The nutritional environment encountered during fetal life is strongly implicated as a determinant of lifelong metabolic capacity and risk of disease. Pregnant rats were fed a control or low protein (LP) diet, targeted to early (LPE), mid (LPM), or late (LPL) pregnancy, or throughout gestation (LPA). The offspring were studied at 1, 9 and 18 months of age. All LP exposed groups had similar plasma triglyceride, cholesterol, glucose and insulin concentrations to controls at 1 and 9 months of age, but by 18 months there was evidence of LP-programmed hypertriglyceridemia and insulin resistance. All LP exposed groups exhibited histological evidence of hepatic steatosis and were found to have 2-3 fold more hepatic triglyceride than control animals. These phenotypic changes were accompanied by age-related changes in mRNA and protein expression of the transcription factors SREBP-1c, ChREBP, PPAR γ and PPARα and their respective downstream target genes, ACC-1, FAS, L-PK and MCAD. At 9 months of age the LP groups exhibited suppression of the SREBP-1c related lipogenic pathway, but between 9 and 18 months underwent a switch to increased lipogenic capacity with a lower expression of PPAR γ and MCAD, consistent with reduced lipid oxidation. The findings indicate that prenatal protein restriction programmes development of a metabolic syndrome-like phenotype that develops only with senescence. The data implicate altered expression of SREBP-1c and ChREBP as key mediators of the programmed phenotype, but the basis of the switch in metabolic status that occurred between 9 and 18 months of age is, as yet, unidentified.