The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake
Peptide YY (PYY3-36) is a post-prandially released gut hormone with potent appetite-reducing activity, the mechanism of action of which is not fully understood. Unravelling how this system physiologically regulates food intake may help unlock its therapeutic potential, whilst minimising unwanted eff...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-03-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877824000267 |
| _version_ | 1797272497666654208 |
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| author | Aldara Martin Alonso Simon C. Cork Phyllis Phuah Benjamin Hansen Mariana Norton Sijing Cheng Xiang Xu Kinga Suba Yue Ma Georgina KC. Dowsett John A. Tadross Brian YH. Lam Giles SH. Yeo Herbert Herzog Stephen R. Bloom Myrtha Arnold Walter Distaso Kevin G. Murphy Victoria Salem |
| author_facet | Aldara Martin Alonso Simon C. Cork Phyllis Phuah Benjamin Hansen Mariana Norton Sijing Cheng Xiang Xu Kinga Suba Yue Ma Georgina KC. Dowsett John A. Tadross Brian YH. Lam Giles SH. Yeo Herbert Herzog Stephen R. Bloom Myrtha Arnold Walter Distaso Kevin G. Murphy Victoria Salem |
| author_sort | Aldara Martin Alonso |
| collection | DOAJ |
| description | Peptide YY (PYY3-36) is a post-prandially released gut hormone with potent appetite-reducing activity, the mechanism of action of which is not fully understood. Unravelling how this system physiologically regulates food intake may help unlock its therapeutic potential, whilst minimising unwanted effects. Here we demonstrate that germline and post-natal targeted knockdown of the PYY3-36 preferring receptor (neuropeptide Y (NPY) Y2 receptor (Y2R)) in the afferent vagus nerve is required for the appetite inhibitory effects of physiologically-released PYY3-36, but not peripherally administered pharmacological doses. Post-natal knockdown of the Y2R results in a transient body weight phenotype that is not evident in the germline model. Loss of vagal Y2R signalling also results in altered meal patterning associated with accelerated gastric emptying. These results are important for the design of PYY-based anti-obesity agents. |
| first_indexed | 2024-03-07T14:29:12Z |
| format | Article |
| id | doaj.art-8ca434c5412d4079a5b6bb6f4eff13e9 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-03-07T14:29:12Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-8ca434c5412d4079a5b6bb6f4eff13e92024-03-06T05:26:42ZengElsevierMolecular Metabolism2212-87782024-03-0181101895The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intakeAldara Martin Alonso0Simon C. Cork1Phyllis Phuah2Benjamin Hansen3Mariana Norton4Sijing Cheng5Xiang Xu6Kinga Suba7Yue Ma8Georgina KC. Dowsett9John A. Tadross10Brian YH. Lam11Giles SH. Yeo12Herbert Herzog13Stephen R. Bloom14Myrtha Arnold15Walter Distaso16Kevin G. Murphy17Victoria Salem18Section of Investigative Medicine and Endocrinology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United KingdomSection of Investigative Medicine and Endocrinology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom; School of Medicine, Faculty of Health, Education, Medicine & Social Care, Anglia Ruskin University, Chelmsford, CM1 1SQ, United KingdomSection of Investigative Medicine and Endocrinology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United KingdomDepartment of Bioengineering, Imperial College London, London, United KingdomSection of Investigative Medicine and Endocrinology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United KingdomSection of Investigative Medicine and Endocrinology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United KingdomDepartment of Bioengineering, Imperial College London, London, United KingdomDepartment of Bioengineering, Imperial College London, London, United KingdomSection of Investigative Medicine and Endocrinology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United KingdomMedical Research Council Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, United KingdomMedical Research Council Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, United KingdomMedical Research Council Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, United KingdomMedical Research Council Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, United KingdomNeuroscience Division, Garvan Institute of Medical Research, Darlinghurst, AustraliaSection of Investigative Medicine and Endocrinology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United KingdomDepartment of Health Sciences and Technology, ETH Zurich, Schwerzenbach, SwitzerlandImperial College Business School, Imperial College London, United KingdomSection of Investigative Medicine and Endocrinology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United KingdomSection of Investigative Medicine and Endocrinology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom; Department of Bioengineering, Imperial College London, London, United Kingdom; Corresponding author. Section of Investigative Medicine and Endocrinology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom.Peptide YY (PYY3-36) is a post-prandially released gut hormone with potent appetite-reducing activity, the mechanism of action of which is not fully understood. Unravelling how this system physiologically regulates food intake may help unlock its therapeutic potential, whilst minimising unwanted effects. Here we demonstrate that germline and post-natal targeted knockdown of the PYY3-36 preferring receptor (neuropeptide Y (NPY) Y2 receptor (Y2R)) in the afferent vagus nerve is required for the appetite inhibitory effects of physiologically-released PYY3-36, but not peripherally administered pharmacological doses. Post-natal knockdown of the Y2R results in a transient body weight phenotype that is not evident in the germline model. Loss of vagal Y2R signalling also results in altered meal patterning associated with accelerated gastric emptying. These results are important for the design of PYY-based anti-obesity agents.http://www.sciencedirect.com/science/article/pii/S2212877824000267Vagus nervePYYAppetiteGut hormones |
| spellingShingle | Aldara Martin Alonso Simon C. Cork Phyllis Phuah Benjamin Hansen Mariana Norton Sijing Cheng Xiang Xu Kinga Suba Yue Ma Georgina KC. Dowsett John A. Tadross Brian YH. Lam Giles SH. Yeo Herbert Herzog Stephen R. Bloom Myrtha Arnold Walter Distaso Kevin G. Murphy Victoria Salem The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake Molecular Metabolism Vagus nerve PYY Appetite Gut hormones |
| title | The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake |
| title_full | The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake |
| title_fullStr | The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake |
| title_full_unstemmed | The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake |
| title_short | The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake |
| title_sort | vagus nerve mediates the physiological but not pharmacological effects of pyy3 36 on food intake |
| topic | Vagus nerve PYY Appetite Gut hormones |
| url | http://www.sciencedirect.com/science/article/pii/S2212877824000267 |
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