Abstract
The hypothesis that dietary factors in early life modify the extent of adaptive responses in adult life was tested in rats. During the gestational and lactational periods, pregnant rats were fed either a high-fat (HF) or low-fat (LF) diet (corn oil, 15% or 2%, wt/wt) until 30 days postpartum. The offspring were maintained on standard chow for an additional 100 days and fed a HF diet for 1, 3, 7, or 21 days. Upon challenge for 3 days, rats born to dams fed the HF diet showed a more rapid hypercholesterolemic response when compared with rats born to dams fed a LF diet (mean ± S.D., 151 ± 14 mg/dL v 122 ± 6 mg/dL; P < .001). Higher levels of cholesterol were associated with elevated levels of apolipoprotein (apo) B (24.0 ± 4 mg/dL v 15.8 ± 3 mg/dL; P < .05) and apo E (31.0 ± 4 mg/dL v 24.7 ± 3 mg/dL; P < .05). Further comparison of the hypercholesterolemic response between the two groups of animals showed increases in cholesterol in all major lipoprotein classes, cholesterol enrichment at the expense of triglyceride (TG) in very-low-density lipoprotein (VLDL), and elevation of apo E-containing high-density lipoprotein (HDL). Examination at longer time periods of HF challenge showed that apo E levels of the HF-exposed animals remained elevated compared with similarly challenged rats born to dams fed the LF diet (35 ± 3.8 mg/dL v 26 ± 2.7 mg/dL; P < .05). In contrast, plasma cholesterol and apo B levels did not differ late in the course of the challenge. Our studies also suggest that the gestational period was more important than the lactational period in altering the cholesterolemic response. We conclude that expression of genes regulating cholesterol metabolism in the adult rat can be modulated by maternal diet.
Published Version
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