title: Maternal nutritional history modulates the hepatic IGF-IGFBP axis in adult male rat offspring.
abstract: Alterations in early life nutrition lead to an increased risk of obesity and metabolic syndrome in offspring. We have shown that both relative maternal undernutrition (UN) and maternal obesity result in metabolic derangements in offspring, independent of the postnatal dietary environment. Since insulin-like growth factor binding protein 2 (IGFBP2) has been shown to be independently associated with obesity and diabetes risk, we examined the IGF-IGFBP axis in male rat offspring following either maternal UN or maternal obesity to explain possible common pathways in the development of metabolic disorders. Wistar rats were time-mated and fed either a control diet (CONT), 50 % of CONT (UN) or a high-fat (HF) diet throughout pregnancy. Male offspring were weaned onto a standard chow diet and blood and tissues were collected at postnatal day 160. Plasma and hepatic tissue samples were analysed for key players in the IGF-IGFBP system. Both maternal UN and HF resulted in increased fat mass, hyperinsulinemia, hyperleptinemia and altered blood lipid profiles in offspring compared to CONT. Circulating IGF-1 and IGFBP3 levels and hepatic mRNA expression of IGFBP1 and IGFBP2 were significantly decreased in UN and HF offspring compared to CONT. DNA methylation of the IGFBP2 promotor region was similar between maternal dietary groups. Although chaperone gene heat-shock protein 90 and hepatic IGFBP1 were significantly correlated in CONT offspring this effect was absent in both UN and HF offspring. In conclusion, this study is one of the first to directly compare two experimental models of developmental programming representing both ends of the maternal dietary spectrum. Our data suggest that two disparate nutritional models that elicit similar adverse metabolic phenotypes in offspring are characterised by common alterations in the IGF-IGFBP pathway.
authors: Liggins Institute and Gravida: National Centre for Growth and Development, University of Auckland, Auckland, New Zealand.
authors: Timothy
authors: T
authors: Smith
authors: Deborah M
authors: DM
authors: Sloboda
authors: Richard
authors: R
authors: Saffery
authors: Eric
authors: E
authors: Joo
authors: Mark H
authors: MH
authors: Vickers
mesh_terms: D000818:Animals; D001724:Birth Weight; D001823:Body Composition; D001835:Body Weight; D019175:DNA Methylation; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D015870:Gene Expression; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D044342:Malnutrition / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D011247:Pregnancy; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D012313:RNA; D007334:Insulin-Like Growth Factor I
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