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Open AccessArticle

Feeding Stimulates Sphingosine-1-Phosphate Mobilization in Mouse Hypothalamus

1
Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697, USA
2
Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy
3
Department of Biological Chemistry, University of California, Irvine, CA 92697, USA
4
Center for the Study of Cannabis, University of California, Irvine, CA 92697, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(16), 4008; https://doi.org/10.3390/ijms20164008
Received: 7 July 2019 / Revised: 12 August 2019 / Accepted: 15 August 2019 / Published: 17 August 2019
(This article belongs to the Collection Sphingolipid Signaling in Health and Disease)
Previous studies have shown that the sphingolipid-derived mediator sphingosine-1-phosphate (S1P) reduces food intake by activating G protein-coupled S1P receptor-1 (S1PR1) in the hypothalamus. Here, we examined whether feeding regulates hypothalamic mobilization of S1P and other sphingolipid-derived messengers. We prepared lipid extracts from the hypothalamus of C57Bl6/J male mice subjected to one of four conditions: free feeding, 12 h fasting, and 1 h or 6 h refeeding. Liquid chromatography/tandem mass spectrometry was used to quantify various sphingolipid species, including sphinganine (SA), sphingosine (SO), and their bioactive derivatives SA-1-phosphate (SA1P) and S1P. In parallel experiments, transcription of S1PR1 (encoded in mice by the S1pr1 gene) and of key genes of sphingolipid metabolism (Sptlc2, Lass1, Sphk1, Sphk2) was measured by RT-PCR. Feeding increased levels of S1P (in pmol-mg−1 of wet tissue) and SA1P. This response was accompanied by parallel changes in SA and dihydroceramide (d18:0/18:0), and was partially (SA1P) or completely (S1P) reversed by fasting. No such effects were observed with other sphingolipid species targeted by our analysis. Feeding also increased transcription of Sptlc2, Lass1, Sphk2, and S1pr1. Feeding stimulates mobilization of endogenous S1PR1 agonists S1P and SA1P in mouse hypothalamus, via a mechanism that involves transcriptional up-regulation of de novo sphingolipid biosynthesis. The results support a role for sphingolipid-mediated signaling in the central control of energy balance. View Full-Text
Keywords: Sphingolipids; hypothalamus; feeding; sphingosine-1-phosphate; sphinganine-1-phosphate Sphingolipids; hypothalamus; feeding; sphingosine-1-phosphate; sphinganine-1-phosphate
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Vozella, V.; Realini, N.; Misto, A.; Piomelli, D. Feeding Stimulates Sphingosine-1-Phosphate Mobilization in Mouse Hypothalamus. Int. J. Mol. Sci. 2019, 20, 4008.

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