Logo image
Back
Prenatal Exposure to Dietary Fat Induces Changes in the Transcriptional Factors, TEF and YAP, Which May Stimulate Differentiation of Peptide Neurons in Rat Hypothalamus
Journal article   Open access   Peer reviewed

Prenatal Exposure to Dietary Fat Induces Changes in the Transcriptional Factors, TEF and YAP, Which May Stimulate Differentiation of Peptide Neurons in Rat Hypothalamus

Kinning Poon, Sushma Mandava, Karen Chen, Jessica R. Barson, Sylvie Buschlen and Sarah F. Leibowitz
PloS one, v 8(10), pp e77668-e77668
11 Oct 2013
DOI: https://doi.org/10.1371/journal.pone.0077668
PMID: 24147051
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0077668&type=printableView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1371/journal.pone.0077668View
Published, Version of Record (VoR) Open

Abstract

Multidisciplinary Sciences Science & Technology Science & Technology - Other Topics
Gestational exposure to a high-fat diet (HFD) stimulates the differentiation of orexigenic peptide-expressing neurons in the hypothalamus of offspring. 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. 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. 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. 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. This was accompanied by increased density and fluorescence intensity of ENK neurons. 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. 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. Genetic knockdown of TEF or YAP stimulated ENK expression in hypothalamic neurons, supporting a close relationship between these transcription factors and neuropeptide. 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.

Metrics

8 Record Views
14 citations in Web of Science
15 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Cell Biology
Logo image