Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA.
Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Neurology, Program in Neuroscience and Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Metabolism. 2022 May;130:155158. doi: 10.1016/j.metabol.2022.155158. Epub 2022 Feb 9.
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.
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.
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.
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.
由于轮班工作，近 14%的美国人经历慢性昼夜节律紊乱，增加了他们肥胖、糖尿病和其他心血管代谢紊乱的风险。这些疾病也因现代饮食习惯而恶化，如频繁吃零食和摄入高脂肪食物。
我们研究了反复的昼夜节律紊乱（RCD）对 C57BL/6 小鼠和暴露于非 24 小时明暗（LD）时间表的人类参与者的葡萄糖代谢的影响，与那些遵循标准 24 小时 LD 时间表的参与者相比。这些 LD 时间表旨在诱导行为（包括休息/活动和禁食/进食）与接近 24 小时中央生物钟起搏器的输出之间的昼夜节律失配，同时最大限度地减少睡眠损失，并在小鼠中维持 12 周，在人类中维持 3 周。我们研究了这些昼夜节律紊乱的时间表与控制 24 小时时间表（低脂肪饮食（LFD，小鼠中为 13%，人类中为 25-27%）和高脂肪饮食（HFD，小鼠中为 45%，人类中为 45-50%））的相互作用。我们还使用年轻和年老的小鼠来确定它们是否会对 RCD 有不同的反应。
当与 HFD 结合时，我们发现 RCD 导致小鼠体重显著增加和体脂增加，以及小鼠和人类的葡萄糖耐量和胰岛素敏感性显著受损，但当与 LFD 结合时则不会。这种影响在年轻和年老的小鼠中是相似的。
这些在人类和模型生物中的结果表明，即使在没有明显睡眠损失的情况下，昼夜节律紊乱对摄入高脂肪西式饮食的个体的代谢也有不利影响，并表明减少饮食中的脂肪可能有助于预防涉及慢性昼夜节律紊乱的生活方式（如轮班工作）的代谢后果。
