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

School of Anatomy and Human Biology (C.S.W., P.J.M., B.J.W.), The University of Western Australia, Nedlands, Perth, Western Australia 6009, Australia; and School of Medicine and Pharmacology, Royal Perth Hospital Unit (T.A.M., I.B.P.), The University of Western Australia, Perth, Western Australia 6001, Australia

Address all correspondence and requests for reprints to: Brendan J. Waddell, School of Anatomy and Human Biology, The University of Western Australia, Nedlands, Perth, Western Australia 6009, Australia. E-mail: bwaddell{at}anhb.uwa.edu.au.

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 -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 -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 -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 -3 fatty acids. This raises the possibility that dietary supplementation with -3 fatty acids may provide a viable therapeutic option for preventing and/or reducing adverse programming outcomes in humans.

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