title: Pre-natal undernutrition and post-natal overnutrition are associated with permanent changes in hepatic metabolism markers and fatty acid composition in sheep.
abstract: OBJECTIVE
  Determine the impacts of pre- and early-post-natal nutrition on selected markers of hepatic glucose and fat metabolism.
  
  
  METHODS
  Twin-bearing ewes were fed 100% (NORM) or 50% (LOW) of protein and energy requirements during the last 6-weeks of gestation. Twin-lambs received either a high-carbohydrate high-fat (HCHF) or conventional (CONV) diet from 3 days to 6 months of age (around puberty), whereafter lambs from the four subgroups were slaughtered (16 males/3 females). Remaining lambs (19 females) were fed a moderate diet and slaughtered at 2 years of age (young adults).
  
  
  RESULTS
  Pre-natal LOW nutrition was associated with increased hepatic triglyceride, ceramide and free fatty acid content in adulthood (not observed in lambs), which was accompanied by up-regulated early-stage insulin signalling as reflected by increased INSRβ and PI3K-p110 protein expression. The HCHF diet increased hepatic triglyceride content in lambs, associated with down-regulated expressions of energy-metabolism-related genes (GLUT1, PPARα, SREBP1c, PEPCK). These post-natal effects were not observed in adult HCHF sheep, after they had received a moderate (body-fat correcting) diet for 1.5 years. Interestingly, pre-natal LOW nutrition induced permanent alterations in hepatic phospholipids' fatty acid composition. Thus, the amount of linoleic acid (C18 : 2 ∆(9,12)) was significantly increased and composition of rumen-derived fatty acids were altered, indicating changed composition of rumenal microbiota.
  
  
  CONCLUSIONS
  Hepatic insulin signalling and linoleic and microbial-derived fatty acid content in phospholipids are targets of foetal programming induced by late-gestation undernutrition. Future studies are required to explain their cause-effect associations with increased risks of developing hepatic steatosis and insulin insensitivity in adulthood.
authors: Faculty of Health and Medical Sciences, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark; Centre for Fetal Programming, Copenhagen, Denmark.
authors: L
authors: L
authors: Hou
authors: L I
authors: LI
authors: Hellgren
authors: A H
authors: AH
authors: Kongsted
authors: A
authors: A
authors: Vaag
authors: M O
authors: MO
authors: Nielsen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004032:Diet; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology*; D005227:Fatty Acids / Q000737:chemistry*; D005260:Female; D050356:Lipid Metabolism / Q000502:physiology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D044342:Malnutrition / Q000150:complications; D044343:Overnutrition / Q000150:complications*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000473:pathology; D039401:Prenatal Nutritional Physiological Phenomena; D060888:Real-Time Polymerase Chain Reaction; D012756:Sheep
chemical_list: D005227:Fatty Acids
keywords: childhood obesity; dietary intervention; foetal programming; hepatic insulin resistance; polyunsaturated fatty acids