The cellular factors involved in this stimulatory effect on the differentiation and expression of peptide neurons are unknown but are likely to involve transcriptional regulators of neuronal differentiation, many of which, with the exception of c-Fos and CREB, have never been studied in relation to the orexigenic peptides in the hypothalamus. Further, prenatal HFD exposure increases the peptide-expressing neuroprogenitor cell population in embryos, which later differentiate into functional peptide neurons. Maternal ingestion of a HFD stimulates neurogenesis in early embryonic hypothalamus and increases the number of neurons that express neuropeptides known to stimulate ingestive behavior. The hypothalamus, which is an important part of the brain that controls energy homeostasis by regulating food intake and energy expenditure, has been shown to be markedly affected by prenatal exposure to a HFD. Clinical and animal studies have attributed this rise, in part, to fetal programming produced by maternal obesity and overconsumption of a fat-rich diet, which in the offspring increases preference for a high-fat diet (HFD) and risk for higher weight gain and metabolic disorders. Obesity is a growing epidemic, with the latest National Health and Nutrition Survey finding that 36% of adults and 17% of adolescents and children are obese. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. ![]() This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was supported by the NIH Grant 5R01DA021518, and by NARSAD grant CEN5401363. Received: FebruAccepted: SeptemPublished: October 11, 2013Ĭopyright: © 2013 Poon et al. ![]() PLoS ONE 8(10):Įditor: Thierry Alquier, CRCHUM-Montreal Diabetes Research Center, Canada These findings suggest that prenatal HFD exposure inactivates both hypothalamic TEF and YAP, by either decreasing their levels or increasing their inactive form, and that this contributes to the stimulatory effect of HFD on ENK expression and possibly the differentiation of ENK-expressing neurons.Ĭitation: Poon K, Mandava S, Chen K, Barson JR, Buschlen S, Leibowitz SF (2013) Prenatal Exposure to Dietary Fat Induces Changes in the Transcriptional Factors,TEF and YAP, Which May Stimulate Differentiation of Peptide Neurons in Rat Hypothalamus. Genetic knockdown of TEF or YAP stimulated ENK expression in hypothalamic neurons, supporting a close relationship between these transcription factors and neuropeptide. Increased YAP inactivity by HFD was further evidenced by a decrease in number and fluorescence intensity of YAP-containing neurons, although the density of YAP/ENK co-labeled neurons was unaltered. A close relationship between TEF and ENK was suggested by the finding that TEF co-localizes with this peptide in hypothalamic neurons and HFD reduced the density of TEF/ENK co-labeled neurons, even while the number and fluorescence intensity of single-labeled TEF neurons were increased. This was accompanied by increased density and fluorescence intensity of ENK neurons. Similarly, HFD-exposed embryos at embryonic day 19 (E19) showed in whole hypothalamus significantly decreased levels of YAP mRNA and protein and TEF mRNA, and increased levels of inactive TEF protein, suggesting that HFD inactivates TEF and YAP. ![]() The HFD offspring at postnatal day 15 (P15) exhibited in the hypothalamic paraventricular nucleus a significant reduction in YAP mRNA and protein, and increased levels of inactive and total TEF protein, with no change in mRNA. In rat embryos and postnatal offspring prenatally exposed to a HFD compared to chow, changes in hypothalamic TEF and YAP and their relationship to the orexigenic peptide, enkephalin (ENK), were measured. ![]() To examine possible mechanisms that mediate this phenomenon, this study investigated the transcriptional factor, transcription enhancer factor-1 (TEF), and co-activator, Yes-associated protein (YAP), which when inactivated stimulate neuronal differentiation. Gestational exposure to a high-fat diet (HFD) stimulates the differentiation of orexigenic peptide-expressing neurons in the hypothalamus of offspring.
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