Implications of Circadian Variation of Human Endocannabinoid Levels on Obesity Risk

The purpose of this study is to examine how the timing of eating changes 24hr profiles of lipids involved in eating for pleasure and how the body makes and uses energy (metabolism).

The timing of food intake and caloric distribution across the 24hr day are emerging as contributing factors to weight gain. The idea that not only what you eat, but when you eat can contribute to weight gain has garnered interest from both the scientific community and the public. In fact, the distribution of caloric intake over the 24hr day has been recently recognized as a potential source of "circadian misalignment" which can result in adverse health outcomes, including overeating, impaired glucose tolerance and insulin sensitivity. Moreover, reward driven eating (eating for the pleasurable aspect instead of energy need) generally results in caloric intake well in excess of energy requirements and is recognized as a major culprit in the epidemic of obesity. The endocannabinoid (eCB) system is involved in both homeostatic processes (energy need only) that govern food intake, and has been shown to play a key role in reward eating. Thus, the role of circadian organization of the eCB system and how misalignment may contribute to overeating, overweight, obesity, and diabetes is the main focus of this study. The overall goal is to determine whether the timing of food intake is a major determinant of the 24 hour variation in eCB activity that in turn affects hunger and appetite, glucose metabolism, and insulin sensitivity. This study will focus on overweight individuals who are at high risk of obesity but are still on a trajectory that can potentially be reversed by lifestyle changes. Following a careful assessment of the subject's habitual sleep and meal timing and caloric distribution under real life conditions, a short laboratory study will determine whether participants who consume more of their daily calories later in the day (later dietary chronotype) display delays in the eCB rhythm and lower insulin sensitivity. During a 6-day in patient intervention, combining laboratory and ambulatory procedures, study procedures will assess the effect of experimentally changing caloric distribution across the day, advancing versus delaying the dietary chronotype. The outcome measures will be the timing of the daily peak of the eCB rhythm and insulin sensitivity. Identification of circadian misalignment of the eCB system as a mediator of increased food intake and reduced insulin sensitivity may help develop novel preventive strategies.

Eligibility Criteria:
Inclusion Criteria:

* self-report sleeping between 7-hrs/night and 9-hrs/night, between 22:00 and 08:00
* no previously diagnosed sleep disorders (including obstructive sleep apnea (OSA))
* no existing diagnosis of prediabetes or diabetes
* no history of endocrine dysfunction
* no history of psychiatric, cardiovascular, or eating disorders
* must not have a gastro-intestinal disease that requires dietary adjustment
* currently taking no medications (including birth control)

Exclusion Criteria:

* drug and nicotine use, habitual alcohol use of more than 2 drinks per day, and caffeine intake of more than 300 mg per day
* anyone who has participated in medically managed weight loss program within the past year
* anyone who has undergone bariatric surgery
* must not have dietary restrictions
* must not work night shifts or crossed any time zones in the month prior to the study.