title: Maternal obesity induced by diet in rats permanently influences central processes regulating food intake in offspring.
abstract: Hypothalamic systems which regulate appetite may be permanently modified during early development. We have previously reported hyperphagia and increased adiposity in the adult offspring of rodents fed an obesogenic diet prior to and throughout pregnancy and lactation. We now report that offspring of obese (OffOb) rats display an amplified and prolonged neonatal leptin surge, which is accompanied by elevated leptin mRNA expression in their abdominal white adipose tissue. At postnatal Day 30, before the onset of hyperphagia in these animals, serum leptin is normal, but leptin-induced appetite suppression and phosphorylation of STAT3 in the arcuate nucleus (ARC) are attenuated; the level of AgRP-immunoreactivity in the hypothalamic paraventricular nucleus (PVH), which derives from neurones in the ARC and is developmentally dependent on leptin, is also diminished. We hypothesise that prolonged release of abnormally high levels of leptin by neonatal OffOb rats leads to leptin resistance and permanently affects hypothalamic functions involving the ARC and PVH. Such effects may underlie the developmental programming of hyperphagia and obesity in these rats.
authors.affiliation: Division of Reproduction and Endocrinology, King's College London, London, UK.
authors.forename: Shona L
authors.initials: SL
authors.lastname: Kirk
authors.forename: Anne-Maj
authors.initials: AM
authors.lastname: Samuelsson
authors.forename: Marco
authors.initials: M
authors.lastname: Argenton
authors.forename: Hannah
authors.initials: H
authors.lastname: Dhonye
authors.forename: Theodosis
authors.initials: T
authors.lastname: Kalamatianos
authors.forename: Lucilla
authors.initials: L
authors.lastname: Poston
authors.forename: Paul D
authors.initials: PD
authors.lastname: Taylor
authors.forename: Clive W
authors.initials: CW
authors.lastname: Coen
mesh_terms: D000821:Animal Feed; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D004032:Diet; D004435:Eating; D005247:Feeding Behavior; D005260:Female; D005502:Food; D006963:Hyperphagia / Q000473:pathology; D007031:Hypothalamus / Q000473:pathology; D020738:Leptin / Q000378:metabolism; D009035:Mothers; D009765:Obesity / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D020738:Leptin; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat