Effect of maternal restricted diet during late gestation on muscle and bone development in sheep offspring

Changes in intrauterine environment, including nutrient availability, have been associated with fetal programming, contributing to different phenotypes which may determine health and susceptibility to disease throughout life. These changes seem to be mediated through alterations in both anabolic and catabolic hormone levels of maternal, placental and/or fetal origin. The present work aimed to evaluate how maternal under-nutrition during late pregnancy affects muscle and bone growth. Pregnant ewes were divided into two groups, one fed ad libitum and the other fed a restricted diet (50% of total energy requirements) during the last 6 weeks of gestation. Three twin carrying ewes from each feeding group were euthanized 6 days pre parturition. The remaining ewes gave birth normally and reared their lambs. At approximately day 30 post partum, 5 lambs from each of the feeding groups were euthanized and samples collected. Nutrient restriction during late gestation did not affect intrauterine axial growth, although weight at birth and the muscle weight were significantly lower than the ad libitum fed lamb fetuses. Bone development is less affected cf muscle development during periods of maternal feed restriction; however, catch-up growth of muscle occurs when lambs (30 days post-parturition) have access to adequate rations. In utero irrespective of maternal nutrient supply dry muscle mass is correlated (r=0.94) to bone development (bone weight, femur length and femur mineral density). In contrast, post partum growth of and skeleton are less tightly coupled and unaffected by the events in utero. A detailed examination of how maternal nutrient supply affects endocrine parameters in utero will be required to assess if it affects susceptibility post-partum to endocrine dysfunction.info:eu-repo/semantics/publishedVersio

Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring

Maternal caloric restriction during late gestation reduces birth weight, but whether long-term adverse metabolic outcomes of intra-uterine growth retardation (IUGR) are dependent on either accelerated postnatal growth or exposure to an obesogenic environment after weaning is not established. We induced IUGR in twin-pregnant sheep using a 40% maternal caloric restriction commencing from 110 days of gestation until term (∼147 days), compared with mothers fed to 100% of requirements. Offspring were reared either as singletons to accelerate postnatal growth or as twins to achieve standard growth. To promote an adverse phenotype in young adulthood, after weaning, offspring were reared under a low-activity obesogenic environment with the exception of a subgroup of IUGR offspring, reared as twins, maintained in a standard activity environment. We assessed glucose tolerance together with leptin and cortisol responses to feeding in young adulthood when the hypothalamus was sampled for assessment of genes regulating appetite control, energy and endocrine sensitivity. Caloric restriction reduced maternal plasma glucose, raised non-esterified fatty acids, and changed the metabolomic profile, but had no effect on insulin, leptin, or cortisol. IUGR offspring whose postnatal growth was enhanced and were obese showed insulin and leptin resistance plus raised cortisol. This was accompanied by increased hypothalamic gene expression for energy and glucocorticoid sensitivity. These long-term adaptations were reduced but not normalized in IUGR offspring whose postnatal growth was not accelerated and remained lean in a standard post-weaning environment. IUGR results in an adverse metabolic phenotype, especially when postnatal growth is enhanced and offspring progress to juvenile-onset obesity

Pre- and early-postnatal nutrition modify gene and protein expressions of muscle energy metabolism markers and phospholipid fatty acid composition in a muscle type specific manner in sheep.

We previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key muscle determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD) and biceps femoris (BF)) and in the cardiac muscle (ventriculus sinister cordis (VSC)) of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM) or 50% (LOW) of their energy and protein requirements during the last trimester of gestation. From day-3 postpartum to 6-months of age (around puberty), twin offspring received a high-carbohydrate-high-fat (HCHF) or a moderate-conventional (CONV) diet, whereafter all males were slaughtered. Females were subsequently raised on a moderate diet and slaughtered at 2-years of age (young adults). The only long-term consequences of fetal undernutrition observed in adult offspring were lower expressions of the insulin responsive glucose transporter 4 (GLUT4) protein and peroxisome proliferator-activated receptor gamma, coactivator 1α (PGC1α) mRNA in BF, but increased PGC1α expression in VSC. Interestingly, the HCHF diet in early postnatal life was associated with somewhat paradoxically increased expressions in LD of a range of genes (but not proteins) related to glucose uptake, insulin signalling and fatty acid oxidation. Except for fatty acid oxidation genes, these changes persisted into adulthood. No persistent expression changes were observed in BF and VSC. The HCHF diet increased phospholipid ratios of n-6/n-3 polyunsaturated fatty acids in all muscles, even in adults fed identical diets for 1½ years. In conclusion, early postnatal, but not late gestation, nutrition had long-term consequences for a number of determinants of insulin action and metabolism in LD. Tissues other than muscle may account for reduced whole body insulin sensitivity in adult LOW sheep