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.

Trial registration: ClinicalTrials.gov NCT00687115.

Figure 1

Illustration of the concept of spendthrift and thrifty phenotypes, characterized by their individual 24h-EE response to overfeeding and fasting.

Figure 2

Study design. Bomb refers to the bomb calorimetry of intake (food) and output (urine and feces). CR, 24h-EE assessment during caloric restriction; EB 1, 24h-EE assessment to determine weight-maintaining energy needs; EB 2, 24h-EE assessment in energy balance; EB 3, 24h-EE assessment in energy balance at new weight; FST, 24h-EE assessment during fasting; OF, 24h-EE assessment during overfeeding chamber; OGTT, oral glucose tolerance test; **At least 48 h at 100% WMD between the two 24h-EE assessments.

Figure 3

A: Individual percent weight loss curves. Baseline weight (Day 0) was set as the weight from the initial DXA scan during the weight stabilization period, and final weight was from the last day of CR (Day 42). Weight increases in 3 individuals between Day 0 and Day 1 are due to weight variations during the stabilization period. C, Caucasian; H, Hispanic; NA, Native American. B: Correlation between 24h-EE response to fasting and percent weight change during CR (r = −0.84; P ≤ 0.001; n = 12). C: Correlation between percent sedentary time during CR and percent weight loss (r = 0.63; P = 0.04; n = 11). ○, Female volunteer; ▲, male volunteer.

Figure 4

A: Correlation between summed calculated energy deficit over 42 days and percent weight loss during CR (r = 0.7; P = 0.02; n = 11). B: Daily cumulative (42 days) calculated energy deficit by categorization of thrifty (gray line) and spendthrift (black line) phenotypes, based on the median of 24h-EE response to fasting; thrifty phenotype n = 6; spendthrift phenotype n = 5. Error bars represent standard deviations. C: Correlation between percent decrease in 24h-EE in response to fasting and summed calculated energy deficit over 42 days (r = −0.66; P = 0.03; n = 11). D: Daily cumulative calculated energy deficit over 42 days with assumed energy deficit data points superimposed. The upper and lower dashed lines represent the 95% CI of the means of the calculated energy deficit. Vertical error bars associated to the closed squares represent the standard deviation of the assumed energy deficit. ○, Female volunteer; ▲, male volunteer.