Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 47, Pages 23806-23812Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1914003116
Keywords
sex difference; circadian disruption; shift work; appetite; energy metabolism
Categories
Funding
- National Institutes of Health (NIH) [R01HL094806]
- National Center for Research Resources [UL1RR025758]
- American Diabetes Association [1-17-PDF-103]
- NIH [R01DK102696, R01DK099512, R01HL118601, R01DK105072, R01HL140574]
- Minerva Scholarship
- Trustee Fund
- Spanish Government of Investigation, Development and Innovation - FEDER [SAF2017-84135-R]
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Shift work causes circadian misalignment and is a risk factor for obesity. While some characteristics of the human circadian system and energy metabolism differ between males and females, little is known about whether sex modulates circadian misalignment effects on energy homeostasis. Here we show-using a randomized crossover design with two 8-d laboratory protocols in 14 young healthy adults (6 females)-that circadian misalignment has sex-specific influences on energy homeostasis independent of behavioral/environmental factors. First, circadian misalignment affected 24-h average levels of the satiety hormone leptin sex-dependently (P < 0.0001), with a similar to 7% decrease in females (P < 0.05) and an similar to 11% increase in males (P < 0.0001). Consistently, circadian misalignment also increased the hunger hormone ghrelin by similar to 8% during wake periods in females (P < 0.05) without significant effect in males. Females reported reduced fullness, consistent with their appetite hormone changes. However, males reported a rise in cravings for energy-dense and savory foods not consistent with their homeostatic hormonal changes, suggesting involvement of hedonic appetite pathways in males. Moreover, there were significant sex-dependent effects of circadian misalignment on respiratory quotient (P < 0.01), with significantly reduced values (P < 0.01) in females when misaligned, and again no significant effects in males, without sex-dependent effects on energy expenditure. Changes in sleep, thermoregulation, behavioral activity, lipids, and catecholamine levels were also assessed. These findings demonstrate that sex modulates the effects of circadian misalignment on energy metabolism, indicating possible sex-specific mechanisms and countermeasures for obesity in male and female shift workers.
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