Tanycyte-Independent Control of Hypothalamic Leptin Signaling
Leptin is secreted by adipocytes to regulate appetite and body weight. Recent studies have reported that tanycytes actively transport circulating leptin across the brain barrier into the hypothalamus, and are required for normal levels of hypothalamic leptin signaling. However, direct evidence for l...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2019.00240/full |
| _version_ | 1831521069563904000 |
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| author | Sooyeon Yoo David Cha Dong Won Kim Thanh V. Hoang Seth Blackshaw Seth Blackshaw Seth Blackshaw Seth Blackshaw Seth Blackshaw |
| author_facet | Sooyeon Yoo David Cha Dong Won Kim Thanh V. Hoang Seth Blackshaw Seth Blackshaw Seth Blackshaw Seth Blackshaw Seth Blackshaw |
| author_sort | Sooyeon Yoo |
| collection | DOAJ |
| description | Leptin is secreted by adipocytes to regulate appetite and body weight. Recent studies have reported that tanycytes actively transport circulating leptin across the brain barrier into the hypothalamus, and are required for normal levels of hypothalamic leptin signaling. However, direct evidence for leptin receptor (LepR) expression is lacking, and the effect of tanycyte-specific deletion of LepR has not been investigated. In this study, we analyze the expression and function of the tanycytic LepR in mice. Using single-molecule fluorescent in situ hybridization (smfISH), RT-qPCR, single-cell RNA sequencing (scRNA-Seq), and selective deletion of the LepR in tanycytes, we are unable to detect expression of LepR in the tanycytes. Tanycyte-specific deletion of LepR likewise did not affect leptin-induced pSTAT3 expression in hypothalamic neurons, regardless of whether leptin was delivered by intraperitoneal or intracerebroventricular injection. Finally, we use activity-regulated scRNA-Seq (act-Seq) to comprehensively profile leptin-induced changes in gene expression in all cell types in mediobasal hypothalamus. Clear evidence for leptin signaling is only seen in endothelial cells and subsets of neurons, although virtually all cell types show leptin-induced changes in gene expression. We thus conclude that LepR expression in tanycytes is either absent or undetectably low, that tanycytes do not directly regulate hypothalamic leptin signaling through a LepR-dependent mechanism, and that leptin regulates gene expression in diverse hypothalamic cell types through both direct and indirect mechanisms. |
| first_indexed | 2024-12-13T17:44:28Z |
| format | Article |
| id | doaj.art-c84957d17b8a47fb83b5d2314b39598c |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-13T17:44:28Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-c84957d17b8a47fb83b5d2314b39598c2022-12-21T23:36:39ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-03-011310.3389/fnins.2019.00240449963Tanycyte-Independent Control of Hypothalamic Leptin SignalingSooyeon Yoo0David Cha1Dong Won Kim2Thanh V. Hoang3Seth Blackshaw4Seth Blackshaw5Seth Blackshaw6Seth Blackshaw7Seth Blackshaw8Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, United StatesSolomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, United StatesSolomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, United StatesSolomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, United StatesSolomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Ophthalmology, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University, Baltimore, MD, United StatesCenter for Human Systems Biology, Johns Hopkins University, Baltimore, MD, United StatesSchool of Medicine, Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, United StatesLeptin is secreted by adipocytes to regulate appetite and body weight. Recent studies have reported that tanycytes actively transport circulating leptin across the brain barrier into the hypothalamus, and are required for normal levels of hypothalamic leptin signaling. However, direct evidence for leptin receptor (LepR) expression is lacking, and the effect of tanycyte-specific deletion of LepR has not been investigated. In this study, we analyze the expression and function of the tanycytic LepR in mice. Using single-molecule fluorescent in situ hybridization (smfISH), RT-qPCR, single-cell RNA sequencing (scRNA-Seq), and selective deletion of the LepR in tanycytes, we are unable to detect expression of LepR in the tanycytes. Tanycyte-specific deletion of LepR likewise did not affect leptin-induced pSTAT3 expression in hypothalamic neurons, regardless of whether leptin was delivered by intraperitoneal or intracerebroventricular injection. Finally, we use activity-regulated scRNA-Seq (act-Seq) to comprehensively profile leptin-induced changes in gene expression in all cell types in mediobasal hypothalamus. Clear evidence for leptin signaling is only seen in endothelial cells and subsets of neurons, although virtually all cell types show leptin-induced changes in gene expression. We thus conclude that LepR expression in tanycytes is either absent or undetectably low, that tanycytes do not directly regulate hypothalamic leptin signaling through a LepR-dependent mechanism, and that leptin regulates gene expression in diverse hypothalamic cell types through both direct and indirect mechanisms.https://www.frontiersin.org/article/10.3389/fnins.2019.00240/fullmetabolism and obesityleptinhypothalamustanycyteradial gliasingle cell RNA sequencing |
| spellingShingle | Sooyeon Yoo David Cha Dong Won Kim Thanh V. Hoang Seth Blackshaw Seth Blackshaw Seth Blackshaw Seth Blackshaw Seth Blackshaw Tanycyte-Independent Control of Hypothalamic Leptin Signaling Frontiers in Neuroscience metabolism and obesity leptin hypothalamus tanycyte radial glia single cell RNA sequencing |
| title | Tanycyte-Independent Control of Hypothalamic Leptin Signaling |
| title_full | Tanycyte-Independent Control of Hypothalamic Leptin Signaling |
| title_fullStr | Tanycyte-Independent Control of Hypothalamic Leptin Signaling |
| title_full_unstemmed | Tanycyte-Independent Control of Hypothalamic Leptin Signaling |
| title_short | Tanycyte-Independent Control of Hypothalamic Leptin Signaling |
| title_sort | tanycyte independent control of hypothalamic leptin signaling |
| topic | metabolism and obesity leptin hypothalamus tanycyte radial glia single cell RNA sequencing |
| url | https://www.frontiersin.org/article/10.3389/fnins.2019.00240/full |
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