TY - JOUR
T1 - Chronic circadian disruption on a high-fat diet impairs glucose tolerance
AU - Zitting, Kirsi Marja
AU - Vetrivelan, Ramalingam
AU - Yuan, Robin K.
AU - Vujovic, Nina
AU - Wang, Wei
AU - Bandaru, Sathyajit S.
AU - Quan, Stuart F.
AU - Klerman, Elizabeth B.
AU - Scheer, Frank A.J.L.
AU - Buxton, Orfeu M.
AU - Williams, Jonathan S.
AU - Duffy, Jeanne F.
AU - Saper, Clifford B.
AU - Czeisler, Charles A.
N1 - Publisher Copyright:
© 2022
PY - 2022/5
Y1 - 2022/5
N2 - Background: Nearly 14% of Americans experience chronic circadian disruption due to shift work, increasing their risk of obesity, diabetes, and other cardiometabolic disorders. These disorders are also exacerbated by modern eating habits such as frequent snacking and consumption of high-fat foods. Methods: We investigated the effects of recurrent circadian disruption (RCD) on glucose metabolism in C57BL/6 mice and in human participants exposed to non-24-h light-dark (LD) schedules vs. those on standard 24-h LD schedules. These LD schedules were designed to induce circadian misalignment between behaviors including rest/activity and fasting/eating with the output of the near-24-h central circadian pacemaker, while minimizing sleep loss, and were maintained for 12 weeks in mice and 3 weeks in humans. We examined interactions of these circadian-disrupted schedules compared to control 24-h schedules with a lower-fat diet (LFD, 13% in mouse and 25–27% in humans) and high-fat diet (HFD, 45% in mouse and 45–50% in humans). We also used young vs. older mice to determine whether they would respond differently to RCD. Results: When combined with a HFD, we found that RCD caused significant weight gain in mice and increased body fat in humans, and significantly impaired glucose tolerance and insulin sensitivity in both mice and humans, but this did not occur when RCD was combined with a LFD. This effect was similar in both young and older mice. Conclusion: These results in both humans and a model organism indicate that circadian disruption has an adverse effect on metabolism among individuals eating a high-fat Western-style diet, even in the absence of significant sleep loss, and suggest that reducing dietary fat may protect against the metabolic consequences of a lifestyle (such as shift work) that involves chronic circadian disruption.
AB - Background: Nearly 14% of Americans experience chronic circadian disruption due to shift work, increasing their risk of obesity, diabetes, and other cardiometabolic disorders. These disorders are also exacerbated by modern eating habits such as frequent snacking and consumption of high-fat foods. Methods: We investigated the effects of recurrent circadian disruption (RCD) on glucose metabolism in C57BL/6 mice and in human participants exposed to non-24-h light-dark (LD) schedules vs. those on standard 24-h LD schedules. These LD schedules were designed to induce circadian misalignment between behaviors including rest/activity and fasting/eating with the output of the near-24-h central circadian pacemaker, while minimizing sleep loss, and were maintained for 12 weeks in mice and 3 weeks in humans. We examined interactions of these circadian-disrupted schedules compared to control 24-h schedules with a lower-fat diet (LFD, 13% in mouse and 25–27% in humans) and high-fat diet (HFD, 45% in mouse and 45–50% in humans). We also used young vs. older mice to determine whether they would respond differently to RCD. Results: When combined with a HFD, we found that RCD caused significant weight gain in mice and increased body fat in humans, and significantly impaired glucose tolerance and insulin sensitivity in both mice and humans, but this did not occur when RCD was combined with a LFD. This effect was similar in both young and older mice. Conclusion: These results in both humans and a model organism indicate that circadian disruption has an adverse effect on metabolism among individuals eating a high-fat Western-style diet, even in the absence of significant sleep loss, and suggest that reducing dietary fat may protect against the metabolic consequences of a lifestyle (such as shift work) that involves chronic circadian disruption.
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U2 - 10.1016/j.metabol.2022.155158
DO - 10.1016/j.metabol.2022.155158
M3 - Article
C2 - 35150732
AN - SCOPUS:85126555651
SN - 0026-0495
VL - 130
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
M1 - 155158
ER -