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Am J Physiol Endocrinol Metab (October 13, 2009). doi:10.1152/ajpendo.00505.2009
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RESEARCH ARTICLE

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

Wenche Jorgensen,1,* Christiane Gam,1 Jesper Loevind Andersen,2 Peter Schjerling,3 Morten Scheibye-Knudsen,1 Ole Hartvig Mortensen,1 Niels Grunnet,1 Mette Olaf Nielsen,4 and Bjorn Quistorff1

1University of Copenhagen 2Rigshospitalet, section 9312 3Copenhagen Muscle Research Centre 4University of Copenhagen - Department of Basic Animal and Veterinary Sciences - Animal Nutrition

Submitted 18 August 2009 ; revised 30 September 2009 ; accepted in final form 5 October 2009

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 month of life. We examined mitochondrial function in permeabilized muscle fibres from the lambs at 6 months of age (adolescence) and after 24 months of age (adulthood). The post-partum H-diet to the lambs induced a ~30% increase (P<0.05) of mitochondrial VO2-max and a ~50% increase (P<0.05) of the respiratory coupling ratio (RCR), combined with lower levels of UCP3 and PGC-1{alpha} mRNA levels (P<0.05). These effects proved to be reversible by a normal diet from 6 to 24 months of age. However, at 24 months a long term effect, of the maternal gestational diet restriction (fetal programming) became evident as a lower VO2-max (~40%, P<0.05), a lower state-4 respiration (~40%, P<0.05), and lower RCR (~15%, P<0.05). Both PGC-1{alpha} and UCP3 mRNA levels were increased (P<0.05). Two analysed muscles were differently affected, and muscle rich in type I fibres was more susceptible to fetal programming. We conclude that fetal programming, seen as a reduced VO2-max in adulthood, results from gestational under-nutrition. Post natal high-fat diet results in a pronounced RCR and VO2-max increase in adolescence. However, these effects are reversible by diet correction and are not maintained in adulthood.

Metabolic syndrome; high-fat diet; nutrient restriction; maternal diet



* University of Copenhagen wenche{at}sund.ku.dk







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