Caruso, V and Chen, H and Morris, MJ, Early hypothalamic FTO overexpression in response to maternal obesity--potential contribution to postweaning hyperphagia, PloS one, 6, (9) Article e25261. ISSN 1932-6203 (2011) [Refereed Article]
© 2011 Caruso et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. (Specific license not stated)
BACKGROUND: Intrauterine and postnatal overnutrition program hyperphagia, adiposity and glucose intolerance in offspring. Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene have been linked to increased risk of obesity. FTO is highly expressed in hypothalamic regions critical for energy balance and hyperphagic phenotypes were linked with FTO SNPs. As nutrition during fetal development can influence the expression of genes involved in metabolic function, we investigated the impact of maternal obesity on FTO.
METHODS: Female Sprague Dawley rats were exposed to chow or high fat diet (HFD) for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1 (PND1), some litters were adjusted to 3 pups (vs. 12 control) to induce postnatal overnutrition. At PND20, rats were weaned onto chow or HFD for 15 weeks. FTO mRNA expression in the hypothalamus and liver, as well as hepatic markers of lipid metabolism were measured.
RESULTS: At weaning, hypothalamic FTO mRNA expression was increased significantly in offspring of obese mothers and FTO was correlated with both visceral and epididymal fat mass (P<0.05); body weight approached significance (P = 0.07). Hepatic FTO and Fatty Acid Synthase mRNA expression were decreased by maternal obesity. At 18 weeks, FTO mRNA expression did not differ between groups; however body weight was significantly correlated with hypothalamic FTO. Postnatal HFD feeding significantly reduced hepatic Carnitine Palmitoyltransferase-1a but did not affect the expression of other hepatic markers investigated. FTO was not affected by chronic HFD feeding.
SIGNIFICANCE: Maternal obesity significantly impacted FTO expression in both hypothalamus and liver at weaning. Early overexpression of hypothalamic FTO correlated with increased adiposity and later food intake of siblings exposed to HFD suggesting upregulation of FTO may contribute to subsequent hyperphagia, in line with some human data. No effect of maternal obesity was observed on FTO in adulthood.
|Item Type:||Refereed Article|
|Keywords:||FTO, maternal obesity, hypothalamus, food intake|
|Research Division:||Biological Sciences|
|Research Group:||Biochemistry and cell biology|
|Research Field:||Analytical biochemistry|
|Objective Group:||Clinical health|
|Objective Field:||Diagnosis of human diseases and conditions|
|UTAS Author:||Caruso, V (Dr Vanni Caruso)|
|Web of Science® Times Cited:||19|
|Downloads:||141 View Download Statistics|
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