Changed mitochondrial function by pre- and/or postpartum diet alterations in sheep

Am J Physiol Endocrinol Metab. 2009 Dec;297(6):E1349-57. doi: 10.1152/ajpendo.00505.2009. Epub 2009 Oct 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biopsy
  • DNA, Mitochondrial / chemistry
  • DNA, Mitochondrial / genetics
  • Female
  • Fetal Development / physiology*
  • Malnutrition / metabolism
  • Maternal Nutritional Physiological Phenomena / physiology*
  • Mitochondria, Muscle / metabolism
  • Mitochondria, Muscle / physiology*
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / physiology
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiology*
  • Oxygen Consumption / physiology
  • PPAR delta / genetics
  • PPAR delta / metabolism
  • Pregnancy
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sheep / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / physiology
  • Uncoupling Agents / metabolism


  • DNA, Mitochondrial
  • PPAR delta
  • RNA, Messenger
  • Transcription Factors
  • Uncoupling Agents