Journal article
Prenatal Exposure to Dietary Fat Induces Changes in the Transcriptional Factors, TEF and YAP, Which May Stimulate Differentiation of Peptide Neurons in Rat Hypothalamus
PloS one, v 8(10), pp e77668-e77668
11 Oct 2013
PMCID: PMC3795669
PMID: 24147051
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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Details
- Title
- Prenatal Exposure to Dietary Fat Induces Changes in the Transcriptional Factors, TEF and YAP, Which May Stimulate Differentiation of Peptide Neurons in Rat Hypothalamus
- Creators
- Kinning Poon - Rockefeller UniversitySushma Mandava - Rockefeller UniversityKaren Chen - Rockefeller UniversityJessica R. Barson - Rockefeller UniversitySylvie Buschlen - Rockefeller UniversitySarah F. Leibowitz - Rockefeller University
- Publication Details
- PloS one, v 8(10), pp e77668-e77668
- Publisher
- Public Library Science
- Number of pages
- 12
- Grant note
- 5R01DA021518 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA CEN5401363 / NARSAD R01DA021518 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; College of Medicine; Drexel University
- Web of Science ID
- WOS:000325819400132
- Scopus ID
- 2-s2.0-84885416168
- Other Identifier
- 991020099051104721
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