Adaptive Responses to Overfeeding and Weight
- Conditions
- Obesity
- Interventions
- Other: Weight LossOther: OverfeedingOther: Exercise training
- Registration Number
- NCT03857048
- Lead Sponsor
- University of Colorado, Denver
- Brief Summary
To more effectively address the problem of weight regain following weight loss for obese individuals, this study will evaluate the underlying biology of the reduced obese state. In depth studies of appetite, energy expenditure, physical activity levels and fat metabolism will be completed in obese and reduced obese individuals; with the latter subdivided into those who have lost weight with diet alone or diet plus exercise. Individuals will be studied following a brief overfeeding period to better understand how differences in biological responses to overeating might be involved in promoting or protecting against weight gain.
- Detailed Description
The persistent problem of weight regain following weight loss is perhaps the most significant barrier to addressing the current obesity epidemic. The biological drive to regain weight following weight loss is due in part to increased appetite leading to increased energy intake (EI) and reductions in energy expenditure (EE) in part due to changes in energy expended in physical activity (PA). These physiological adaptations to weight loss are most relevant during episodes of dietary indiscretion resulting in overfeeding (OF) when reduced obese (RO) people fail to respond to the state of positive energy balance in a way that maintains the reduced state. There is increasing evidence that RO individuals who exercise (RO-Ex) are less like to regain as compared to RO individuals who are sedentary (RO-Sed). Previous studies were conducted on the effects of OF on EI, EE, PA and fat metabolism in non-obese individuals either prone (OP) or resistant to obesity (OR). Subjects were then followed for 5 years to measure weight change. These studies showed that differences in the response of nocturnal fat oxidation and higher levels of moderate/vigorous PA following OF correlated with 5 year weight gain suggesting that these factors were potentially important mechanisms for weight gain. Previous work has shown that measures of hunger fail to suppress with OF in RO individuals and that nocturnal fat oxidation is reduced in RO-Sed but maintained in RO-Ex following a day that included a bout of exercise. This study will look at the responses of EE, EI, PA and fat metabolism to OF (40% above basal energy for 3 days) in obese, RO-Sed and RO-Ex men and women and correlate these responses to weight change over the subsequent year. The hypothesis is that changes in the response of one or more of these variables to OF will correlate with weight regain. The Significance of the studies lies in the fact that subjects will begin to clarify the metabolic mechanisms that underlie a propensity for weight regain in RO individuals. Innovation: The proposed studies will systematically examine a range of responses to OF and prospectively correlate them with weight gain while taking into account aspects of behavior relevant to weight regain. The hope is that these studies will lay a foundation for future studies that will examine the mechanisms underlying specific adaptive responses that directly relate to weight regain and help with the design of strategies to address and/or respond to these processes.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 75
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Reduced obese + diet group Weight Loss Persons with obesity randomized to a weight loss program consisting of caloric restriction and behavioral support. Following weight loss persons in this group will participate in an inpatient assessment to measure metabolic responses to a 3 day eucaloric diet or a 3 day overfeeding challenge. Participants will be followed for 1 year after the metabolic studies to track longitudinal changes in body weight and other relevant health outcomes. Control Overfeeding Persons with obesity who do not undergo weight loss will participate in an inpatient assessment to measure metabolic responses to a 3 day eucaloric diet or a 3 day overfeeding challenge. Participants will be followed for 1 year after the metabolic studies to track longitudinal changes in body weight and other relevant health outcomes. Reduced obese + diet + exercise Exercise training Persons with obesity randomized to a weight loss program consisting of caloric restriction, behavioral support, and supervised endurance exercise training. Following weight loss persons in this group will participate in an inpatient assessment to measure metabolic responses to a 3 day eucaloric diet or a 3 day overfeeding challenge. Participants will be followed for 1 year after the metabolic studies to track longitudinal changes in body weight and other relevant health outcomes. Reduced obese + diet + exercise Weight Loss Persons with obesity randomized to a weight loss program consisting of caloric restriction, behavioral support, and supervised endurance exercise training. Following weight loss persons in this group will participate in an inpatient assessment to measure metabolic responses to a 3 day eucaloric diet or a 3 day overfeeding challenge. Participants will be followed for 1 year after the metabolic studies to track longitudinal changes in body weight and other relevant health outcomes. Reduced obese + diet + exercise Overfeeding Persons with obesity randomized to a weight loss program consisting of caloric restriction, behavioral support, and supervised endurance exercise training. Following weight loss persons in this group will participate in an inpatient assessment to measure metabolic responses to a 3 day eucaloric diet or a 3 day overfeeding challenge. Participants will be followed for 1 year after the metabolic studies to track longitudinal changes in body weight and other relevant health outcomes. Reduced obese + diet group Overfeeding Persons with obesity randomized to a weight loss program consisting of caloric restriction and behavioral support. Following weight loss persons in this group will participate in an inpatient assessment to measure metabolic responses to a 3 day eucaloric diet or a 3 day overfeeding challenge. Participants will be followed for 1 year after the metabolic studies to track longitudinal changes in body weight and other relevant health outcomes.
- Primary Outcome Measures
Name Time Method Fat oxidation as a correlate of weight regain as measured by room calorimetry 24 hour period on day 7 of two diet conditions - one overfed & one eucaloric condition; weeks 16 & 20 Fat oxidation as a correlate of weight regain will be assessed in both reduced obese groups with room calorimetry on two occasions, once after 3 days of overfeeding and once after 3 days of an energy balanced diet.
- Secondary Outcome Measures
Name Time Method Change in nocturnal lipolysis as measured by use of stable isotope tracer 24 hour period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced Lipolysis will be measured using stable isotope tracers (change = overfeeding diet condition - eucaloric diet condition)
Change in total energy expenditure (TEE) as measured by room calorimetry 24 hour period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced TEE will be measured by room calorimetry (change = overfeeding diet condition - eucaloric diet condition)
Body weight per scale Baseline, after 12 week weight loss intervention and 1 year after the end of second study condition Body weight will be measured via clinic scale. Change in body weight in response to the weight loss intervention
Body Composition via DXA Baseline, after 12 week weight loss intervention and 1 year after the end of second study condition Body composition will be measured via DXA, Change in body composition in response to the weight loss intervention
Change in spontaneous physical activity (SPA) as measured by accelerometers 7 days, on days 4-10 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced SPA will be measured using accelerometers (change = overfeeding diet condition - eucaloric diet condition)
Change in spontaneous food intake measured with an ad libitum diet 3 days - on days 8-10 - of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced Spontaneous food intake will be measured during a 3 day ad libitum diet (change = overfeeding diet condition - eucaloric diet condition)
Lipolysis as a correlate of weight regain as measured by stable isotope tracer 24 period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced Lipolysis as a correlate of weight regain will be assessed in both reduced obese groups with a stable isotope tracer on two occasions, once after 3 days of overfeeding and once after 3 days of an energy balanced diet.
Total energy expenditure (TEE) as a correlate of weight regain as measured by room calorimetry 24 period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced TEE as a correlate of weight regain will be assessed in both reduced obese groups with room calorimetry on two occasions, once after 3 days of overfeeding and once after 3 days of an energy balanced diet.
24h hormone and metabolite profiles as a correlate of weight regain as measured by assay of plasma samples 24 period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced 24h hormone and metabolite profiles as a correlate of weight regain will be assessed in both reduced obese groups by assay of plasma samples on two occasions, once after 3 days of overfeeding and once after 3 days of an energy balanced diet.
Change in substrate utilization as measured by room calorimetry 24 hour period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and week 16 & 20 for reduced groups Substrate utilization will be measured by room calorimetry (change = overfeeding diet condition - eucaloric diet condition)
Change in 24h hormone and metabolite profiles as measured by assay of plasma samples 3 days - days 8-10 - of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced 24h hormone and metabolite profiles will be assayed in plasma samples obtained during inpatient study visits (change = overfeeding diet condition - eucaloric diet condition)
Spontaneous food intake as a correlate of weight regain as measured with an ad libitum diet 3 days - days 8-10 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced SPA as a correlate of weight regain will be assessed in both reduced obese groups with an ad libitum diet on two occasions, once after 3 days of overfeeding and once after 3 days of an energy balanced diet.
Change in hunger and satiety using Visual Analog Scale 3 days - on days 8-10 - of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced Hunger and satiety will be measured using visual analog scales (change = overfeeding diet condition - eucaloric diet condition)
Spontaneous physical activity (SPA) as a correlate of weight regain as measured by accelerometers 7 days, on days 4-10 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced SPA as a correlate of weight regain will be assessed in both reduced obese groups with accelerometers on two occasions, once after 3 days of overfeeding and once after 3 days of an energy balanced diet.
Total daily energy expenditure as a correlate of weight regain as measured by doubly labeled water two 1 week periods at 1 month and 1 year after second diet condition; week 8 and week 56 for controls and week 24 and week 72 for reduced Total daily energy expenditure as a correlate of weight regain will be measured in both reduced obese groups using doubly labeled water after the second diet condition intervention
Correlates of Weight Regain as measured by questionnaire 30 minutes at baseline and every 8 weeks for 1 year following second diet condition; weeks 12, 20, 28, 36, 44, 52 for controls and weeks 28, 36, 44, 52, 60, 68, for reduced. Correlates of weight regain will be assessed in both reduced obese groups with questionnaires periodically over the intervention and follow-up period
Trial Locations
- Locations (1)
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States