title: Changed mitochondrial function by pre- and/or postpartum diet alterations in sheep.
abstract: In a sheep model, we investigated diet effects on skeletal muscle mitochondria to look for fetal programming. During pregnancy, ewes were fed normally (N) or were 50% food restricted (L) during the last trimester, and lambs born to these ewes received a normal (N) or a high-fat diet (H) for the first 6 mo of life. We examined mitochondrial function in permeabilized muscle fibers from the lambs at 6 mo of age (adolescence) and after 24 mo of age (adulthood). The postpartum H diet for the lambs induced an approximately 30% increase (P < 0.05) of mitochondrial VO(2max) and an approximately 50% increase (P < 0.05) of the respiratory coupling ratio (RCR) combined with lower levels of UCP3 and PGC-1alpha mRNA levels (P < 0.05). These effects proved to be reversible by a normal diet from 6 to 24 mo of age. However, at 24 mo, a long-term effect of the maternal gestational diet restriction (fetal programming) became evident as a lower VO(2max) (approximately 40%, P < 0.05), a lower state 4 respiration (approximately 40%, P < 0.05), and lower RCR ( approximately 15%, P < 0.05). Both PGC-1alpha and UCP3 mRNA levels were increased (P < 0.05). Two analyzed muscles were affected differently, and muscle rich in type I fibers was more susceptible to fetal programming. We conclude that fetal programming, seen as a reduced VO(2max) in adulthood, results from gestational undernutrition. Postnatal high-fat diet results in a pronounced RCR and VO(2max) increase in adolescence. However, these effects are reversible by diet correction and are not maintained in adulthood.
authors.affiliation: Department of Biomedical Sciences, Nuclear Magnetic Resonance Center, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. wenche@sund.ku.dk
authors.forename: Wenche
authors.initials: W
authors.lastname: Jørgensen
authors.forename: Christiane
authors.initials: C
authors.lastname: Gam
authors.forename: Jesper Løvind
authors.initials: JL
authors.lastname: Andersen
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.forename: Morten
authors.initials: M
authors.lastname: Scheibye-Knudsen
authors.forename: Ole Hartvig
authors.initials: OH
authors.lastname: Mortensen
authors.forename: Niels
authors.initials: N
authors.lastname: Grunnet
authors.forename: Mette Olaf
authors.initials: MO
authors.lastname: Nielsen
authors.forename: Bjørn
authors.initials: B
authors.lastname: Quistorff
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001706:Biopsy; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D044342:Malnutrition / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D010101:Oxygen Consumption / Q000502:physiology; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014475:Uncoupling Agents / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D047494:PPAR delta; D012333:RNA, Messenger; D014157:Transcription Factors; D014475:Uncoupling Agents