Pre- and postnatal nutrition in sheep affects ß-cell secretion and hypothalamic control

Anna Hauntoft Kongsted; Sanne Vinter Husted; Malin P. Thygesen; Vibeke Grøsfjeld Christensen; Dominique Blache; Anders Tolver; Torben Larsen; Bjørn Quistorff; Mette Olaf Nielsen

doi:10.1530/JOE-13-0099

Pre- and postnatal nutrition in sheep affects ß-cell secretion and hypothalamic control

Anna Hauntoft Kongsted, Sanne Vinter Husted, Malin P. Thygesen, Vibeke Grøsfjeld Christensen, Dominique Blache, Anders Tolver, Torben Larsen, Bjørn Quistorff, Mette Olaf Nielsen

10 Citationer (Scopus)

Abstract

Maternal undernutrition increases the risk of type 2 diabetes and metabolic syndrome later in life, particularly upon postnatal exposure to a high-energy diet. However, dysfunctions of, for example, the glucose-insulin axis are not readily detectable by conventional tests early in life, making it difficult to identify individuals at risk. Thus, other methods are required.We hypothesised that prenatally undernourished individuals (but not postnatally overnourished ones) are adapted to a life withlimited food availability, which would be evident under conditions reflecting starvation, stress and short-term abundance of food. In this study, twinpregnant sheep were fed diets meeting 100% (NORM) or50%(LOW) of energy and protein requirements during the last trimester. Twin offspring were fed eithera normal moderate (CONV) diet or a high-carbohydrate-high-fat (HCHF) diet from 3 days to 6 months of age (approximately puberty) and the same moderate diet thereafter until 2 years of age (young adulthood;only females), resultingin four groups:NORM-CONV, LOW-CONV,NORM-HCHF and LOW-HCHF. At the age of 6months and 2 years respectively, they were subjected to fasting and propionate (nutrient abundance)andadrenalinchallenges.At6monthsofage,postnatalHCHF diet exposure caused metabolic alterations, reflecting hypertriglyceridaemia and altered pancreatic β-cell secretion. Irrespective of postnatal diet, prenatal undernutritionwas found to be associated with unexpected endocrine responses of leptin, IGF1 and cortisol during fasting (lackofor theopposite response comparedwiththe controls) in2-year-oldadults. Inconclusion, a HCHF diet interfered with bβ-cell function, whereas maternal undernutrition did notlead to any changes in the LOWoffspring, except to abnormal hormone responses, suggesting that fetal programming interferes with hypothalamic integration of important endocrine axis.

Originalsprog	Engelsk
Tidsskrift	Journal of Endocrinology
Vol/bind	219
Sider (fra-til)	159-171
Antal sider	13
ISSN	0022-0795
DOI	https://doi.org/10.1530/JOE-13-0099
Status	Udgivet - 2013

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title = "Pre- and postnatal nutrition in sheep affects {\ss}-cell secretion and hypothalamic control",

abstract = "Maternal undernutrition increases the risk of type 2 diabetes and metabolic syndrome later in life, particularly upon postnatal exposure to a high-energy diet. However, dysfunctions of, for example, the glucose-insulin axis are not readily detectable by conventional tests early in life, making it difficult to identify individuals at risk. Thus, other methods are required.We hypothesised that prenatally undernourished individuals (but not postnatally overnourished ones) are adapted to a life withlimited food availability, which would be evident under conditions reflecting starvation, stress and short-term abundance of food. In this study, twinpregnant sheep were fed diets meeting 100% (NORM) or50%(LOW) of energy and protein requirements during the last trimester. Twin offspring were fed eithera normal moderate (CONV) diet or a high-carbohydrate-high-fat (HCHF) diet from 3 days to 6 months of age (approximately puberty) and the same moderate diet thereafter until 2 years of age (young adulthood;only females), resultingin four groups:NORM-CONV, LOW-CONV,NORM-HCHF and LOW-HCHF. At the age of 6months and 2 years respectively, they were subjected to fasting and propionate (nutrient abundance)andadrenalinchallenges.At6monthsofage,postnatalHCHF diet exposure caused metabolic alterations, reflecting hypertriglyceridaemia and altered pancreatic β-cell secretion. Irrespective of postnatal diet, prenatal undernutritionwas found to be associated with unexpected endocrine responses of leptin, IGF1 and cortisol during fasting (lackofor theopposite response comparedwiththe controls) in2-year-oldadults. Inconclusion, a HCHF diet interfered with bβ-cell function, whereas maternal undernutrition did notlead to any changes in the LOWoffspring, except to abnormal hormone responses, suggesting that fetal programming interferes with hypothalamic integration of important endocrine axis.",

author = "Kongsted, {Anna Hauntoft} and Husted, {Sanne Vinter} and Thygesen, {Malin P.} and Christensen, {Vibeke Gr{\o}sfjeld} and Dominique Blache and Anders Tolver and Torben Larsen and Bj{\o}rn Quistorff and Nielsen, {Mette Olaf}",

year = "2013",

doi = "10.1530/JOE-13-0099",

language = "English",

volume = "219",

pages = "159--171",

journal = "Journal of Endocrinology",

issn = "0022-0795",

publisher = "BioScientifica Ltd.",

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TY - JOUR

T1 - Pre- and postnatal nutrition in sheep affects ß-cell secretion and hypothalamic control

AU - Kongsted, Anna Hauntoft

AU - Husted, Sanne Vinter

AU - Thygesen, Malin P.

AU - Christensen, Vibeke Grøsfjeld

AU - Blache, Dominique

AU - Tolver, Anders

AU - Larsen, Torben

AU - Quistorff, Bjørn

AU - Nielsen, Mette Olaf

PY - 2013

Y1 - 2013

N2 - Maternal undernutrition increases the risk of type 2 diabetes and metabolic syndrome later in life, particularly upon postnatal exposure to a high-energy diet. However, dysfunctions of, for example, the glucose-insulin axis are not readily detectable by conventional tests early in life, making it difficult to identify individuals at risk. Thus, other methods are required.We hypothesised that prenatally undernourished individuals (but not postnatally overnourished ones) are adapted to a life withlimited food availability, which would be evident under conditions reflecting starvation, stress and short-term abundance of food. In this study, twinpregnant sheep were fed diets meeting 100% (NORM) or50%(LOW) of energy and protein requirements during the last trimester. Twin offspring were fed eithera normal moderate (CONV) diet or a high-carbohydrate-high-fat (HCHF) diet from 3 days to 6 months of age (approximately puberty) and the same moderate diet thereafter until 2 years of age (young adulthood;only females), resultingin four groups:NORM-CONV, LOW-CONV,NORM-HCHF and LOW-HCHF. At the age of 6months and 2 years respectively, they were subjected to fasting and propionate (nutrient abundance)andadrenalinchallenges.At6monthsofage,postnatalHCHF diet exposure caused metabolic alterations, reflecting hypertriglyceridaemia and altered pancreatic β-cell secretion. Irrespective of postnatal diet, prenatal undernutritionwas found to be associated with unexpected endocrine responses of leptin, IGF1 and cortisol during fasting (lackofor theopposite response comparedwiththe controls) in2-year-oldadults. Inconclusion, a HCHF diet interfered with bβ-cell function, whereas maternal undernutrition did notlead to any changes in the LOWoffspring, except to abnormal hormone responses, suggesting that fetal programming interferes with hypothalamic integration of important endocrine axis.

AB - Maternal undernutrition increases the risk of type 2 diabetes and metabolic syndrome later in life, particularly upon postnatal exposure to a high-energy diet. However, dysfunctions of, for example, the glucose-insulin axis are not readily detectable by conventional tests early in life, making it difficult to identify individuals at risk. Thus, other methods are required.We hypothesised that prenatally undernourished individuals (but not postnatally overnourished ones) are adapted to a life withlimited food availability, which would be evident under conditions reflecting starvation, stress and short-term abundance of food. In this study, twinpregnant sheep were fed diets meeting 100% (NORM) or50%(LOW) of energy and protein requirements during the last trimester. Twin offspring were fed eithera normal moderate (CONV) diet or a high-carbohydrate-high-fat (HCHF) diet from 3 days to 6 months of age (approximately puberty) and the same moderate diet thereafter until 2 years of age (young adulthood;only females), resultingin four groups:NORM-CONV, LOW-CONV,NORM-HCHF and LOW-HCHF. At the age of 6months and 2 years respectively, they were subjected to fasting and propionate (nutrient abundance)andadrenalinchallenges.At6monthsofage,postnatalHCHF diet exposure caused metabolic alterations, reflecting hypertriglyceridaemia and altered pancreatic β-cell secretion. Irrespective of postnatal diet, prenatal undernutritionwas found to be associated with unexpected endocrine responses of leptin, IGF1 and cortisol during fasting (lackofor theopposite response comparedwiththe controls) in2-year-oldadults. Inconclusion, a HCHF diet interfered with bβ-cell function, whereas maternal undernutrition did notlead to any changes in the LOWoffspring, except to abnormal hormone responses, suggesting that fetal programming interferes with hypothalamic integration of important endocrine axis.

U2 - 10.1530/JOE-13-0099

DO - 10.1530/JOE-13-0099

M3 - Journal article

C2 - 24096964

SN - 0022-0795

VL - 219

SP - 159

EP - 171

JO - Journal of Endocrinology

JF - Journal of Endocrinology

ER -

Pre- and postnatal nutrition in sheep affects ß-cell secretion and hypothalamic control

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