title: A high-carbohydrate diet in the immediate postnatal life of rats induces adaptations predisposing to adult-onset obesity.
abstract: 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 beta (IR-beta) 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.
authors.affiliation: 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, USA.
authors.forename: Malathi
authors.initials: M
authors.lastname: Srinivasan
authors.forename: Paul
authors.initials: P
authors.lastname: Mitrani
authors.forename: Gigani
authors.initials: G
authors.lastname: Sadhanandan
authors.forename: Catherine
authors.initials: C
authors.lastname: Dodds
authors.forename: Suhad
authors.initials: S
authors.lastname: Shbeir-ElDika
authors.forename: Shanthie
authors.initials: S
authors.lastname: Thamotharan
authors.forename: Hussam
authors.initials: H
authors.lastname: Ghanim
authors.forename: Paresh
authors.initials: P
authors.lastname: Dandona
authors.forename: Sherin U
authors.initials: SU
authors.lastname: Devaskar
authors.forename: Mulchand S
authors.initials: MS
authors.lastname: Patel
mesh_terms: D054369:Agouti-Related Protein / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D005260:Female; D007031:Hypothalamus / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics; D009765:Obesity / Q000209:etiology*; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism
chemical_list: D054369:Agouti-Related Protein; D004040:Dietary Carbohydrates; D020738:Leptin; D009478:Neuropeptide Y; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D011972:Receptor, Insulin