Background

Metabolically “thrifty” individuals are more susceptible to gain weight and more resistant to lose weight compared to individuals with a more spendthrift phenotype. Thrifty individuals show a greater decrease in 24h energy expenditure (24EE) from energy balance (ENBAL) to fasting conditions compared to spendthrift subjects. The hormonal mediators underlying the decrease in 24EE from ENBAL to fasting have not been fully identified.

Methods

In 108 healthy subjects, 24EE was measured in a whole-room indirect calorimeter both during ENBAL and fasting conditions and adjusted for body composition (measured by DXA) and other known 24EE determinants via linear regression. Subjects were categorized as thrifty or spendthrift based on the median value (−161 kcal/day) of the difference in adjusted 24EE between ENBAL and fasting. Concomitant 24h urinary epinephrine and norepinephrine (n=88) were assessed by liquid chromatography–mass spectrometry, while leptin (n=51) was measured before and after the 24h fast by ELISA.

Results

Compared to ENBAL, adjusted 24EE decreased on average by 172 kcal/day (SD=93, range −470 to 122) during 24h fasting. A greater-than median 24EE decrease during fasting (thriftier phenotype) was due to a higher 24EE during ENBAL (+124 kcal/day, 95% confidence interval [CI] 77, 171, p<0.0001) but not to a lower 24EE during fasting which was instead similar between both groups (p=0.35). After 24h fasting, leptin decreased by 9.3 pg/mL (CI −11.1, −5.6), epinephrine increased by 1.6 µg/24h (CI 1.0, 2.2) and norepinephrine decreased by 4.9 µg/24h (CI −7.4, −2.4). A greater decrease in leptin (r=0.28, p=0.04) and less increase in epinephrine (r=0.24 , p=0.03) were independently associated with a greater decrease in adjusted 24EE during fasting.

Conclusions

In metabolically thrifty subjects, the greater decrease in 24EE during fasting is a result of higher EE requirements during eucaloric conditions and is mediated via a leptin and epinephrine response to feeding.