Fatty acid metabolic programming in intrauterine growth restriction: Underlying mechanisms and postnatal consequences

Intrauterine growth restriction (IUGR) is a major cause of perinatal morbidity and significantly increases the risk of metabolic syndrome in adulthood. Instead of being a simple adaptive response to intrauterine stress, reprogramming of lipid metabolism acts as a core toxic effect pathway, mediating the link between adverse prenatal exposure and lifelong metabolic dysfunction. This review focuses on fetal fatty acid (FA) metabolic perturbations in IUGR, emphasising the dysregulation of key processes: FA transport, de novo synthesis, and desaturation/elongation. We examine the underlying molecular mechanisms of these toxic effects caused by disruption, including epigenetic regulation, oxidative stress-induced mitochondrial toxicity, and dysregulated signalling pathways. Furthermore, we evaluate targeted interventions to reverse toxic effects related to FA metabolism in IUGR. These include amino acid supplementation, supplementation with specific fatty acids, targeted probiotics, and trace element supplementation. These strategies show promise in reprogramming toxic metabolic phenotypes and reducing adverse postnatal outcomes. In conclusion, this review emphasises the pivotal role of FA metabolism in mediating developmental toxicity induced by prenatal exposure in compromised foetuses. It provides a mechanistic framework for understanding the toxic origins of metabolic diseases and offers actionable insights for preventing or reversing IUGR-related developmental toxicity.