulin receptor substrate proteins 1 and 2 and phosphotidylinositol 3-kinase) in 100-day-old HC rats. These results suggest that hypothalamic neuropeptides respond to the increased carbohydrate availability with associated hormonal alterations during the period of dietary modulation and that these adaptations by persisting in the post-weaning period predispose the HC rats for adult-onset obesity.

This article has been cited by other articles:

				M. Srinivasan, C. Dodds, H. Ghanim, T. Gao, P. J. Ross, R. W. Browne, P. Dandona, and M. S. Patel Maternal obesity and fetal programming: effects of a high-carbohydrate nutritional modification in the immediate postnatal life of female rats Am J Physiol Endocrinol Metab, October 1, 2008; 295(4): E895 - E903. [Abstract] [Full Text] [PDF]