Prevention of Programmed Hyperleptinemia and Hypertension by Postnatal Dietary ω-3 Fatty Acids

Abstract

Fetal programming is now recognized as a key determinant of the adult phenotype, with major implications for adult-onset diseases including hypertension. Two mediators of fetal programming are maternal nutrition and fetal glucocorticoid exposure. Recent studies show that postnatal dietary manipulations can exacerbate programming effects, but whether programming effects can be attenuated by postnatal dietary manipulations, and thus provide a possible therapeutic strategy, is unknown. In this study, we tested the hypothesis that a postnatal diet enriched with long-chain omega-3 fatty acids attenuates programmed hyperleptinemia and hypertension. Pregnant rats were treated with dexamethasone (Dex) from d 13 to term, and offspring were cross-fostered to mothers on either a standard diet or a diet high in omega-3 fatty acids and remained on these diets postweaning. Maternal Dex reduced birthweight and delayed the onset of puberty in offspring. Hyperleptinemia (associated with elevated leptin mRNA expression in adipose tissue) and hypertension were evident in offspring by 6 months of age in Dex-exposed animals consuming a standard diet, but these effects were completely blocked by a high omega-3 diet. These results demonstrate for the first time that manipulation of postnatal diet can limit adverse outcomes of fetal programming, with programmed hyperleptinemia and hypertension prevented by a postnatal diet enriched with omega-3 fatty acids. This raises the possibility that dietary supplementation with omega-3 fatty acids may provide a viable therapeutic option for preventing and/or reducing adverse programming outcomes in humans.

Size and phospholipid coating of lipid droplets in the diet of young mice modify body fat accumulation in adulthood

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Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective

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Developmental programming of the metabolic syndrome - critical windows for intervention

“…The role of possible direct nutritional interventions was highlighted in the work by Wyrwoll et al [161] . Pregnant rats were treated with DEX from d13 to term, and offspring were cross-fostered to mothers on either a standard diet or a diet high in omega-3 fatty acids and remained on these diets post-weaning.…”