Early-Life Lipid Exposure Induces Lasting Skeletal Muscle Remodeling Via Fetal Programming in Male Wistar Rats

BACKGROUND: Omega-3 (n-3) fatty acid consumption is recommended during pregnancy due to its beneficial effects on fetal development, particularly brain formation. Although there are various recommendations regarding its use, ideal intake levels are not well established. Western diets, rich in vegetable oils, increase lipid bioavailability, and the effects of excessive exposure to fatty acids during development are not yet fully understood. This study evaluated the long-term effects of maternal supplementation with n-3 and n-6 fatty acids on offspring skeletal muscle. METHODS: Wistar rats were divided into three groups: control (CT), fish oil (FO; n-3), and soybean oil (SO; n-6). Supplementation (4 g/kg) began before mating and continued through gestation and lactation. After weaning, male offspring were maintained on standard chow without further supplementation and were euthanized at 60 d of age. RESULTS: Compared with the CT group, the FO and SO groups showed reduced body size, increased adiposity, and elevated plasma cholesterol and triglycerides. In the plantar muscle, both supplemented groups exhibited decreased length and cross-sectional area, as well as a lower proportion of type I and IIA fibers. Histological analysis revealed increased capillary density, number of myonuclei, and neuromuscular junction area. Molecular markers indicated reduced GLUT4 expression and increased MMP9 levels, with the FO group showing more pronounced changes. CONCLUSION: The present study demonstrates that excessive maternal fatty acid exposure during critical developmental windows induces persistent skeletal muscle remodeling in male offspring. Early exposure was associated with shifts in fiber type composition, altered fiber size, increased collagen deposition, structural changes to the neuromuscular junctions, and a reduced myonuclear domain, despite maintenance on a standard diet post-weaning.