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

Jorgensen W, Gam C, Andersen JL, Schjerling P, ScheibyeKnudsen M, Mortensen OH, Grunnet N, Nielsen MO, Quistorff B. Changed mitochondrial function by pre- and/or postpartum diet alterations in sheep. Am J Physiol Endocrinol Metab 297: E1349-E1357, 2009. First published October 13, 2009; doi:10.1152/ajpendo.00505.2009.-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 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 similar to 30% increase (P < 0.05) of mitochondrial (V) over dot O-2max and an similar to 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 mo of age. However, at 24 mo, a long-term effect of the maternal gestational diet restriction (fetal programming) became evident as a lower (V) over dot O-2max (similar to 40%, P < 0.05), a lower state 4 respiration (similar to 40%, P < 0.05), and lower RCR (similar to 15%, P < 0.05). Both PGC-1 alpha 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 (V) over dot O-2max in adulthood, results from gestational undernutrition. Postnatal high-fat diet results in a pronounced RCR and (V) over dot O-2max increase in adolescence. However, these effects are reversible by diet correction and are not maintained in adulthood.