Impact of Sleep and Meal Timing on Food Intake Regulation

Sleeping patterns affect aspects of metabolism that may impact obesity risk; our lab is interested in studying whether sleep patterns play a role in the development of obesity. Individuals with late bedtimes and late rise times tend to have greater food intake which includes more fast food and sugar-sweetened beverages, less fruits and vegetables [1], larger portions, and later eating times [2] than those with earlier bedtimes. This sleeping pattern is highly prevalent: ~15 million Americans work on shifts other than regular day hours [3] and others subject themselves to 'social jetlag' (time difference between the middle of the sleep episode [midpoint of sleep] on work days and non-work days, similar to travel across time zones) [4]. The shift in sleep and meal times associated with these lifestyles results in misalignment of sleep and eating behaviors with the circadian clocks. These clocks, located in the brain and organs throughout the body, regulate metabolism and behavior and are affected by sleep and feeding. Disruption of clock genes in individual organs may be in part responsible for metabolic dysregulation [5]. Altering the coordination of sleep and meal timing may affect food reward valuation (brain) and metabolism (peripheral organs) to promote obesity and IR, observed more frequently in shift workers. This is the focus of this randomized, crossover, controlled study of 4 phases:

• Normal sleep (Ns; 0000-0800 h), Normal meals (Nm=meals at 1, 5, 11, and 12.5 h after awakening)=Ns/Nm
• Normal sleep (Ns; 0000-0800 h), Late meals (Lm=meals at 4.5, 8.5, 14.5, and 16 h after awakening)=Ns/Lm
• Late sleep (Ls; 0330-1130 h), Normal meals (Nm=meals at 1, 5, 11, and 12.5 h after awakening)=Ls/Nm
• Late sleep (Ls; 0330-1130 h), Late meals (Lm=meals at 4.5, 8.5, 14.5, and 16 h after awakening)=Ls/Lm Aim 1: To determine whether Ls and/or Lm, in individuals with habitual normal sleep duration and timing, alters one or both sides of energy balance, i.e. food intake and energy expenditure (EE), relative to Ns and Nm.
• Hypothesis 1: (a) Ls and Lm will have independent and interactive effects on food intake and EE. Intake at an ad libitum test meal and during a 24 h period, measured after 3 d of each intervention, will be greater during Ls and Lm, and this will be enhanced when Ls and Lm are combined, compared to Ns and Nm. (b) Resting metabolic rate (RMR) will be lower during the Ls and Lm phases, and this will be further reduced when Ls and Lm are combined compared to the Ns and Nm phases (Ns/Nm<Ls/Nm≤Ns/Lm<Ls/Lm).

Aim 2: To determine whether neuronal responses to food stimuli in brain regions related to reward value explain differences in food intake.

• Hypothesis 2: (a) Increased brain activity in response to visual presentation of food stimuli, using functional magnetic resonance imaging (fMRI), will be seen in Ls and Lm compared to Ns and Nm in the insula and the orbitofrontal cortex. Enhanced neuronal activity in response to foods will be most pronounced in the Ls/Lm phase (Ns/Nm<Ls/Nm≤Ns/Lm<Ls/Lm). (b) Neuronal responses to food stimuli will be related to pre-test neuropeptide Y (NPY), hypocretin-1, and subsequent food intake.

Exploratory Aim 3: To determine whether meal or sleep timing affect glucose homeostasis and appetite-regulating hormones.