Shift work is associated with an increased risk for the development of diabetes, obesity, and cardiovascular disease, which cannot be fully explained by differences in life style and socioeconomic status. Recently, we demonstrated that circadian misalignment, the misalignment between the central circadian pacemaker and the behavioral sleep/wake cycle (that is typical in shift workers), while keeping caloric intake and physical activity constant, leads to adverse metabolic changes. These findings may help explain the adverse health consequences of shift work. More recently, we also demonstrated in a prospective study that the timing of meals predicts the success of weight loss therapy, independent of caloric intake, activity and sleep duration. The importance of meal timing is consistent with animal experimental work showing that normalizing the circadian timing of the fasting/feeding cycle (without normalizing the sleep/wake cycle) prevents such adverse metabolic effects. Furthermore, misalignment between the central pacemaker and the fasting/feeding cycle leads to desynchrony between the central circadian pacemaker and peripheral circadian oscillators in the rest of the body, especially in metabolic organs such as liver and pancreas, a phenomenon known as internal desynchrony, which may relate to the adverse metabolic consequences of circadian misalignment. However, to date there exists no evidence for or against the development of internal desynchrony in humans, likely because of the demanding and complex circadian protocols required to test that hypothesis. In the current proposal, we will test whether manipulating the timing of food intake prevents the adverse metabolic effects of circadian misalignment (Aim 1), and whether desynchrony between the central circadian pacemaker and the behavioral cycle leads to internal desynchrony in humans (Aim 2). Because of the high proportion of the work force exposed to shift work and the grave consequences, this proposal has great clinical relevance and lays the scientific foundation for later development of a novel therapeutic approach against the increased risk for cardiometabolic disorders in this vulnerable population with chronic exposure.
Shift work is associated with circadian misalignment and an increased risk for the development diabetes, obesity, and cardiovascular disease. This research will determine whether manipulation of the feeding schedule can prevent metabolic alterations that can lead to the abovementioned disorders. This research will provide mechanistic insight and may provide a novel therapeutic approach against the increased risk for diabetes, obesity, and cardiovascular disease among shift workers.
| Li, Peng; Yu, Lei; Lim, Andrew S P et al. (2018) Fractal regulation and incident Alzheimer's disease in elderly individuals. Alzheimers Dement 14:1114-1125 |
| Qian, Jingyi; Morris, Christopher J; Caputo, Rosanna et al. (2018) Ghrelin is impacted by the endogenous circadian system and by circadian misalignment in humans. Int J Obes (Lond) : |
| Wefers, Jakob; van Moorsel, Dirk; Hansen, Jan et al. (2018) Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle. Proc Natl Acad Sci U S A 115:7789-7794 |
| Lo, M-T; Bandin, C; Yang, H-W et al. (2018) CLOCK 3111T/C genetic variant influences the daily rhythm of autonomic nervous function: relevance to body weight control. Int J Obes (Lond) 42:190-197 |
| Collado, María Carmen; Engen, Phillip A; Bandín, Cristina et al. (2018) Timing of food intake impacts daily rhythms of human salivary microbiota: a randomized, crossover study. FASEB J 32:2060-2072 |
| Vetter, Céline; Dashti, Hassan S; Lane, Jacqueline M et al. (2018) Night Shift Work, Genetic Risk, and Type 2 Diabetes in the UK Biobank. Diabetes Care 41:762-769 |
| Lopez-Minguez, Jesus; Dashti, Hassan S; Madrid-Valero, Juan J et al. (2018) Heritability of the timing of food intake. Clin Nutr : |
| Swanson, Christine M; Kohrt, Wendy M; Buxton, Orfeu M et al. (2018) The importance of the circadian system & sleep for bone health. Metabolism 84:28-43 |
| Chellappa, Sarah L; Morris, Christopher J; Scheer, Frank A J L (2018) Daily circadian misalignment impairs human cognitive performance task-dependently. Sci Rep 8:3041 |
| Lopez-Minguez, Jesus; Saxena, Richa; Bandín, Cristina et al. (2018) Late dinner impairs glucose tolerance in MTNR1B risk allele carriers: A randomized, cross-over study. Clin Nutr 37:1133-1140 |
Showing the most recent 10 out of 29 publications
