Fatty Acid de Novo Synthesis in Adult Intrauterine Growth-Restricted Offspring, and Adult Male Response to a High Fat Diet

Abstract

Intrauterine growth restriction (IUGR) with rapid catch-up growth leads to adult obesity and insulin resistance. We have previously shown that IUGR male rats demonstrated increased de novo fatty acid synthesis in the subcutaneous (SC) fat, but not the visceral fat, during the nursing period prior to the onset of obesity. Young IUGR females do not exhibit the same increase. We further hypothesized that in male IUGR offspring, de novo synthesis is a programmed intrinsic effect that persists to adulthood and does not suppress in response to a high fat diet. We measured fatty acid de novo synthesis in IUGR adult males (6 months) using deuterium-enriched drinking water as a stable isotope tracer, then further studied the response after consumption of an isocaloric high fat diet. Baseline de novo synthesis in adult females was also studied at age 9 months. Males demonstrated increased baseline de novo synthesis in both SC fat and visceral fat. Correspondingly, SC and visceral fat protein expression of lipogenic enzymes acetyl-coA carboxylase-α (ACCα) and fatty acid synthase were upregulated. After the isocaloric high fat diet, de novo synthesis was suppressed such that no differences remained between the two groups, although, IUGR SC fat demonstrated persistently increased lipogenic protein expression. In contrast, de novo synthesis among adult females is not impacted in IUGR. In conclusion, enhancement of male IUGR SC fat de novo synthesis appears to be an early consequence of metabolic programming, whereas enhancement in visceral fat appears to be a later consequence.