Uncovering Circadian Mechanisms of Poor Cardiometabolic Health

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Project Summary/Abstract Weight gain and obesity have reached epidemic proportions in modern society. Obesity is a risk factor for numerous metabolic diseases and accounts for ~$147 billion in health care costs each year in the United States, thus making identification of mechanisms for obesity necessary for targeted interventions. In cross-sectional and controlled in-laboratory studies, eating during the night has been found to be a risk factor for weight gain and poor health, yet it is not known how the circadian timing (i.e., the timing of an event in relation to levels of a circadian marker) of food intake in real-world schedules may contribute to disease. In this epidemiological observational prospective cohort, we will elucidate potential circadian mechanisms for weight gain and cardiometabolic disease by studying a natural experiment that occurs when newly-hired transit bus operators transition from a day schedule to an early morning and/or late evening schedule. This allows a unique prospective examination, unlike previous cross-sectional observations, of how changing the circadian timing of food intake impacts energy balance behaviors (i.e., eating, activity, sleep) and cardiometabolic health in real-world settings. We have recently found that the closer an individual eats to their circadian night is associated with a higher percentage of body fat relative to weight. However, from an epidemiological perspective, it is difficult to disentangle the impact of eating at night on metabolism and weight gain through cross-sectional designs. We will utilize an occupational natural experiment in a prospective manner to identify how a rapid transition to eating during the circadian night (when the hormone melatonin is high) alters energy balance behaviors. Our preliminary data suggests new bus drivers gain ~7 pounds in their first year on the job, when they are forced to work at times (early morning or at night, both when melatonin concentrations are elevated) when their circadian clock is promoting fasting and sleep. For this observational prospective cohort, we will measures new drivers circadian timing (melatonin) and track the timing and content of food consumed for 3, 1-week episodes using a time- stamped mobile phone food diary during a pre-service training (baseline day-eating schedule), the first 30-days of driving (acute shift to eating during the circadian night), and at 90-days of driving. Cardiometablic health will be measured after each meal tracking episode. The specific aims of this proposal are to test the hypotheses that the transition to an early morning or late evening schedule will: 1) increase the percentage of daily calories new transit drivers consume, particularly carbohydrates, during the circadian night relative to baseline; 2) reduce energy expenditure through physical activity; and 3) be associated with poorer cardiometabolic health. To achieve my long-term goal of becoming an independent scientist conducting translational sleep and circadian research, this Mentored Research Scientist Development Award will provide further training in the following areas: 1) working with business organizations and labor unions; 2) field work; 3) implementing study procedures into a workplace setting; and 4) incorporation of epidemiological cardiometabolic variables and into research.