Long-Term Impacts of Foetal Malnutrition Followed by Early Postnatal Obesity on Fat Distribution Pattern and Metabolic Adaptability in Adult Sheep.
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 2½ 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 intra-abdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, urea-nitrogen, 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.
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Prabhat
P
Khanal
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Lærke
L
Johnsen
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Anne Marie Dixen
AM
Axel
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Pernille Willert
PW
Hansen
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Anna Hauntoft
AH
Kongsted
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Nette Brinch
NB
Lyckegaard
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Mette Olaf
MO
Nielsen
D050154:Adiposity; D000821:Animal Feed; D053180:Animal Nutrition Sciences; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D005260:Female; D048070:Fetal Nutrition Disorders / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D050152:Intra-Abdominal Fat; D008297:Male; D009751:Nutritional Requirements; D009765:Obesity / Q000209:etiology*; D009929:Organ Size; D044343:Overnutrition / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D012737:Sex Factors; D012756:Sheep; D034561:Sheep, Domestic / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin