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Programmed Alterations in Hypothalamic Neuronal Orexigenic Responses to Ghrelin Following Gestational Nutrient Restriction

Harbor-UCLA Medical Center

^* To whom correspondence should be addressed. E-mail: mikeross{at}ucla.edu.

	Abstract

Intrauterine growth restricted (IUGR) offspring exhibit increased appetite and a propensity to adult obesity. Although the rate of newborn catch-up growth may determine the programming of adult obesity, there is little understanding of mechanisms by which orexigenic pathways are modified. Ghrelin is an orexigenic peptide that acts in the hypothalamic arcuate (ARC) and ventromedial (VMH) nuclei. To examine potential programming effects of IUGR, ghrelin’s actions on ARC and VMH neurons were studied in brain slices of adult offspring previously subjected to maternal food restriction (FR) during pregnancy (FR/AdLib [ad libitum]) and both pregnancy and lactation (FR/FR). FR/FR offspring demonstrated increased baseline neuronal firing frequency in both ARC and VMH when compared with both FR/AdLib and control offspring. Among FR/AdLib pups that exhibit hyperphagia and obesity, ghrelin excited more and inhibited fewer ARC neurons when compared with either FR/FR or controls. These results provide evidence of programming of orexigenic/anorexigenic mechanisms depending on the nutrient levels during pregnancy and newborn periods.

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