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Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression

S P Sebert, M A Hyatt, L L Y Chan, M Yiallourides, H P Fainberg, N Patel, D Sharkey, T Stephenson, S M Rhind, R C Bell, H Budge, D S Gardner, M E Symonds, Melanie Healy

Reproduction, Volume: 139, Issue: 1, Pages: 265 - 274

Swansea University Author: Melanie Healy

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DOI (Published version): 10.1530/REP-09-0173

Abstract

The recent discovery of an association between body composition, energy intake and the fat mass and obesity-associated (FTO) gene represents a promising new therapeutic target in obesity prevention. In a well, pre-established large animal model, we investigated the regulation of FTO gene expression...

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Published in: Reproduction
ISSN: 1470-1626 1741-7899
Published: 2009
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URI: https://cronfa.swan.ac.uk/Record/cronfa12193
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spelling 2011-10-01T00:00:00.0000000 v2 12193 2012-07-20 Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression 4654b4128fb21d68f98e2abc8538b45a Melanie Healy Melanie Healy true false 2012-07-20 PHAR The recent discovery of an association between body composition, energy intake and the fat mass and obesity-associated (FTO) gene represents a promising new therapeutic target in obesity prevention. In a well, pre-established large animal model, we investigated the regulation of FTO gene expression under conditions either leading to obesity or increased risk of obesity related disorders: i) a sedentary 'Western' lifestyle and ii) prenatal exposure to nutrient restriction. Pregnant sheep were either fed to fully meet their nutritional requirements throughout gestation or 50% of this amount from early-to-mid gestation. Following weaning, offspring were either made obese through exposure to a sedentary obesogenic environment or remained lean. A significant positive relationship between placental FTO gene expression and fetal weight was found at 110 days gestation. In both the newborn and adult offspring, the hypothalamus was the major site of FTO gene expression. Hypothalamic FTO gene expression was upregulated by obesity and was further increased by prenatal nutrient restriction. Importantly, we found a strong negative relationship between the hypothalamic FTO gene expression and food intake in lean animals only that may imply FTO as a novel controller of energy intake. In contrast, FTO gene expression in the heart was downregulated in obese offspring born to nutrient restricted mothers. In addition, FTO gene expression was unaffected by obesity or prenatal diet in insulin-dependent tissues, where it changed with age possibly reflecting adaptations in cellular energetic activity. These findings extend information gained from human epidemiology and provide new insights into the regulation of in vivo energy metabolism to prevent obesity. Journal Article Reproduction 139 1 265 274 1470-1626 1741-7899 30 9 2009 2009-09-30 10.1530/REP-09-0173 http://www.reproduction-online.org/content/139/1/265.long COLLEGE NANME Pharmacy COLLEGE CODE PHAR Swansea University 2011-10-01T00:00:00.0000000 2012-07-20T11:41:25.4094154 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine S P Sebert 1 M A Hyatt 2 L L Y Chan 3 M Yiallourides 4 H P Fainberg 5 N Patel 6 D Sharkey 7 T Stephenson 8 S M Rhind 9 R C Bell 10 H Budge 11 D S Gardner 12 M E Symonds 13 Melanie Healy 14
title Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression
spellingShingle Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression
Melanie Healy
title_short Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression
title_full Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression
title_fullStr Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression
title_full_unstemmed Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression
title_sort Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression
author_id_str_mv 4654b4128fb21d68f98e2abc8538b45a
author_id_fullname_str_mv 4654b4128fb21d68f98e2abc8538b45a_***_Melanie Healy
author Melanie Healy
author2 S P Sebert
M A Hyatt
L L Y Chan
M Yiallourides
H P Fainberg
N Patel
D Sharkey
T Stephenson
S M Rhind
R C Bell
H Budge
D S Gardner
M E Symonds
Melanie Healy
format Journal article
container_title Reproduction
container_volume 139
container_issue 1
container_start_page 265
publishDate 2009
institution Swansea University
issn 1470-1626
1741-7899
doi_str_mv 10.1530/REP-09-0173
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
url http://www.reproduction-online.org/content/139/1/265.long
document_store_str 0
active_str 0
description The recent discovery of an association between body composition, energy intake and the fat mass and obesity-associated (FTO) gene represents a promising new therapeutic target in obesity prevention. In a well, pre-established large animal model, we investigated the regulation of FTO gene expression under conditions either leading to obesity or increased risk of obesity related disorders: i) a sedentary 'Western' lifestyle and ii) prenatal exposure to nutrient restriction. Pregnant sheep were either fed to fully meet their nutritional requirements throughout gestation or 50% of this amount from early-to-mid gestation. Following weaning, offspring were either made obese through exposure to a sedentary obesogenic environment or remained lean. A significant positive relationship between placental FTO gene expression and fetal weight was found at 110 days gestation. In both the newborn and adult offspring, the hypothalamus was the major site of FTO gene expression. Hypothalamic FTO gene expression was upregulated by obesity and was further increased by prenatal nutrient restriction. Importantly, we found a strong negative relationship between the hypothalamic FTO gene expression and food intake in lean animals only that may imply FTO as a novel controller of energy intake. In contrast, FTO gene expression in the heart was downregulated in obese offspring born to nutrient restricted mothers. In addition, FTO gene expression was unaffected by obesity or prenatal diet in insulin-dependent tissues, where it changed with age possibly reflecting adaptations in cellular energetic activity. These findings extend information gained from human epidemiology and provide new insights into the regulation of in vivo energy metabolism to prevent obesity.
published_date 2009-09-30T03:14:06Z
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score 11.013148

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