title: Appetite regulatory mechanisms and food intake in mice are sensitive to mismatch in diets between pregnancy and postnatal periods.
abstract: Human and animal studies suggest that obesity in adulthood may have its origins partly during prenatal development. One of the underlying causes of obesity is the perturbation of hypothalamic mechanisms controlling appetite. We determined mRNA levels of genes that regulate appetite, namely neuropeptide Y (NPY), pro-opiomelanocortin (POMC) and the leptin receptor isoform Ob-Rb, in the hypothalamus of adult mouse offspring from pregnant dams fed a protein-restricted diet, and examined whether mismatched post-weaning high-fat diet altered further expression of these gene transcripts. Pregnant MF1 mice were fed either normal protein (C, 18% casein) or protein-restricted (PR, 9% casein) diet throughout pregnancy. Weaned offspring were fed to adulthood a high-fat (HF; 45% kcal fat) or standard chow (21% kcal fat) diet to generate the C/HF, C/C, PR/HF and PR/C groups. Food intake and body weight were monitored during this period. Hypothalamic tissues were collected at 16 weeks of age for analysis of gene expression by real time RT-PCR. All HF-fed offspring were observed to be heavier vs. C groups regardless of the maternal diet during pregnancy. In the PR/HF males, but not in females, daily energy intake was reduced by 20% vs. the PR/C group (p<0.001). In PR/HF males, hypothalamic mRNA levels were lower vs. the PR/C group for NPY (p<0.001) and Ob-Rb (p<0.05). POMC levels were similar in all groups. In females, mRNA levels for these transcripts were similar in all groups. Our results suggest that adaptive changes during prenatal development in response to maternal dietary manipulation may have long-term sex-specific consequences on the regulation of appetite and metabolism following post-weaning exposure to an energy-rich nutritional environment.
authors.affiliation: Institute of Developmental Sciences, Developmental Origins of Health and Disease Division, University of Southampton School of Medicine, Southampton General Hospital, Southampton, UK.
authors.forename: Dyan
authors.initials: D
authors.lastname: Sellayah
authors.forename: Kathleen
authors.initials: K
authors.lastname: Sek
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Anthony
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Watkins
authors.forename: Clive
authors.initials: C
authors.lastname: Osmond
authors.forename: Tom P
authors.initials: TP
authors.lastname: Fleming
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hanson
authors.forename: Felino R
authors.initials: FR
authors.lastname: Cagampang