Unacylated ghrelin, leptin, and appetite display diurnal rhythmicity in lean adults

Iain Templeman, Harry A Smith, Jean-Philippe Walhin, Benita Middleton, Javier T Gonzalez, Leonidas G Karagounis, Jonathan D Johnston, James A Betts

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Constant routine and forced desynchrony protocols typically remove the effects of behavioral/environmental cues to examine endogenous circadian rhythms, yet this may not reflect rhythms of appetite regulation in the real world. It is therefore important to understand these rhythms within the same subjects under controlled diurnal conditions of light, sleep, and feeding. Ten healthy adults (9 M/1 F, means ±SD: Age, 30 ± 10 yr; body mass index, 24.1 ± 2.7 kgm2) rested supine in the laboratory for 37 h. All data were collected during the final 24 h of this period (i.e., 0800-0800 h). Participants were fed hourly isocaloric liquid meal replacements alongside appetite assessments during waking before a sleep opportunity from 2200 to 0700 h. Hourly blood samples were collected throughout the 24-h period. Dim light melatonin onset occurred at 2318 ± 46 min. A diurnal rhythm in mean plasma unacylated ghrelin concentration was identified (P = 0.04), with the acrophase occurring shortly after waking (0819), falling to a nadir in the evening with a relative amplitude of 9%. Plasma leptin concentration also exhibited a diurnal rhythm (P < 0.01), with the acrophase occurring shortly after lights-out (0032 h) and the lowest concentrations at midday. The amplitude for this rhythm was 25%. Diurnal rhythms were established in all dimensions of appetite except for sweet preference (P = 0.29), with both hunger (2103 h) and prospective food consumption (1955 h) reaching their peak in the evening before falling to their nadir shortly after waking. Under controlled diurnal conditions, simultaneous measurement of leptin, unacylated ghrelin, and subjective appetite over a 24-h period revealed rhythmicity in appetite regulation in lean, healthy humans

Original languageEnglish
Pages (from-to)1534-1543
Number of pages10
JournalJournal of Applied Physiology
Issue number5
Early online date11 Mar 2021
Publication statusPublished - 31 May 2021

Bibliographical note

Funding Information:
I.T., H.A.S., and J.P.W. declare no conflicts of interest. B.M. is a codirector of Stockgrand Ltd. J.T.G. has received research funding and/or has acted as a consultant for Arla Foods Ingredients, Lucozade Ribena Suntory, Kenniscentrum Suiker and Voeding, and PepsiCo. L.G.K. is an employee of Nestlé Health Sciences. J.D.J. has performed consultancy work for Kellogg Marketing and Sales Company (UK) Limited and has collaborated with the Nestlé Institute of Health Sciences. J.A.B. has received research funding from BBSRC, GlaxoSmithKline, Nestlé Institute of Health Sciences, Lucozade Ribena Suntory, Kellogg’s, PepsiCo, and the Rare Disease Foundation.

Funding Information:
The work was partly funded by the Biotechnology and Biological Sciences Research Council Grant BB/I008470/1 (to J.D.J.). Nestlé Institute of Health Sciences provided funding for consumables.


  • Appetite
  • Circadian rhythms
  • Diurnal
  • Ghrelin
  • Leptin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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