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Meal-feeding promotes skeletal growth by ghrelin-dependent enhancement of growth hormone rhythmicity

Amanda Hornsby, Richard C. Brown, Thomas W. Tilston, Harry A. Smith, Alfonso Moreno-Cabañas Orcid Logo, Bradley Arms-Williams, Anna L. Hopkins, Katie D. Taylor, Simran K.R. Rogaly, Lois H.M. Wells, Jamie J. Walker, Jeffrey Davies Orcid Logo, Yuxiang Sun, Jeffrey M. Zigman Orcid Logo, James A. Betts, Timothy Wells

Journal of Clinical Investigation, Volume: 135, Issue: 12, Start page: e189202

Swansea University Authors: Amanda Hornsby, Jeffrey Davies Orcid Logo

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DOI (Published version): 10.1172/jci189202

Abstract

The physiological impact of ultradian temporal feeding patterns remains a major unanswered question in nutritional science. We have employed automated and nasogastric feeding to address this question in male rodents and human volunteers. While grazing and meal-feeding reduced food intake in parallel...

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Published in: Journal of Clinical Investigation
ISSN: 0021-9738 1558-8238
Published: American Society for Clinical Investigation 2025
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URI: https://cronfa.swan.ac.uk/Record/cronfa69285
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In contrast, bolus enteral infusion elicited post-prandial ghrelin troughs accompanied by reduced circulating GH, with enhanced ultradian rhythmicity. 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spelling 2025-06-24T15:28:31.6027220 v2 69285 2025-04-14 Meal-feeding promotes skeletal growth by ghrelin-dependent enhancement of growth hormone rhythmicity 52a586048b9cb0543fe0f3e112e345c3 Amanda Hornsby Amanda Hornsby true false 2cb3d1d96a7870a84d2f758e865172e6 0000-0002-4234-0033 Jeffrey Davies Jeffrey Davies true false 2025-04-14 The physiological impact of ultradian temporal feeding patterns remains a major unanswered question in nutritional science. We have employed automated and nasogastric feeding to address this question in male rodents and human volunteers. While grazing and meal-feeding reduced food intake in parallel (compared to ad libitum-fed rodents), body length and tibial epiphysial plate width were maintained in meal-fed rodents via the action of ghrelin and its receptor, GHS-R. Grazing and meal-feeding initially suppressed elevated pre-prandial ghrelin levels in rats, followed by either a sustained elevation in ghrelin in grazing rats or pre-prandial ghrelin surges in meal-fed rats. Episodic growth hormone (GH) secretion was largely unaffected in grazing rats, but meal-feeding tripled GH secretion, with burst height augmented and two additional bursts of GH per day. Continuous nasogastric infusion of enteral feed in humans failed to suppress circulating ghrelin, producing continuously elevated circulating GH with minimal rhythmicity. In contrast, bolus enteral infusion elicited post-prandial ghrelin troughs accompanied by reduced circulating GH, with enhanced ultradian rhythmicity. Taken together, our data imply that the contemporary shift from regular meals to snacking behaviour may be detrimental to optimal skeletal growth outcomes by sustaining circulating GH at levels associated with undernourishment and diminishing GH pulsatility. Journal Article Journal of Clinical Investigation 135 12 e189202 American Society for Clinical Investigation 0021-9738 1558-8238 16 6 2025 2025-06-16 10.1172/jci189202 COLLEGE NANME COLLEGE CODE Swansea University Another institution paid the OA fee The authors gratefully acknowledge the financial support of the Bill & Melinda Gates Foundation (Grant: OPP1061040), the Rosetrees Trust (Grant: A2248), the Waterloo Foundation (Grants: 1403/3689, 1403/3758, 1403/4120) and Cardiff University’s School of Biosciences Equipment Fund, Research Contingency Fund and Neuroscience and Mental Health Research Institute Seedcorn Fund and Future Minds Programme. Enteral formula for the human feeding study was supplied by Nestlé Health Sciences. J.J.W acknowledges financial support from the Medical Research Council (Grants MR/N008936/1 and MR/T032480/1). 2025-06-24T15:28:31.6027220 2025-04-14T10:08:19.8622250 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Amanda Hornsby 1 Richard C. Brown 2 Thomas W. Tilston 3 Harry A. Smith 4 Alfonso Moreno-Cabañas 0000-0002-5117-425x 5 Bradley Arms-Williams 6 Anna L. Hopkins 7 Katie D. Taylor 8 Simran K.R. Rogaly 9 Lois H.M. Wells 10 Jamie J. Walker 11 Jeffrey Davies 0000-0002-4234-0033 12 Yuxiang Sun 13 Jeffrey M. Zigman 0000-0003-3477-1295 14 James A. Betts 15 Timothy Wells 16 69285__34566__40c9ad0b9c164d1dad19452fe6f32ef5.pdf 69285.VOR.pdf 2025-06-24T15:25:52.6357586 Output 12633462 application/pdf Version of Record true © 2025, Hornsby et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. true eng http://creativecommons.org/licenses/by/4.0/
title Meal-feeding promotes skeletal growth by ghrelin-dependent enhancement of growth hormone rhythmicity
spellingShingle Meal-feeding promotes skeletal growth by ghrelin-dependent enhancement of growth hormone rhythmicity
Amanda Hornsby
Jeffrey Davies
title_short Meal-feeding promotes skeletal growth by ghrelin-dependent enhancement of growth hormone rhythmicity
title_full Meal-feeding promotes skeletal growth by ghrelin-dependent enhancement of growth hormone rhythmicity
title_fullStr Meal-feeding promotes skeletal growth by ghrelin-dependent enhancement of growth hormone rhythmicity
title_full_unstemmed Meal-feeding promotes skeletal growth by ghrelin-dependent enhancement of growth hormone rhythmicity
title_sort Meal-feeding promotes skeletal growth by ghrelin-dependent enhancement of growth hormone rhythmicity
author_id_str_mv 52a586048b9cb0543fe0f3e112e345c3
2cb3d1d96a7870a84d2f758e865172e6
author_id_fullname_str_mv 52a586048b9cb0543fe0f3e112e345c3_***_Amanda Hornsby
2cb3d1d96a7870a84d2f758e865172e6_***_Jeffrey Davies
author Amanda Hornsby
Jeffrey Davies
author2 Amanda Hornsby
Richard C. Brown
Thomas W. Tilston
Harry A. Smith
Alfonso Moreno-Cabañas
Bradley Arms-Williams
Anna L. Hopkins
Katie D. Taylor
Simran K.R. Rogaly
Lois H.M. Wells
Jamie J. Walker
Jeffrey Davies
Yuxiang Sun
Jeffrey M. Zigman
James A. Betts
Timothy Wells
format Journal article
container_title Journal of Clinical Investigation
container_volume 135
container_issue 12
container_start_page e189202
publishDate 2025
institution Swansea University
issn 0021-9738
1558-8238
doi_str_mv 10.1172/jci189202
publisher American Society for Clinical Investigation
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 1
active_str 0
description The physiological impact of ultradian temporal feeding patterns remains a major unanswered question in nutritional science. We have employed automated and nasogastric feeding to address this question in male rodents and human volunteers. While grazing and meal-feeding reduced food intake in parallel (compared to ad libitum-fed rodents), body length and tibial epiphysial plate width were maintained in meal-fed rodents via the action of ghrelin and its receptor, GHS-R. Grazing and meal-feeding initially suppressed elevated pre-prandial ghrelin levels in rats, followed by either a sustained elevation in ghrelin in grazing rats or pre-prandial ghrelin surges in meal-fed rats. Episodic growth hormone (GH) secretion was largely unaffected in grazing rats, but meal-feeding tripled GH secretion, with burst height augmented and two additional bursts of GH per day. Continuous nasogastric infusion of enteral feed in humans failed to suppress circulating ghrelin, producing continuously elevated circulating GH with minimal rhythmicity. In contrast, bolus enteral infusion elicited post-prandial ghrelin troughs accompanied by reduced circulating GH, with enhanced ultradian rhythmicity. Taken together, our data imply that the contemporary shift from regular meals to snacking behaviour may be detrimental to optimal skeletal growth outcomes by sustaining circulating GH at levels associated with undernourishment and diminishing GH pulsatility.
published_date 2025-06-16T05:27:46Z
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