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A Human Thrifty Phenotype Associated With Less Weight Loss During Caloric Restriction.

ABSTRACT: Successful weight loss is variable for reasons not fully elucidated. Whether effective weight loss results from smaller reductions in energy expenditure during caloric restriction is not known. We analyzed whether obese individuals with a "thrifty" phenotype, that is, greater reductions in 24-h energy expenditure during fasting and smaller increases with overfeeding, lose less weight during caloric restriction than those with a "spendthrift" phenotype. During a weight-maintaining period, 24-h energy expenditure responses to fasting and 200% overfeeding were measured in a whole-room indirect calorimeter. Volunteers then underwent 6 weeks of 50% caloric restriction. We calculated the daily energy deficit (kilocalories per day) during caloric restriction, incorporating energy intake and waste, energy expenditure, and daily activity. We found that a smaller reduction in 24-h energy expenditure during fasting and a larger response to overfeeding predicted more weight loss over 6 weeks, even after accounting for age, sex, race, and baseline weight, as well as a greater rate of energy deficit accumulation. The success of dietary weight loss efforts is influenced by the energy expenditure response to caloric restriction. Greater decreases in energy expenditure during caloric restriction predict less weight loss, indicating the presence of thrifty and spendthrift phenotypes in obese humans.

SUBMITTER: Reinhardt M

PROVIDER: S-EPMC4512223 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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A Human Thrifty Phenotype Associated With Less Weight Loss During Caloric Restriction.

Reinhardt Martin M Thearle Marie S MS Ibrahim Mostafa M Hohenadel Maximilian G MG Bogardus Clifton C Krakoff Jonathan J Votruba Susanne B SB

Diabetes 20150511 8

Successful weight loss is variable for reasons not fully elucidated. Whether effective weight loss results from smaller reductions in energy expenditure during caloric restriction is not known. We analyzed whether obese individuals with a "thrifty" phenotype, that is, greater reductions in 24-h energy expenditure during fasting and smaller increases with overfeeding, lose less weight during caloric restriction than those with a "spendthrift" phenotype. During a weight-maintaining period, 24-h en ...[more]

PMID: 25964395

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Project description:BackgroundMetabolic and behavioral adaptations to caloric restriction (CR) in free-living conditions have not yet been objectively measured.Methodology and principal findingsForty-eight (36.8+/-1.0 y), overweight (BMI 27.8+/-0.7 kg/m(2)) participants were randomized to four groups for 6-months;Controlenergy intake at 100% of energy requirements; CR: 25% calorie restriction; CR+EX: 12.5% CR plus 12.5% increase in energy expenditure by structured exercise; LCD: low calorie diet (890 kcal/d) until 15% weight reduction followed by weight maintenance. Body composition (DXA) and total daily energy expenditure (TDEE) over 14-days by doubly labeled water (DLW) and activity related energy activity (AREE) were measured after 3 (M3) and 6 (M6) months of intervention. Weight changes at M6 were -1.0+/-1.1% (CONTROL), -10.4+/-0.9% (CR), -10.0+/-0.8% (CR+EX) and -13.9+/-0.8% (LCD). At M3, absolute TDEE was significantly reduced in CR (-454+/-76 kcal/d) and LCD (-633+/-66 kcal/d) but not in CR+EX or controls. At M6 the reduction in TDEE remained lower than baseline in CR (-316+/-118 kcal/d) and LCD (-389+/-124 kcal/d) but reached significance only when CR and LCD were combined (-351+/-83 kcal/d). In response to caloric restriction (CR/LCD combined), TDEE adjusted for body composition, was significantly lower by -431+/-51 and -240+/-83 kcal/d at M3 and M6, respectively, indicating a metabolic adaptation. Likewise, physical activity (TDEE adjusted for sleeping metabolic rate) was significantly reduced from baseline at both time points. For control and CR+EX, adjusted TDEE (body composition or sleeping metabolic rate) was not changed at either M3 or M6.ConclusionsFor the first time we show that in free-living conditions, CR results in a metabolic adaptation and a behavioral adaptation with decreased physical activity levels. These data also suggest potential mechanisms by which CR causes large inter-individual variability in the rates of weight loss and how exercise may influence weight loss and weight loss maintenance.Trial registrationClinicalTrials.gov NCT00099151.

Project description:BackgroundAdaptive thermogenesis during prolonged energy deficit refers to the greater than expected reduction in energy expenditure (EE) independent of concomitant loss of metabolically active body mass.ObjectiveAs inter-individual variability in the magnitude of adaptive thermogenesis may influence the extent of energy deficit thereby predicting the amount of weight reduction, we investigated whether early adaptive thermogenesis is a determinant of weight loss after 6 weeks of daily 50% caloric restriction in an inpatient setting.Design and methodsThe current study reports the results of an exploratory, secondary analysis in overweight but otherwise healthy subjects (n = 11, 7 men, 35 ± 9y, BMI = 40 ± 7 kg/m2, body fat = 63.3 ± 5.3%). Body composition and 24-h EE (24hEE) measurement in a whole-room indirect calorimeter were used to calculate the magnitude of adaptive thermogenesis while on caloric restriction after 1, 3 and 6 weeks. Energy deficit during caloric restriction was quantified via food, stool, and urine bomb calorimetry. Fasting hormonal concentrations (FT4, FT3, FGF21, leptin) were obtained at baseline and at weeks 3 and 6 during caloric restriction.ResultsThe magnitude of adaptive thermogenesis in 24hEE after 1 week of caloric restriction was -178 ± 137 kcal/day (mean ± SD), was overall stable during and following caloric restriction, and demonstrated remarkable intra-individual consistency. A relatively greater decrease in 24hEE of 100 kcal/d after 1 week of caloric restriction was associated on average with reduced energy deficit by 8195 kcal over 6 weeks and predicted 2.0 kg less weight loss, of which 0.5 kg was fat mass, after 6 weeks. No correlations were found between hormonal concentrations and weight loss.ConclusionsThe extent of weight loss is influenced by the magnitude of adaptive thermogenesis in the early stage of caloric restriction. Although these results need replication in larger study groups with adequate statistical power, targeting adaptive thermogenesis may help to optimize long-term interventions in obesity therapy.

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A Human Thrifty Phenotype Associated With Less Weight Loss During Caloric Restriction.

Publications

A Human Thrifty Phenotype Associated With Less Weight Loss During Caloric Restriction.

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