Long-term impacts of foetal malnutrition followed by early postnatal obesity on fat distribution pattern and metabolic adaptability in adult sheep

TY - JOUR

T1 - Long-term impacts of foetal malnutrition followed by early postnatal obesity on fat distribution pattern and metabolic adaptability in adult sheep

AU - Khanal, Prabhat

AU - Johnsen, Lærke

AU - Axel, Anne Marie Dixen

AU - Hansen, Pernille Willert

AU - Kongsted, Anna Hauntoft

AU - Lyckegaard, Nette Brinch

AU - Nielsen, Mette Olaf

PY - 2016/6/1

Y1 - 2016/6/1

N2 - We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin-pregnant ewes were fed NORM (100% of daily energy and protein requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein requirements) diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF) or moderate (CONV) diets until 6 months of age, and a moderate (obesity correcting) diet thereafter. At 21/2 years of age (adulthood), plasma metabolite profiles during fasting, glucose, insulin and propionate (in fed and fasted states) tolerance tests were examined. Organ weights were determined at autopsy. Early obesity development was associated with lack of expansion of perirenal, but not other adipose tissues from adolescence to adulthood, resulting in 10% unit increased proportion of mesenteric of intraabdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, ureanitrogen, creatinine, and lactate. Sex specific differences were observed, particularly with respect to fat deposition, but direction of responses to early nutrition impacts were similar. However, prenatal undernutrition induced greater metabolic alterations in adult females than males. Foetal undernutrition, but not overnutrition, predisposed for adult hypercholesterolaemia, hyperureaemia, hypercreatinaemia and hyperlactataemia, which became manifested only in combination with early obesity development. Perirenal expandability may play a special role in this context. Differential nutrition recommendations may be advisable for individuals with low versus high birth weights.

AB - We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin-pregnant ewes were fed NORM (100% of daily energy and protein requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein requirements) diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF) or moderate (CONV) diets until 6 months of age, and a moderate (obesity correcting) diet thereafter. At 21/2 years of age (adulthood), plasma metabolite profiles during fasting, glucose, insulin and propionate (in fed and fasted states) tolerance tests were examined. Organ weights were determined at autopsy. Early obesity development was associated with lack of expansion of perirenal, but not other adipose tissues from adolescence to adulthood, resulting in 10% unit increased proportion of mesenteric of intraabdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, ureanitrogen, creatinine, and lactate. Sex specific differences were observed, particularly with respect to fat deposition, but direction of responses to early nutrition impacts were similar. However, prenatal undernutrition induced greater metabolic alterations in adult females than males. Foetal undernutrition, but not overnutrition, predisposed for adult hypercholesterolaemia, hyperureaemia, hypercreatinaemia and hyperlactataemia, which became manifested only in combination with early obesity development. Perirenal expandability may play a special role in this context. Differential nutrition recommendations may be advisable for individuals with low versus high birth weights.

U2 - 10.1371/journal.pone.0156700

DO - 10.1371/journal.pone.0156700

M3 - Journal article

C2 - 27257993

SN - 1932-6203

VL - 11

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 6

M1 - e0156700

ER -