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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL118601-01A1
Application #
8630702
Study Section
Clinical and Integrative Diabetes and Obesity Study Section (CIDO)
Program Officer
Laposky, Aaron D
Project Start
2014-06-01
Project End
2018-03-31
Budget Start
2014-06-01
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
$645,685
Indirect Cost
$280,461
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115