Journal article
Regulation of the orexigenic neuropeptide, enkephalin, by PPARδ and fatty acids in neurons of the hypothalamus and forebrain
Journal of neurochemistry, v 135(5), pp 918-931
Dec 2015
PMID: 26332891
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Ingestion of a high-fat diet composed mainly of the saturated fatty acid, palmitic (PA), and the unsaturated fatty acid, oleic (OA), stimulates transcription in the brain of the opioid neuropeptide, enkephalin (ENK), which promotes intake of substances of abuse. To understand possible underlying mechanisms, this study examined the nuclear receptors, peroxisome proliferator-activated receptors (PPARs), and tested in hypothalamic and forebrain neurons from rat embryos whether PPARs regulate endogenous ENK and the fatty acids themselves affect these PPARs and ENK. The first set of experiments demonstrated that knocking down PPARδ, but not PPARα or PPARγ, increased ENK transcription, activation of PPARδ by an agonist decreased ENK levels, and PPARδ neurons coexpressed ENK, suggesting that PPARδ negatively regulates ENK. In the second set of experiments, PA treatment of hypothalamic and forebrain neurons had no effect on PPARδ protein while stimulating ENK mRNA and protein, whereas OA increased both mRNA and protein levels of PPARδ in forebrain neurons while having no effect on ENK mRNA and increasing ENK levels. These findings show that PA has a strong, stimulatory effect on ENK and weak effect on PPARδ protein, whereas OA has a strong stimulatory effect on PPARδ and weak effect on ENK, consistent with the inhibitory effect of PPARδ on ENK. They suggest a function for PPARδ, perhaps protective in nature, in embryonic neurons exposed to fatty acids from a fat-rich diet and provide evidence for a mechanism contributing to differential effects of saturated and monounsaturated fatty acids on neurochemical systems involved in consummatory behavior. Our findings show that PPARδ in forebrain and hypothalamic neurons negatively regulates enkephalin (ENK), a peptide known to promote ingestive behavior. This inverse relationship is consistent with our additional findings, that a saturated (palmitic; PA) compared to a monounsaturated fatty acid (oleic; OA) has a strong stimulatory effect on ENK and weak effect on PPARδ. These results suggest that PPARδ protects against the neuronal effects of fatty acids, which differentially affect neurochemical systems involved in ingestive behavior.
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Details
- Title
- Regulation of the orexigenic neuropeptide, enkephalin, by PPARδ and fatty acids in neurons of the hypothalamus and forebrain
- Creators
- Kinning Poon - Rockefeller UniversityMohammad Alam - Rockefeller UniversityOlga Karatayev - Rockefeller UniversityJessica R Barson - Rockefeller UniversitySarah F Leibowitz - Rockefeller University
- Publication Details
- Journal of neurochemistry, v 135(5), pp 918-931
- Publisher
- Wiley
- Grant note
- UL1 TR000043 / NCATS NIH HHS R21 AA020593 / NIAAA NIH HHS K99 AA021782 / NIAAA NIH HHS K99AA021782 / NIAAA NIH HHS F32DK100058 / NIDDK NIH HHS 1R21 AA020593 / NIAAA NIH HHS F32 DK100058 / NIDDK NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; College of Medicine; Drexel University
- Web of Science ID
- WOS:000367191500008
- Scopus ID
- 2-s2.0-84955319231
- Other Identifier
- 991020100202404721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences