Obesity remains a public health epidemic despite substantial advances in treatment strategies and therapies in the last decade. Effective strategies to support maintenance of improved metabolic health and reduced body weight are still needed. Signals from the gut to the brain are important in regulating metabolism and energy balance and have been linked with food reward and preference in metabolically healthy individuals with normal body mass index. In particular, post-ingestive signaling related to glucose metabolism has been linked with food reward and preference. However, not much is known about how these gut and brain signals interact to influence eating behaviors in states of obesity or altered metabolic health. In addition, evidence in rodent models and human studies indicates obesity is associated with a blunted brain response to foods compared with normal body weight. However, whether altered nutrient utilization, termed metabolic inflexibility, influences the relationship between obesity and food reward has yet to be studied. The overall objective of this proof-of-concept pilot study is to assess the feasibility of measuring reward response following a flavor-nutrient conditioning paradigm across the normal to obese body mass index (BMI) range and in states of altered metabolic health. The aims of this study are: 1) to determine whether differences in reinforcement learning/flavor-nutrient conditioning of carbohydrate can be measured across the body mass index range; and 2) to determine the feasibility of assessing metabolic flexibility and whether a relationship between metabolic flexibility and calorie-predictive reward can be detected.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
SINGLE
Enrollment
20
Participants will consume flavored beverage solutions containing 75 calories of sucrose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws over a 2-hour period, and one exposure session will include indirect calorimetry measurement pre- and post-consumption. The other 4 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.
Participants will consume flavored beverage solutions sweetened with sucralose to match the sweetness of 75 calories of sucrose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws over a 2-hour period, and one exposure session will include indirect calorimetry measurement pre- and post-consumption. The other 4 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.
A high-fat test meal (60% fat, 20% carbohydrate) will be provided after a 1-hour baseline measurement of substrate oxidation during a 6-hour metabolic chamber stay. Postprandial substrate oxidation will be measured for 5 hours.
A high-carbohydrate test meal (60% carbohydrate, 20% fat) will be provided after a 1-hour baseline measurement of substrate oxidation during a 6-hour metabolic chamber stay. Postprandial substrate oxidation will be measured for 5 hours.
A subset of participants with BMI \> 25 will be invited to complete an functional magnetic resonance imaging (fMRI) scan as a feasibility measure. fMRI scans will be performed while beverages (without calories) used during the intervention are delivered through a custom manifold fitted to a head coil and connected to a pump system that allows precisely timed and measured delivery of liquids. Because this is feasibility-based measure, the outcome is a count of participants who completed this task.
Fralin Biomedical Research Institute at Virginia Tech Carilion
Roanoke, Virginia, United States
Change in Preference- Liking
Subjective ratings of liking of flavors used in the intervention were assessed at baseline and after the intervention. The generalized Labeled Magnitude Scale will be used. The scale is anchored by descriptors of "Most Disliked Sensation Imaginable" and "Most Liked Sensation Imaginable" at the lower and upper ends, respectively. The score is determined by the place on the scale participants select (range of scale is 0-100). An increase in score from baseline to post-intervention indicates an increase in liking.
Time frame: Baseline and at 4 weeks
Post-test Preference - Wanting
Subjective ratings of wanting of flavors used in the intervention will be assessed at baseline and after the intervention. A Visual Analog Scale will be used. Participants select a place on the line that corresponds with their subjective rating, and the score is determined by the place selected (range of scores is 0-100). The line is anchored by polar opposite descriptors ("Do not want at all" and "Want very much"). An increase in score from baseline to post-intervention indicates and increase in wanting.
Time frame: Baseline and at 4 weeks
Change in Preference- Wanting
Ad libitum intake will be used as a measure of wanting in a post-test session. Participants will be provided each beverage used during the intervention and asked to drink as much or as little of them as they would like over a 30-minute period. Total beverage intake over 30 minutes is reported as the outcome.
Time frame: 30-minute measurement
Change in Preference- Wanting
Forced choice will be used as a measure of wanting in a post-test session. Participants will be provided each of the beverages used during the intervention and asked to choose 1 to take home with them. The outcome variable is a count of number of participants who chose each beverage condition during the forced choice test.
Time frame: 5-minute measurement
Blood Oxygen Level-dependent (BOLD) Response to Beverages
In a post-test session, functional magnetic resonance imaging (fMRI) scans were performed while beverages (without calories) used during the intervention and a tasteless solution are delivered through a custom manifold fitted to a head coil and connected to a pump system that allows precisely timed and measured delivery of liquids. Only participants with BMI \> 25 were invited to complete this portion of the study, per our protocol. In total, participants receive the CS+, CS-, and tasteless (control) solutions 24 times over the course of 2 runs. Contrasts of interest are the blood oxygen level-dependent (BOLD) response of CS+\>tasteless solution and CS-\>tasteless solution deliveries. Parameter estimates for these contrasts are extracted and reported. A positive outcome reflects greater whole-brain BOLD response for the CS condition compared with a tasteless solution.
Time frame: 30-minute measurement that occurs during the post-test, approximately 4 weeks after the first study session
Substrate Oxidation Response to Test Meals
Indirect calorimetry in a metabolic chamber will be used to assess substrate oxidation response to high-fat and high-carbohydrate test meals.
Time frame: 6-hour measurement
Blood Glucose Response to Beverages
Blood glucose will be assessed at baseline and at set time points for 1 hour after consumption of intervention beverages in one exposure session.
Time frame: 2-hour measurement
Blood Insulin Response to Beverages
Blood insulin will be assessed at baseline and at set time points for 2 hours after consumption of intervention beverages in an exposure session.
Time frame: 2-hour measurement
Energy Expenditure in Response to Beverages
Indirect calorimetry will be used to determine energy expenditure at baseline (for 30 minutes) and for 1 hour after consumption of intervention beverages in an exposure session.
Time frame: 1.5-hour measurement
Respiratory Exchange Ratio in Response to Beverages
Indirect calorimetry will be used to determine respiratory exchange ratio (RER) at baseline (for 30 minutes) and for 1 hour after consumption of intervention beverages in an exposure session. Areas under the curve for change in RER were calculated for each condition and presented as outcomes.
Time frame: 1.5-hour measurement
Substrate Oxidation in Response to Beverages
Indirect calorimetry will be used to determine substrate oxidation at baseline (for 30 minutes) and for 1 hour after consumption of intervention beverages in an exposure session.
Time frame: 1.5-hour measurement
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