Leptin suppresses development of GLP-1 inputs to the paraventricular nucleus of the hypothalamus.
| Autor: | Biddinger JE; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, United States., Lazarenko RM; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, United States., Scott MM; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, United States., Simerly R; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, United States. |
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| Jazyk: | angličtina |
| Zdroj: | ELife [Elife] 2020 Nov 18; Vol. 9. Date of Electronic Publication: 2020 Nov 18. |
| DOI: | 10.7554/eLife.59857 |
| Abstrakt: | The nucleus of the solitary tract (NTS) is critical for the central integration of signals from visceral organs and contains preproglucagon (PPG) neurons, which express leptin receptors in the mouse and send direct projections to the paraventricular nucleus of the hypothalamus (PVH). Here, we visualized projections of PPG neurons in leptin-deficient Lep ob/ob mice and found that projections from PPG neurons are elevated compared with controls, and PPG projections were normalized by targeted rescue of leptin receptors in LepRb TB/TB mice, which lack functional neuronal leptin receptors. Moreover, Lep ob/ob and LepRb TB/TB mice displayed increased levels of neuronal activation in the PVH following vagal stimulation, and whole-cell patch recordings of GLP-1 receptor-expressing PVH neurons revealed enhanced excitatory neurotransmission, suggesting that leptin acts cell autonomously to suppress representation of excitatory afferents from PPG neurons, thereby diminishing the impact of visceral sensory information on GLP-1 receptor-expressing neurons in the PVH. Competing Interests: JB, RL, MS, RS No competing interests declared (© 2020, Biddinger et al.) |
| Databáze: | MEDLINE |
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