Short and long-term influences of intra-uterine growth restriction on muscle and adipose tissue properties and metabolic flexibility

Intrauterine growth restriction (IUGR) is associated withseveral health problems throughout life. Our program aimedat investigating the mechanisms underlying adipose tissue andskeletal muscle development in IUGR pigs, a species ofimportance for meat industry worldwide and a broadlyused biomedical model for adiposity. Pairs of piglets werechosen within litters to have either a medium or a smallweight at different stages of gestation or at birth. Because ofthe hypothesis of a relationship between high-protein (HP)intake in IUGR children and their later adiposity, a subset ofIUGR piglets was fed HP formula during suckling, whereasothers received a control formula (AP) that mimicked the sowmilk composition. In skeletal muscle, the ratio between adultfast and embryonic myosin heavy-chain isoforms was twofoldlower in small fetuses than in their medium littermates at2 days before birth, denoting a lower muscular maturity inIUGR animals. In subcutaneous fat, IUGR counteracted thenormal fall of DLK1/Pref-1 expression during gestation, andblunted the temporal increase in expression levels of manydifferentiating and lipogenic genes; the differences betweenweight groups were exacerbated around birth. These differenceswere not associated with modifications in circulating concentrationsof energy-producing metabolites between weight groups.[br/]The distribution of HP formula to IUGR piglets resulted inaccelerated growth rate and in a temporary reduction inadiposity (until weaning) compared with piglets fed APformula. This was associated with a decrease in the expressionlevels of genes related to glucose utilization and lipidanabolism in adipose tissues. In 160-day-old pigs havingbeing fed HP formula, adipocytes were enlarged and theirlipogenic rates were reduced. Thus, IUGR affects the temporaldevelopment of muscle and adipose tissue. Altogether, dietarystrategies at different periods should be further tested tomodulate stem cell lineage, tissue development and reinstatingoptimal growth trajectories.