Effects of Sleep Restriction on BAT Activation in Humans
Condition: Sleep Deprivation; Obesity
MeSH terms: Sleep Deprivation
Study type: Interventional

Summary: 
      The goal of this proposed research is to test the hypothesis that long-term mild sleep
      restriction (SR), as occurs frequently in adults and adolescents, leads to a positive energy
      balance and weight gain.

      Aim 1. To determine the effects of SR, relative to habitual sleep (HS), on food choice and
      energy intake (EI) in adults at risk of obesity.

        -  Hypothesis 1a. EI, assessed by multiple weekly 24-hour recalls, will be greater during a
           period of SR relative to HS. This will be mostly due to increased fat and carbohydrate
           intakes.

        -  Hypothesis 1b. Neuronal responses to food stimuli, assessed by functional MRI (fMRI)
           after 6 weeks of SR or HS, will indicate increased activity in networks associated with
           reward and food valuation (insula, orbitofrontal cortex) during a period of SR relative
           to HS. These responses will be correlated with intakes of high carbohydrate and high fat
           foods (hypothesis 1a) and neuropeptide Y (NPY). Moreover, activation of the default mode
           network (DMN) will be suppressed to a lesser extent after SR compared to HS.

      Aim 2. To determine the effects of SR, relative to HS, on energy expenditure (EE) via
      independent and complementary approaches.

        -  Hypothesis 2a. EE, assessed by doubly-labeled water (DLW), and physical activity level,
           monitored daily by actigraphy, will be lower during SR relative to HS.

        -  Hypothesis 2b. Brown adipose tissue (BAT), assessed by positron emission tomography and
           magnetic resonance combined scanner (PET/MR) using 18F-fluorodeoxyglucose (18FDG-PET)
           and fat fraction (FF) measurement under cold stimulation, will be greater after SR
           relative to HS. This would suggest higher adaptive thermogenesis after SR compared to
           HS. BAT activation will also be correlated with NPY.

      Aim 3. To determine whether SR alters body weight and adiposity relative to HS.

        -  Hypothesis 3a. SR will lead to weight gain and increased total adiposity, as assessed
           using magnetic resonance imaging (MRI), relative to HS.

        -  Hypothesis 3b. Increased adiposity after SR will be correlated to an adverse
           cardio-metabolic risk profile (increased glucose, insulin, triglycerides, leptin,
           reduced high-density lipoprotein cholesterol and adiponectin) and neuronal responses to
           food stimuli (Hypothesis 1b), and EE (Hypothesis 2a & 2b). Failure to stimulate BAT with
           SR will be associated with greater gain in adiposity.
    

Detailed description: 
      There is an association between short sleep duration (SSD) and obesity. Moreover, short
      sleepers (<7 hours sleep/night) gain more weight over time than normal sleepers (7-8 hours
      sleep/night). These relationships are increasingly supported by clinical data showing that
      restricting sleep duration in healthy, normal weight adults, increases energy intake (EI).
    

Intervention name(s): Partial Sleep Restriction; Total Sleep Deprivation; Habitual Sleep
Intervention type(s): Behavioral; Behavioral; Behavioral
Intervention description(s): 4 hour time in bed (TIB), participants will go to bed 4 hours later than during the HS condition. Wake-up times will be the same. During the in-lab portion of the PSR, meals, fulfilling weight-maintenance energy requirements, will be supplied by the research staff as BOOST shakes.; 0 hour time in bed (TIB), participants will remain awake throughout the night. Meals will be provided as BOOST shakes at the same meal.; 8 hours time in bed (TIB), for 3 nights, with fixed bed and wake times, while at home. During the 3-d HS phase, participants will be provided will BOOST meal replacement shakes in amounts required to achieve weight maintenance.
Other intervention name(s): PSR; TSD; HS
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: sleep restriction; obesity; brown adipose tissue