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.
|Carrasco-Benso, Maria P; Rivero-Gutierrez, Belen; Lopez-Minguez, Jesus et al. (2016) Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity. FASEB J 30:3117-23|
|Morris, Christopher J; Purvis, Taylor E; Mistretta, Joseph et al. (2016) Effects of the Internal Circadian System and Circadian Misalignment on Glucose Tolerance in Chronic Shift Workers. J Clin Endocrinol Metab 101:1066-74|
|Qian, Jingyi; Scheer, Frank A J L (2016) Circadian System and Glucose Metabolism: Implications for Physiology and Disease. Trends Endocrinol Metab 27:282-93|
|Hu, Kun; Riemersma-van der Lek, Rixt F; Patxot, Melissa et al. (2016) Progression of Dementia Assessed by Temporal Correlations of Physical Activity: Results From a 3.5-Year, Longitudinal Randomized Controlled Trial. Sci Rep 6:27742|
|van Moorsel, Dirk; Hansen, Jan; Havekes, Bas et al. (2016) Demonstration of a day-night rhythm in human skeletal muscle oxidative capacity. Mol Metab 5:635-45|
|Lane, Jacqueline M; Chang, Anne-Marie; Bjonnes, Andrew C et al. (2016) Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology. Diabetes 65:1741-51|
|Johnston, Jonathan D; OrdovÃ¡s, JosÃ© M; Scheer, Frank A et al. (2016) Circadian Rhythms, Metabolism, and Chrononutrition in Rodents and Humans. Adv Nutr 7:399-406|
|Morris, Christopher J; Purvis, Taylor E; Hu, Kun et al. (2016) Circadian misalignment increases cardiovascular disease risk factors in humans. Proc Natl Acad Sci U S A 113:E1402-11|
|Morris, Christopher J; Yang, Jessica N; Garcia, Joanna I et al. (2015) Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans. Proc Natl Acad Sci U S A 112:E2225-34|
|Morris, Christopher J; Garcia, Joanna I; Myers, Samantha et al. (2015) The Human Circadian System Has a Dominating Role in Causing the Morning/Evening Difference in Diet-Induced Thermogenesis. Obesity (Silver Spring) 23:2053-8|
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