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.
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.
12-wk weight loss intervention using a meal replacement strategy (Health \& Nutrition Technology, Carmel, CA), with an 8-10% weight loss goal
16-wk supervised endurance exercise training program
3-day hypercaloric diet designed to overfeed by 40% above total daily energy requirements
University of Colorado Hospital
Aurora, Colorado, United States
RECRUITINGFat oxidation as a correlate of weight regain as measured by room calorimetry
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.
Time frame: 24 hour period on day 7 of two diet conditions - one overfed & one eucaloric condition; weeks 16 & 20
Body weight per scale
Body weight will be measured via clinic scale. Change in body weight in response to the weight loss intervention
Time frame: Baseline, after 12 week weight loss intervention and 1 year after the end of second study condition
Body Composition via DXA
Body composition will be measured via DXA, Change in body composition in response to the weight loss intervention
Time frame: Baseline, after 12 week weight loss intervention and 1 year after the end of second study condition
Change in substrate utilization as measured by room calorimetry
Substrate utilization will be measured by room calorimetry (change = overfeeding diet condition - eucaloric diet condition)
Time frame: 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
Change in nocturnal lipolysis as measured by use of stable isotope tracer
Lipolysis will be measured using stable isotope tracers (change = overfeeding diet condition - eucaloric diet condition)
Time frame: 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
Change in total energy expenditure (TEE) as measured by room calorimetry
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Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
75
TEE will be measured by room calorimetry (change = overfeeding diet condition - eucaloric diet condition)
Time frame: 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
Change in spontaneous physical activity (SPA) as measured by accelerometers
SPA will be measured using accelerometers (change = overfeeding diet condition - eucaloric diet condition)
Time frame: 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
Change in spontaneous food intake measured with an ad libitum diet
Spontaneous food intake will be measured during a 3 day ad libitum diet (change = overfeeding diet condition - eucaloric diet condition)
Time frame: 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
Change in hunger and satiety using Visual Analog Scale
Hunger and satiety will be measured using visual analog scales (change = overfeeding diet condition - eucaloric diet condition)
Time frame: 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
Change in 24h hormone and metabolite profiles as measured by assay of plasma samples
24h hormone and metabolite profiles will be assayed in plasma samples obtained during inpatient study visits (change = overfeeding diet condition - eucaloric diet condition)
Time frame: 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
Lipolysis as a correlate of weight regain as measured by stable isotope tracer
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.
Time frame: 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
Total energy expenditure (TEE) as a correlate of weight regain as measured by room calorimetry
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.
Time frame: 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
Spontaneous physical activity (SPA) as a correlate of weight regain as measured by accelerometers
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.
Time frame: 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
Spontaneous food intake as a correlate of weight regain as measured with an ad libitum diet
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.
Time frame: 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 as a correlate of weight regain as measured by assay of plasma samples
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.
Time frame: 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
Total daily energy expenditure as a correlate of weight regain as measured by doubly labeled water
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
Time frame: 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
Correlates of Weight Regain as measured by questionnaire
Correlates of weight regain will be assessed in both reduced obese groups with questionnaires periodically over the intervention and follow-up period
Time frame: 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.