The human circadian system regulates hunger independently of behavioral factors, resulting in a trough in the biological morning and a peak in the biological evening. However, the role of the only known orexigenic hormone, ghrelin, in this circadian rhythm is unknown. Furthermore, although shift work is an obesity risk factor, the separate effects of the endogenous circadian system, the behavioral cycle, and circadian misalignment on ghrelin has not been systematically studied. Here we show—by using two 8-day laboratory protocols—that circulating active (acylated) ghrelin levels are significantly impacted by endogenous circadian phase in healthy adults. Active ghrelin levels were higher in the biological evening than the biological morning (fasting +15.1%, P = 0.0001; postprandial +10.4%, P = 0.0002), consistent with the circadian variation in hunger (P = 0.028). Moreover, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial active ghrelin levels (+5.4%; P = 0.04). While not significantly influencing hunger (P > 0.08), circadian misalignment increased appetite for energy-dense foods (all P < 0.05). Our results provide possible mechanisms for the endogenous circadian rhythm in hunger, as well as for the increased risk of obesity among shift workers.
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We thank the research volunteers and Brigham and Women’s Hospital’s Center for Clinical Investigation nursing and technical staff. This study was supported by NIH Grant R01HL094806 (FAJLS) and UL1RR025758 (to Harvard University and Brigham and Women’s Hospital). J.Q. was supported in part by American Diabetes Association grant #1-17-PDF-103 (JQ). RC was supported in part by the Minerva Scholarship and the Trustee Fund. MG was supported in part by The Spanish Government of Investigation, Development and Innovation (SAF2017-84135-R) including FEDER co-funding, and NIDDK R01DK105072. FAJLS was supported in part by NIH grants R01HL094806, R01HL118601, R01DK099512, R01DK102696, and R01DK105072 (FAJLS).
Conflict of interest
CJM reports receiving salary from Grünenthal Ltd, UK., which relationship is not related to the present article. FAJLS received speaker fees from Bayer Healthcare, Sentara Healthcare, Philips, Kellogg Company, Vanda Pharmaceuticals, and Pfizer. The remaining authors declare that they have no conflict of interest.
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Qian, J., Morris, C.J., Caputo, R. et al. Ghrelin is impacted by the endogenous circadian system and by circadian misalignment in humans. Int J Obes 43, 1644–1649 (2019). https://doi.org/10.1038/s41366-018-0208-9
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