Leptin increases sympathetic nerve activity via induction of its own receptor in the paraventricular nucleus
Whether leptin acts in the paraventricular nucleus (PVN) to increase sympathetic nerve activity (SNA) is unclear, since PVN leptin receptors (LepR) are sparse. We show in rats that PVN leptin slowly increases SNA to muscle and brown adipose tissue, because it induces the expression of its own recept...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/55357 |
| _version_ | 1818028439471390720 |
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| author | Zhigang Shi Nicole E Pelletier Jennifer Wong Baoxin Li Andrei D Sdrulla Christopher J Madden Daniel L Marks Virginia L Brooks |
| author_facet | Zhigang Shi Nicole E Pelletier Jennifer Wong Baoxin Li Andrei D Sdrulla Christopher J Madden Daniel L Marks Virginia L Brooks |
| author_sort | Zhigang Shi |
| collection | DOAJ |
| description | Whether leptin acts in the paraventricular nucleus (PVN) to increase sympathetic nerve activity (SNA) is unclear, since PVN leptin receptors (LepR) are sparse. We show in rats that PVN leptin slowly increases SNA to muscle and brown adipose tissue, because it induces the expression of its own receptor and synergizes with local glutamatergic neurons. PVN LepR are not expressed in astroglia and rarely in microglia; instead, glutamatergic neurons express LepR, some of which project to a key presympathetic hub, the rostral ventrolateral medulla (RVLM). In PVN slices from mice expressing GCaMP6, leptin excites glutamatergic neurons. LepR are expressed mainly in thyrotropin-releasing hormone (TRH) neurons, some of which project to the RVLM. Injections of TRH into the RVLM and dorsomedial hypothalamus increase SNA, highlighting these nuclei as likely targets. We suggest that this neuropathway becomes important in obesity, in which elevated leptin maintains the hypothalamic pituitary thyroid axis, despite leptin resistance. |
| first_indexed | 2024-12-10T05:03:49Z |
| format | Article |
| id | doaj.art-33a2b5efc6bb4037b6a70e91f1714d8d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T05:03:49Z |
| publishDate | 2020-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-33a2b5efc6bb4037b6a70e91f1714d8d2022-12-22T02:01:18ZengeLife Sciences Publications LtdeLife2050-084X2020-06-01910.7554/eLife.55357Leptin increases sympathetic nerve activity via induction of its own receptor in the paraventricular nucleusZhigang Shi0https://orcid.org/0000-0002-5828-1904Nicole E Pelletier1Jennifer Wong2Baoxin Li3Andrei D Sdrulla4Christopher J Madden5Daniel L Marks6https://orcid.org/0000-0003-2675-7047Virginia L Brooks7https://orcid.org/0000-0001-6709-6631Department of Physiology and Pharmacology, Portland, United StatesDepartment of Physiology and Pharmacology, Portland, United StatesDepartment of Physiology and Pharmacology, Portland, United StatesDepartment of Physiology and Pharmacology, Portland, United StatesDepartment of Anesthesiology and Perioperative Medicine, Portland, United StatesDepartment of Neurological Surgery, Portland, United StatesDepartment of Pediatrics, Pape Family Pediatric Research Institute, Brenden-Colson Center for Pancreatic Care Oregon Health & Science University, Portland, United StatesDepartment of Physiology and Pharmacology, Portland, United StatesWhether leptin acts in the paraventricular nucleus (PVN) to increase sympathetic nerve activity (SNA) is unclear, since PVN leptin receptors (LepR) are sparse. We show in rats that PVN leptin slowly increases SNA to muscle and brown adipose tissue, because it induces the expression of its own receptor and synergizes with local glutamatergic neurons. PVN LepR are not expressed in astroglia and rarely in microglia; instead, glutamatergic neurons express LepR, some of which project to a key presympathetic hub, the rostral ventrolateral medulla (RVLM). In PVN slices from mice expressing GCaMP6, leptin excites glutamatergic neurons. LepR are expressed mainly in thyrotropin-releasing hormone (TRH) neurons, some of which project to the RVLM. Injections of TRH into the RVLM and dorsomedial hypothalamus increase SNA, highlighting these nuclei as likely targets. We suggest that this neuropathway becomes important in obesity, in which elevated leptin maintains the hypothalamic pituitary thyroid axis, despite leptin resistance.https://elifesciences.org/articles/55357sympathetic nerve activityparaventricular nucleusbrown adipose tissueglutamatergic neuronsthyrotropin releasing hormoneleptin |
| spellingShingle | Zhigang Shi Nicole E Pelletier Jennifer Wong Baoxin Li Andrei D Sdrulla Christopher J Madden Daniel L Marks Virginia L Brooks Leptin increases sympathetic nerve activity via induction of its own receptor in the paraventricular nucleus eLife sympathetic nerve activity paraventricular nucleus brown adipose tissue glutamatergic neurons thyrotropin releasing hormone leptin |
| title | Leptin increases sympathetic nerve activity via induction of its own receptor in the paraventricular nucleus |
| title_full | Leptin increases sympathetic nerve activity via induction of its own receptor in the paraventricular nucleus |
| title_fullStr | Leptin increases sympathetic nerve activity via induction of its own receptor in the paraventricular nucleus |
| title_full_unstemmed | Leptin increases sympathetic nerve activity via induction of its own receptor in the paraventricular nucleus |
| title_short | Leptin increases sympathetic nerve activity via induction of its own receptor in the paraventricular nucleus |
| title_sort | leptin increases sympathetic nerve activity via induction of its own receptor in the paraventricular nucleus |
| topic | sympathetic nerve activity paraventricular nucleus brown adipose tissue glutamatergic neurons thyrotropin releasing hormone leptin |
| url | https://elifesciences.org/articles/55357 |
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