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Differential pathways to adult metabolic dysfunction following poor nutrition at two critical developmental periods in sheep

Differential pathways to adult metabolic dysfunction following poor nutrition at two critical developmental periods in sheep
Differential pathways to adult metabolic dysfunction following poor nutrition at two critical developmental periods in sheep
Epidemiological and experimental studies suggest early nutrition has long-term effects on susceptibility to obesity, cardiovascular and metabolic diseases. Small and large animal models confirm the influence of different windows of sensitivity, from fetal to early postnatal life, on offspring phenotype. We showed previously that undernutrition in sheep either during the first month of gestation or immediately after weaning induces differential, sex-specific changes in adult metabolic and cardiovascular systems. The current study aims to determine metabolic and molecular changes that underlie differences in lipid and glucose metabolism induced by undernutrition during specific developmental periods in male and female sheep. Ewes received 100% (C) or 50% nutritional requirements (U) from 1–31 days gestation, and 100% thereafter. From weaning (12 weeks) to 25 weeks, offspring were then fed either ad libitum (CC, UC) or were undernourished (CU, UU) to reduce body weight to 85% of their individual target. From 25 weeks, all offspring were fed ad libitum. A cohort of late gestation fetuses were studied after receiving either 40% nutritional requirements (1–31 days gestation) or 50% nutritional requirements (104–127 days gestation). Post-weaning undernutrition increased in vivo insulin sensitivity, insulin receptor and glucose transporter 4 expression in muscle, and lowered hepatic methylation at the delta-like homolog 1/maternally expressed gene 3 imprinted cluster in adult females, but not males. Early gestational undernutrition induced lower hepatic expression of gluconeogenic factors in fetuses and reduced in vivo adipose tissue insulin sensitivity in adulthood. In males, undernutrition in early gestation increased adipose tissue lipid handling mechanisms (lipoprotein lipase, glucocorticoid receptor expression) and hepatic methylation within the imprinted control region of insulin-like growth factor 2 receptor in adulthood. Therefore, undernutrition during development induces changes in mechanisms of lipid and glucose metabolism which differ between tissues and sexes dependent on the period of nutritional restriction. Such changes may increase later life obesity and dyslipidaemia risk.
1932-6203
1-13
Poore, Kirsten R.
b9529ba3-6432-4935-b8fd-6e382f11f0ad
Hollis, Lisa J.
3db27dff-d225-46da-97c5-c85cec618735
Murray, Robert J.S.
c3e973b5-525c-49b3-96ee-af60a666a0f4
Warlow, Anna
f49a1986-24bb-4660-9c76-c068e281dd32
Brewin, Andrew
4d0c6703-35f6-450f-84bb-02bd9c0b0ed5
Fulford, Laurence
9b93bc0e-96cd-4d3e-89ac-4677c0c81402
Cleal, Jane K.
18cfd2c1-bd86-4a13-b38f-c321af56da66
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Green, Lucy R.
8a601974-efe5-4916-9268-9e7bc72d89c5
Poore, Kirsten R.
b9529ba3-6432-4935-b8fd-6e382f11f0ad
Hollis, Lisa J.
3db27dff-d225-46da-97c5-c85cec618735
Murray, Robert J.S.
c3e973b5-525c-49b3-96ee-af60a666a0f4
Warlow, Anna
f49a1986-24bb-4660-9c76-c068e281dd32
Brewin, Andrew
4d0c6703-35f6-450f-84bb-02bd9c0b0ed5
Fulford, Laurence
9b93bc0e-96cd-4d3e-89ac-4677c0c81402
Cleal, Jane K.
18cfd2c1-bd86-4a13-b38f-c321af56da66
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Green, Lucy R.
8a601974-efe5-4916-9268-9e7bc72d89c5

Poore, Kirsten R., Hollis, Lisa J., Murray, Robert J.S., Warlow, Anna, Brewin, Andrew, Fulford, Laurence, Cleal, Jane K., Lillycrop, Karen A., Burdge, Graham C., Hanson, Mark A. and Green, Lucy R. (2014) Differential pathways to adult metabolic dysfunction following poor nutrition at two critical developmental periods in sheep. PLoS ONE, 9 (3), 1-13. (doi:10.1371/journal.pone.0090994). (PMID:24603546)

Record type: Article

Abstract

Epidemiological and experimental studies suggest early nutrition has long-term effects on susceptibility to obesity, cardiovascular and metabolic diseases. Small and large animal models confirm the influence of different windows of sensitivity, from fetal to early postnatal life, on offspring phenotype. We showed previously that undernutrition in sheep either during the first month of gestation or immediately after weaning induces differential, sex-specific changes in adult metabolic and cardiovascular systems. The current study aims to determine metabolic and molecular changes that underlie differences in lipid and glucose metabolism induced by undernutrition during specific developmental periods in male and female sheep. Ewes received 100% (C) or 50% nutritional requirements (U) from 1–31 days gestation, and 100% thereafter. From weaning (12 weeks) to 25 weeks, offspring were then fed either ad libitum (CC, UC) or were undernourished (CU, UU) to reduce body weight to 85% of their individual target. From 25 weeks, all offspring were fed ad libitum. A cohort of late gestation fetuses were studied after receiving either 40% nutritional requirements (1–31 days gestation) or 50% nutritional requirements (104–127 days gestation). Post-weaning undernutrition increased in vivo insulin sensitivity, insulin receptor and glucose transporter 4 expression in muscle, and lowered hepatic methylation at the delta-like homolog 1/maternally expressed gene 3 imprinted cluster in adult females, but not males. Early gestational undernutrition induced lower hepatic expression of gluconeogenic factors in fetuses and reduced in vivo adipose tissue insulin sensitivity in adulthood. In males, undernutrition in early gestation increased adipose tissue lipid handling mechanisms (lipoprotein lipase, glucocorticoid receptor expression) and hepatic methylation within the imprinted control region of insulin-like growth factor 2 receptor in adulthood. Therefore, undernutrition during development induces changes in mechanisms of lipid and glucose metabolism which differ between tissues and sexes dependent on the period of nutritional restriction. Such changes may increase later life obesity and dyslipidaemia risk.

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e-pub ahead of print date: 6 March 2014
Published date: 6 March 2014
Organisations: Human Development & Health, Centre for Biological Sciences

Identifiers

Local EPrints ID: 368061
URI: http://eprints.soton.ac.uk/id/eprint/368061
ISSN: 1932-6203
PURE UUID: eebdcf03-6740-4955-b48c-5c29b508afee
ORCID for Kirsten R. Poore: ORCID iD orcid.org/0000-0002-1455-0615
ORCID for Jane K. Cleal: ORCID iD orcid.org/0000-0001-7978-4327
ORCID for Karen A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Graham C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967
ORCID for Mark A. Hanson: ORCID iD orcid.org/0000-0002-6907-613X
ORCID for Lucy R. Green: ORCID iD orcid.org/0000-0001-7423-9696

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Date deposited: 14 Aug 2014 15:09
Last modified: 12 Nov 2019 02:03

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