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 ∼30% increase ( P < 0.05) of mitochondrial V̇o2maxand an ∼50% increase ( P < 0.05) of the respiratory coupling ratio (RCR) combined with lower levels of UCP3 and PGC-1α 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 V̇o2max(∼40%, P < 0.05), a lower state 4 respiration (∼40%, P < 0.05), and lower RCR (∼15%, P < 0.05). Both PGC-1α 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 V̇o2maxin adulthood, results from gestational undernutrition. Postnatal high-fat diet results in a pronounced RCR and V̇o2maxincrease in adolescence. However, these effects are reversible by diet correction and are not maintained in adulthood.